CN115584518A - Electrochemical method for preparing N-alkylamide - Google Patents
Electrochemical method for preparing N-alkylamide Download PDFInfo
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- CN115584518A CN115584518A CN202211306652.9A CN202211306652A CN115584518A CN 115584518 A CN115584518 A CN 115584518A CN 202211306652 A CN202211306652 A CN 202211306652A CN 115584518 A CN115584518 A CN 115584518A
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Abstract
An electrochemical process for the preparation of an N-alkylamide comprising the steps of: in an air atmosphere, adding a fatty amine compound and alpha-keto acid into a reactor at a molar ratio of 1.2, adding an electrolyte of tetrabutylammonium fluoride, and adding dichloromethane and tetrahydrofuran 4: 1; stirring the mixture by a magnetic stirring device to dissolve the mixture, inserting two electrodes, electrifying for 2h by using a graphite electrode as a positive electrode and a platinum sheet electrode as a negative electrode for 8mA, evaporating the solvent under reduced pressure after the reaction is finished to obtain a crude product, and purifying by column chromatography to obtain the N-alkyl amide 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 current is used as an oxidation method in the reaction, so that the pollution of transition metal or chemical oxidant is avoided; easily available raw materials, 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 N-alkylamide.
Background
Amide structure is one of the most basic chemical building blocks found in nature. It constitutes the backbone of biologically important proteins and is present in a large number of synthetic structures (Science 2020,367, 281-285.). Since the interest in polypeptides, i.e., important amide-containing biopolymers in biological organisms, has increased rapidly, methods for efficiently constructing amide bonds have been extensively studied and are one of the most fundamental and important transformations in organic synthesis. Therefore, the synthesis of the N-alkylamide compound has important application and research values.
The methods for synthesizing amide compounds that have been reported so far are mainly carboxylic acid and amine based dehydration condensation reactions that use equivalent amounts of chemical oxidizing agents or condensing agents to promote the reaction. In recent years, electrochemical synthesis has received increasing attention because it avoids the use of catalysts and external oxidants, meeting the requirements of green and sustainable chemistry.
Disclosure of Invention
Aiming at the problems, the invention provides an electrochemical method for preparing N-alkylamide, 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 transition metal and 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 method for preparing N-alkyl sulfoxide imide, which comprises the following steps:
in an air atmosphere, a fatty amine compound and an alpha-keto acid are added into a reactor at a molar ratio of 1.2, an electrolyte of tetrabutylammonium fluoride is added, and dichloromethane and tetrahydrofuran 4: 1; stirring the mixture by a magnetic stirring device to dissolve the mixture, inserting two electrodes, electrifying the positive electrode by a graphite electrode and the negative electrode by a platinum sheet electrode for 8mA for 2h, evaporating the solvent under reduced pressure after the reaction is finished to obtain a crude product, and purifying by column chromatography to obtain the N-alkyl amide compound.
In the step, the reactor is a diaphragm-free electrolytic cell, and the N-alkyl amide compound is prepared through electrochemical reaction, wherein the preparation method comprises the following reaction formula:
in the formula R 1 = benzyl, each substituted alkyl; r 2 = phenyl, substituted phenyl, eachA substituted aromatic heterocyclic compound; the electrolyte is tetrabutylammonium fluoride.
Preferably, the anode electrode plate is a carbon rod electrode, and the cathode electrode plate is a platinum plate electrode.
Preferably, the electrolyte is tetrabutylammonium fluoride with a concentration of 0.05mol/L.
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 8 milliamperes.
Preferably, the solvent is a mixed solvent of dichloromethane and tetrahydrofuran, and the ratio of dichloromethane to tetrahydrofuran is 4.
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 3.
The invention has the beneficial effects that:
1. the invention adopts cheap and easily obtained alpha-keto acid and fatty amine as raw materials, the alpha-keto acid can be prepared from corresponding acetophenone, and the fatty amine is obtained by a commercial way.
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 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 carbon spectrum of the 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 chart showing a carbon spectrum of a 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 chart showing a carbon spectrum of a 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 based on the embodiments described herein are intended to be within the scope of the present invention.
Example 1:
a10 mL diaphragm-free electrolytic cell was equipped with a carbon rod electrode (electrode size: diameter. Phi.6 mm) as an anode and a platinum sheet (size: 10 mm. Times.10 mm. Times.0.1 mm) as a cathode, followed by addition of benzylamine (21.4 mg, 0.20mmol), benzoylformic acid (36.0mg, 0.24mmol), an electrolyte of tetrabutylammonium fluoride (0.25 mmol), 4mL of dichloromethane, 1mL of tetrahydrofuran, and the reaction was stirred at room temperature for 2 hours at a constant current of 8 mA. 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 35.9mg of a target product, wherein the yield is 85%. 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)δ7.82(d,J＝7.8Hz,2H),7.51(t,J＝7.4 Hz,1H),7.43(t,J＝7.6Hz,2H),7.39-7.29(m,5H),6.66(s,1H),4.65(d,J＝5.7Hz, 2H). 13 C NMR(125MHz,Chloroform-d)δ167.5,138.2,134.4,131.6,128.8,128.6, 127.9,127.6,127.0,44.1.
example 2:
in a 10mL diaphragm-free electrolytic cell equipped with a carbon rod electrode (electrode size: diameter. Phi.6 mm) as an anode and a platinum sheet (size: 10 mm. Times.10 mm. Times.0.1 mm) as a cathode, n-butylamine (14.6 mg, 0.20mmol), benzoylformic acid (36.0mg, 0.24mmol), an electrolyte of tetrabutylammonium fluoride (0.25 mmol), 4mL of dichloromethane, 1mL of tetrahydrofuran, the reaction was stirred at room temperature for 2 hours at a constant current of 8 mA. 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 26.2mg of a target product, wherein the yield is 74%. 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)δ7.78(d,J＝7.6Hz,2H),7.46(t,J＝7.3 Hz,1H),7.39(t,J＝7.6Hz,2H),6.60(s,1H),3.42(q,J＝6.7Hz,2H),1.58(p,J＝ 7.3Hz,2H),1.38(tt,J＝11.0,5.5Hz,2H),0.94(t,J＝7.4Hz,3H). 13 C NMR(125 MHz,Chloroform-d)δ167.7,134.9,131.2,128.5,126.9,39.8,31.7,20.2,13.8.
example 3:
a10 mL diaphragm-free electrolytic cell was equipped with a carbon rod electrode (electrode size: diameter. Phi.6 mm) as an anode and a platinum plate (size: 10 mm. Times.10 mm. Times.0.1 mm) as a cathode, followed by addition of 2-thiophenemethylamine (22.6 mg,0.20 mmol), benzoylformic acid (36.0 mg, 0.24mmol), an electrolyte of tetrabutylammonium fluoride (0.25 mmol), dichloromethane (4 mL), tetrahydrofuran (1 mL), and reaction was stirred at room temperature for 2 hours at a constant current of 8 mA. 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 28.2mg of a target product, wherein the yield is 65%. 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)δ7.80(d,J＝7.6Hz,2H),7.51(t,J＝7.5 Hz,1H),7.42(t,J＝7.6Hz,2H),7.25(d,J＝5.1Hz,1H),7.08-6.90(m,2H),6.80(s, 1H),4.80(d,J＝5.6Hz,2H). 13 C NMR(125MHz,Chloroform-d)δ167.3,140.9, 134.2,131.6,128.6,127.1,127.0,126.2,125.3,38.8.
example 4:
a10 mL diaphragm-free electrolytic cell was equipped with a carbon rod electrode (electrode size: diameter. Phi.6 mm) as an anode and a platinum plate (size: 10 mm. Times.10 mm. Times.0.1 mm) as a cathode, followed by addition of benzylamine (21.4 mg, 0.20mmol), p-bromobenzoyl formic acid (55.0 mg, 0.24mmol), an electrolyte of tetrabutylammonium fluoride (0.25 mmol), dichloromethane (4 mL), tetrahydrofuran (1 mL), and the reaction was stirred at room temperature for 2 hours at a constant current of 8 mA. 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 31.2mg of a target product, wherein the yield is 74%. 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)δ7.72-7.63(m,2H),7.55(dd,J＝8.6,2.1 Hz,2H),7.41-7.29(m,5H),6.63(s,1H),4.62(d,J＝5.7Hz,2H). 13 C NMR(125 MHz,Chloroform-d)δ166.5,138.0,133.2,131.8,128.8,128.6,127.9,127.7,126.3, 44.2.
example 5:
a10 mL diaphragm-free electrolytic cell was equipped with a carbon rod electrode (electrode size: diameter. Phi.6 mm) as an anode and a platinum sheet (size: 10 mm. Times.10 mm. Times.0.1 mm) as a cathode, followed by addition of benzylamine (21.4 mg, 0.20mmol), p-cyanobenzoic acid (42.0mg, 0.24mmol), an electrolyte of tetrabutylammonium fluoride (0.25 mmol), dichloromethane (4 mL), tetrahydrofuran (1 mL), and the reaction was stirred at room temperature for 2 hours at a constant current of 8 mA. 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 25.5mg of a target product, wherein the yield is 54%. 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)δ7.91(d,J＝7.9Hz,2H),7.75(d,J＝7.9 Hz,2H),7.37(hept,J＝7.3Hz,5H),6.51(s,1H),4.67(d,J＝5.6Hz,2H). 13 C NMR (125MHz,Chloroform-d)δ165.6,138.3,137.5,132.5,129.0,128.0,128.0,127.7, 118.0,115.2,44.5。
Claims (6)
1. an electrochemical process for the preparation of an N-alkylamide, characterized in that: the preparation method comprises the following steps: in an air atmosphere, adding a fatty amine compound and alpha-keto acid into a reactor at a molar ratio of 1.2, adding an electrolyte of tetrabutylammonium fluoride, and adding dichloromethane and tetrahydrofuran 4: 1; stirring the mixture by using a magnetic stirring device to dissolve the mixture, inserting two electrodes, electrifying for 2 hours by using a graphite electrode as a positive electrode and a platinum sheet electrode as a negative electrode and electrifying for 8mA, 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 N-alkyl amide compound;
in the step, the reactor is a diaphragm-free electrolytic cell, and the N-alkyl amide compound is prepared through electrochemical reaction, wherein the reaction equation is as follows:
in the formula R 1 = benzyl, each substituted alkyl; r 2 = phenyl group, substituted aromatic heterocyclic compound; the electrolyte is tetrabutylammonium fluoride.
2. An electrochemical process for the preparation of an N-alkylamide according to claim 1, characterized in that: the anode electrode plate is a carbon rod electrode, and the cathode electrode plate is a platinum plate electrode.
3. An electrochemical process for the preparation of an N-alkylamide according to claim 1, characterized in that: the electrolyte is tetrabutylammonium fluoride, and the concentration of the tetrabutylammonium fluoride is 0.05mol/L.
4. An electrochemical process for the preparation of an N-alkyl amide as claimed in 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 8 milliamperes.
5. An electrochemical process for the preparation of an N-alkyl amide as claimed in claim 1, wherein: the solvent is a mixed solvent of dichloromethane and tetrahydrofuran, and the ratio of the dichloromethane to the tetrahydrofuran is 4.
6. An electrochemical process for the preparation of an N-alkylamide 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 3.
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