CN114990590A - Novel method for electrocatalysis metal-free transamidation reaction - Google Patents

Novel method for electrocatalysis metal-free transamidation reaction Download PDF

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CN114990590A
CN114990590A CN202210836038.7A CN202210836038A CN114990590A CN 114990590 A CN114990590 A CN 114990590A CN 202210836038 A CN202210836038 A CN 202210836038A CN 114990590 A CN114990590 A CN 114990590A
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twister
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CN114990590B (en
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王涛
杨凌云
刘升长
姜涛
林海
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Jiangxi Normal University
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    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
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    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
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    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
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Abstract

The invention relates to a novel method for electrocatalysis metal-free transamidation reaction, which takes a platinum electrode as a cathode and an anode of the reaction, an amide twister and tertiary amine as raw materials, n-tetrabutylammonium bromide as an electrolyte, ammonium sulfate as an additive and dichloromethane as a solvent, and synthesizes a tertiary amide product through constant current electrochemical oxidation. Wherein, the mol ratio of the amide twister, the n-tetrabutylammonium bromide, the ammonium sulfate and the tertiary amine is 4: 3: 24. Compared with the traditional method for synthesizing tertiary amide, the method disclosed by the invention does not need transition metal catalysis, directly utilizes electrochemical conditions to promote the reaction, is mild in conditions, simple in operation, high in yield, convenient for separation and purification, green and environment-friendly, and wide in application range of the substrate.

Description

Novel method for electrocatalysis metal-free transamidation reaction
Technical Field
The invention discloses a novel method for electrocatalytic metal-free transamidation reaction, relates to the metal-free transamidation reaction by electrocatalytic oxidation of tertiary amine and amide twister, and particularly belongs to the technical field of organic chemistry.
Technical Field
Tertiary amides and their derivatives are important functional motifs for natural products, pharmaceuticals, pesticides, adhesives and bioactive compounds. Due to the stability and importance of tertiary amides, the development of a simple green sustainable oxidative amidation strategy for the synthesis of tertiary amides is a topic of intense current research. Amides are typically synthesized by the condensation of an amine with a carboxylic acid derivative, but this seems to be a simple reaction process that is difficult to react under mild conditions, usually with increased heat to high temperatures or with the aid of coupling reagents to form the amide. The traditional amide chemical synthesis method is generally completed by activating carboxylic acid by using a coupling reagent and performing condensation reaction between the activated carboxylic acid and amine, or converting the carboxylic acid into acyl chloride or anhydride with higher reactivity and then performing condensation reaction with the amine.
In general, the synthesis of tertiary amides can be achieved by palladium-catalyzed reaction of benzyl or aryl formates or amides with tertiary amines (Xiao-Feng Wu et al, Organic Chemistry Frontiers, 2020,7(21), 3406-. It can also be prepared by the aminocarbonylation of arylboronic acids with non-activated tertiary amines by Pd-catalyzed oxidation via a C-N bond (Bhanage, B.M., et al, Journal of Organic Chemistry, 2021,86(20), 14028-. Although the tertiary amides can be efficiently synthesized by conventional methods, their synthesis mostly requires transition metal catalysis and requires higher temperatures and longer reaction times. The search for a mildly conditioned method for the synthesis of tertiary amides has been a major challenge in current basic organic syntheses.
Disclosure of Invention
The invention aims to provide a green and environment-friendly method for synthesizing tertiary amido bond, so as to overcome the defects of the existing synthesis method.
The invention relates to a novel method for electrocatalysis metal-free transamidation reaction, which takes a platinum electrode as a cathode and an anode of the reaction, takes an amide twister and tertiary amine as raw materials, takes n-tetrabutylammonium bromide as an electrolyte, ammonium sulfate as an additive and dichloromethane as a solvent, and synthesizes a tertiary amide product through constant current electrochemical oxidation;
the method comprises the following specific steps:
step A: adding pre-dried stirring magnetons into the dried Y-pipe, and using platinum sheet electrodes as a cathode and an anode of a reaction; sequentially adding amide twister, n-tetrabutylammonium bromide (0.75equiv) and ammonium sulfate (0.75equiv) into a Y-tube, then respectively adding tertiary amine (6equiv), distilled water (20equiv) and dichloromethane, electrolyzing for 6 hours at constant current under air condition and room temperature, wherein the current is constant at 6mA, and detecting by TLC until the amide twister reaction is complete;
and B: after the reaction is finished, adding a saturated sodium chloride solution into the reaction solution, extracting for three times by using ethyl acetate, drying the combined organic phase by using anhydrous sodium sulfate, and separating and purifying by filtering, spin-drying a solvent and column chromatography to obtain an amide product.
The mol ratio of the amide twister, the n-tetrabutylammonium bromide, the ammonium sulfate and the tertiary amine is 4: 3: 24.
The ratio of the amide twister to the dichloromethane is 1: 50 according to mmol/mL.
The tertiary amine is N-methylpiperidine, trihexylamine, tripentylamine, triisopentylamine or tribenzylamine.
The possible mechanism of the electrocatalytic metal-free transamidation reaction of the invention is as follows:
the triethylamine a is oxidized into radical positive ion b at the anode, then the radical positive ion b and another molecule of triethylamine are subjected to proton exchange to obtain an alpha carbon radical c of N, then an electron is lost to form an imine positive ion intermediate d, and finally the intermediate e is hydrolyzed to obtain a dialkyl amine key intermediate e. Then carrying out simple nucleophilic addition reaction with amide contortion to obtain a tetrahedral intermediate f, and finally decomposing the intermediate f into a target product g.
Figure BDA0003748252800000021
The reaction formula for synthesizing the tertiary amide through electrochemical oxidation of the amide twister and the tertiary amine is as follows:
Figure BDA0003748252800000031
wherein: r 1 Is phenyl, 4-methoxyphenyl or 4-methylphenyl4-phenylphenyl, 2-chlorothienyl, 2, 6-dimethylbenzyl, undecyl, cinnamyl;
R 3 is not equal to R 2 When the tertiary amine is N-methylpiperidine; r 3 Is equal to R 2 When the tertiary amine is trihexylamine, tripentylamine, triisopentylamine, and tribenzylamine.
The invention has the beneficial effects that: compared with the traditional method for synthesizing tertiary amide, the method provided by the invention does not need transition metal catalysis, directly utilizes electrochemical conditions to promote the reaction, is mild in conditions, simple in operation, high in yield, convenient for separation and purification, green and environment-friendly, and wide in substrate application range.
Detailed Description
The following examples 1 to 13 are given to illustrate the advantageous effects of the present invention in detail, and are intended to help the reader to understand the essence of the present invention better, but should not be construed to limit the scope of the present invention in any way.
Example 1
Synthesis of
Figure BDA0003748252800000032
The method comprises the steps of adding a pre-dried stirring magneton into a 25mL oven-dried Y-tube, sequentially adding an amide twister (0.2mmol,40.6mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg) and ammonium sulfate (0.75equiv,19.8mg) into a reaction tube, using a platinum sheet electrode as a cathode and an anode of a reaction, and finally adding triethylamine (6equiv,166uL), distilled water (20equiv,72uL) and dichloromethane (10mL) into a side branch port respectively, carrying out constant current electrolysis for 6 hours at room temperature under an air condition, and detecting by TLC until the amide twister is completely reacted. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 78%, 27.6 mg.
1 H NMR(400MHz,Chloroform-d)δ7.44–7.29(m,5H),3.54(s,2H),3.24(s,2H),1.24(s,3H),1.10(s,3H). 13 C NMR(100MHz,Chloroform-d)δ171.4,137.4,129.2,128.5,126.4,43.4,39.3,14.3,13.0.
Example 2
Synthesis of
Figure BDA0003748252800000041
The oven-dried 25mL of the three-pronged tube was charged with the previously-dried stirring magneton, the amide twister (0.2mmol,46.6mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) were sequentially charged into the reaction tube, the cathode and anode for the reaction were made with platinum sheet electrodes, and finally triethylamine (6equiv,166uL), distilled water (20equiv,72uL) and dichloromethane (10mL) were added to the side branch ports, respectively, and the mixture was electrolyzed at constant current under air conditions at room temperature for 6 hours, and checked by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 78%, 32.3 mg.
1 H NMR(400MHz,Chloroform-d)δ7.33(d,J＝8.4Hz,2H),6.89(d,J＝8.4Hz,2H),3.81(s,3H),3.48(s,2H),3.32(s,2H),1.17(s,6H). 13 C NMR(100MHz,Chloroform-d)δ171.3,160.4,129.6,128.3,113.8,55.4,43.2,39.4,13.9,13.3.
Example 3
Synthesis of
Figure BDA0003748252800000042
The oven-dried 25mL of the three-pronged tube was charged with the previously-dried stirring magneton, the amide twister (0.2mmol,43.4mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) were sequentially charged into the reaction tube, the cathode and anode for the reaction were made with platinum sheet electrodes, and finally triethylamine (6equiv,166uL), distilled water (20equiv,72uL) and dichloromethane (10mL) were added to the side branch ports, respectively, and the mixture was electrolyzed at constant current under air conditions at room temperature for 6 hours, and checked by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 80%, 30.6 mg.
1 H NMR(400MHz,Chloroform-d)δ7.20(d,J＝7.6Hz,2H),7.12(d,J＝7.6Hz,2H),3.46(s,2H),3.20(s,2H),2.30(s,3H),1.16(s,3H),1.04(s,3H). 13 C NMR(100MHz,Chloroform-d)δ171.6,139.2,134.5,129.1,126.5,43.4,39.4,21.5,14.3,13.1.
Example 4
Synthesis of
Figure BDA0003748252800000051
The oven-dried 25mL of the three-pronged tube was charged with the previously-dried stirring magneton, the amide twister (0.2mmol,55.9mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) were sequentially charged into the reaction tube, the cathode and anode for the reaction were made with platinum sheet electrodes, and finally triethylamine (6equiv,166uL), distilled water (20equiv,72uL) and dichloromethane (10mL) were added to the side branch ports, respectively, and the mixture was electrolyzed at constant current under air conditions at room temperature for 6 hours, and checked by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 78%, 39.5 mg.
1 H NMR(400MHz,Chloroform-d)δ7.60(t,J＝8.0Hz,4H),7.44(t,J＝7.2Hz,4H),7.35(t,J＝7.2Hz,1H),3.55(s,2H),3.32(s,2H),1.23(s,3H),1.17(s,3H). 13 C NMR(100MHz,Chloroform-d)δ171.2,142.1,140.4,136.1,128.9,127.7,127.1,127.1,126.9,43.4,39.4,14.2,13.1.
Example 5
Synthesis of
Figure BDA0003748252800000052
The oven-dried 25mL of the three-way tube was charged with the previously-dried stirring magneton, the amide twister (0.2mmol,48.7mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) were sequentially charged into the reaction tube, the cathode and anode for the reaction were made with platinum sheet electrodes, and finally triethylamine (6equiv,166uL), distilled water (20equiv,72uL) and dichloromethane (10mL) were added to the side branch ports, respectively, and the mixture was electrolyzed at constant current for 6 hours under air conditions at room temperature, and checked by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 65%, 28.3 mg.
1 H NMR(400MHz,Chloroform-d)δ7.09(d,J＝4.0Hz,1H),6.83(d,J＝4.0Hz,1H),3.51(q,J＝7.2Hz,4H),1.23(t,J＝7.2Hz,6H). 13 C NMR(100MHz,Chloroform-d)δ162.5,137.3,133.8,127.7,126.1,42.3,13.7.
Example 6
Synthesis of
Figure BDA0003748252800000061
The oven-dried 25mL of the three-way tube was charged with the previously-dried stirring magneton, the amide twister (0.2mmol,49.0mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) were sequentially charged into the reaction tube, the cathode and anode for the reaction were made with platinum sheet electrodes, and finally triethylamine (6equiv,166uL), distilled water (20equiv,72uL) and dichloromethane (10mL) were added to the side branch ports, respectively, and the mixture was electrolyzed at constant current for 6 hours under air conditions at room temperature, and checked by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 50%, 21.9 mg.
1 H NMR(400MHz,Chloroform-d)δ7.05(d,J＝7.6Hz,1H),6.95(d,J＝6.4Hz,2H),3.61(s,2H),3.42(q,J＝7.2Hz,2H),3.28(q,J＝7.2Hz,2H),2.28(s,3H),2.22(s,3H),1.15(q,J＝6.8Hz,6H). 13 C NMR(100MHz,Chloroform-d)δ170.4,135.6,134.1,133.3,130.2,129.7,127.6,77.4,42.4,40.4,38.5,21.1,19.3,14.3,13.1.
Example 7
Synthesis of
Figure BDA0003748252800000062
To 25mL of oven-dried trifurcated tube was added a stirring magneton dried in advance, and then amide twister (0.2mmol,56.3mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) were added in sequence to the reaction tube, and a cathode and an anode for reaction were made with platinum sheet electrodes, and finally triethylamine (6equiv,166uL), distilled water (20equiv,72uL) and dichloromethane (10mL) were added to the side branch ports, respectively, and electrolyzed at constant current under air conditions at room temperature for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction liquid, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, the solvent is evaporated in a rotary manner to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 58%, 29.6 mg.
1 H NMR(400MHz,Chloroform-d)δ3.34(q,J＝7.2Hz,2H),3.28(q,J＝7.2Hz,2H),2.25(t,J＝7.6Hz,2H),1.61(p,J＝7.2Hz,2H),1.34–1.21(m,16H),1.14(t,J＝7.2Hz,3H),1.08(t,J＝7.2Hz,3H),0.85(t,J＝6.8Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ172.4,42.1,40.1,33.3,32.0,29.7,29.7,29.7,29.6,29.6,29.4,25.6,22.8,14.5,14.2,13.2.
Example 8
Synthesis of
Figure BDA0003748252800000071
The oven-dried 25mL of the three-way tube was charged with the previously-dried stirring magneton, the amide twister (0.2mmol,45.8mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) were sequentially charged into the reaction tube, the cathode and anode for the reaction were made with platinum sheet electrodes, and finally triethylamine (6equiv,166uL), distilled water (20equiv,72uL) and dichloromethane (10mL) were added to the side branch ports, respectively, and the mixture was electrolyzed at constant current for 6 hours under air conditions at room temperature, and checked by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 48%, 19.5 mg.
1 H NMR(400MHz,Chloroform-d)δ7.70(d,J＝15.6Hz,1H),7.52(d,J＝6.8Hz,2H),7.35(t,J＝7.2Hz,3H),6.82(d,J＝15.2Hz,1H),3.48(p,J＝7.6Hz,4H),1.26(t,J＝7.2Hz,3H),1.19(t,J＝7.2Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ165.8,142.4,135.7,129.5,128.9,127.9,118.0,42.4,41.2,15.2,13.4.
Example 9
Synthesis of
Figure BDA0003748252800000072
To an oven-dried 25mL of a Y-piece was added a previously dried stirring magneton, then to a reaction tube were added amide twister (0.2mmol,40.6mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) in sequence, and to the reaction tube were used a platinum plate electrode as a cathode and an anode for the reaction, and finally to a side branch was added trihexylamine (6equiv,407uL), distilled water (20equiv,72uL) and dichloromethane (10mL) respectively, and to the tube was electrolyzed at constant current under air conditions at room temperature for 6 hours, and checked by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 62%, 35.9 mg.
1 H NMR(400MHz,Chloroform-d)δ7.41–7.29(m,5H),3.47(t,J＝8.0Hz,2H),3.16(t,J＝7.6Hz,2H),1.64(s,2H),1.47(s,2H),1.34(s,6H),1.20(s,2H),1.10(s,4H),0.89(s,3H),0.82(s,3H). 13 C NMR(100MHz,Chloroform-d)δ171.8,137.6,129.1,128.4,126.6,49.2,44.9,31.7,31.4,28.8,27.7,26.9,26.4,22.7,14.1.
Example 10
Synthesis of
Figure BDA0003748252800000081
Adding a pre-dried stirring magneton into a 25mL oven-dried Y-tube, sequentially adding amide twister (0.2mmol,40.6mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg) and ammonium sulfate (0.75equiv,19.8mg) into a reaction tube, using a platinum sheet electrode as a cathode and an anode for reaction, and finally adding triisopentylamine (6equiv,349uL), distilled water (20equiv,72uL) and dichloromethane (10mL) into side branch ports respectively, performing constant current electrolysis for 6 hours at room temperature under air conditions, and detecting by TLC until the amide twister is completely reacted. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 78%, 40.8 mg.
1 H NMR(400MHz,Chloroform-d)δ7.43–7.29(m,5H),3.49(s,2H),3.18(s,2H),1.73–1.32(m,6H),0.97(s,6H),0.73(s,6H). 13 C NMR(100MHz,Chloroform-d)δ171.6,137.4,129.1,128.3,126.5,47.5,43.4,37.8,36.5,26.4,25.8,22.6,22.4.
Example 11
Synthesis of
Figure BDA0003748252800000082
The method comprises the steps of adding a pre-dried stirring magneton into a 25mL oven-dried Y-tube, sequentially adding amide twister (0.2mmol,40.6mg), tribenzylamine (6equiv,344.9mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg) and ammonium sulfate (0.75equiv,19.8mg) into a reaction tube, using platinum sheet electrodes as a cathode and an anode of a reaction, and finally electrolyzing distilled water (20equiv,72uL) and dichloromethane (10mL) at a constant current at a lateral branch port under an air condition at room temperature for 6 hours until the amide twister reaction is complete through TLC detection. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 50%, 30.1 mg.
1 H NMR(400MHz,Chloroform-d)δ7.53–7.48(m,2H),7.39(d,J＝2.0Hz,2H),7.39–7.33(m,6H),7.30(t,J＝7.2Hz,3H),7.15(s,2H),4.71(s,2H),4.41(s,2H). 13 C NMR(100MHz,Chloroform-d)δ172.4,136.4,129.8,128.9,128.7,128.6,127.7,127.2,126.9,51.7,47.0.
Example 12
Synthesis of
Figure BDA0003748252800000091
Adding a predried stirring magneton into a 25mL oven-dried Y-pipe, sequentially adding an amide twister (0.2mmol,40.6mg), n-tetrabutylammonium bromide (0.75equiv,48.4mg) and ammonium sulfate (0.75equiv,19.8mg) into a reaction tube, using a platinum sheet electrode as a cathode and an anode for reaction, and finally adding tripentylamine (6equiv,349uL), distilled water (20equiv,72uL) and dichloromethane (10mL) into a side branch port respectively, carrying out constant current electrolysis for 6 hours at room temperature under an air condition, and detecting by TLC until the amide twister is completely reacted. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction liquid, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, the solvent is evaporated in a rotary manner to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 77%, 40.3 mg.
1 H NMR(400MHz,Chloroform-d)δ7.40–7.28(m,5H),3.44(d,J＝8.0Hz,2H),3.26–3.03(m,2H),1.63(s,2H),1.47(s,2H),1.34(s,4H),1.14(s,2H),1.06(s,2H),0.90(s,3H),0.79(s,3H). 13 C NMR(100MHz,Chloroform-d)δ171.7,137.5,129.0,128.4,126.5,49.1,44.8,29.3,28.7,28.4,27.3,22.5,22.2,14.0,14.0.
Example 13
Synthesis of
Figure BDA0003748252800000092
The oven-dried 25mL of the Y-tube was charged with the previously-dried stirring magneton, the amide twister (0.2mmol,40.6mg), N-tetrabutylammonium bromide (0.75equiv,48.4mg), ammonium sulfate (0.75equiv,19.8mg) were sequentially charged into the reaction tube, the cathode and anode for the reaction were made with platinum sheet electrodes, and finally N-methylpiperidine (6equiv,146uL), distilled water (20equiv,72uL) and dichloromethane (10mL) were added to the side branch ports, respectively, and the mixture was electrolyzed at constant current for 6 hours at room temperature under air conditions, and checked by TLC until the amide twister reaction was complete. After the reaction is finished, 5mL of saturated sodium chloride solution is added into the reaction solution, ethyl acetate is used for extraction (3X 10mL), organic phases are combined and dried by anhydrous sodium sulfate, filtration is carried out, rotary evaporation is carried out on a solvent to obtain a crude product, and finally column chromatography separation and purification are carried out to obtain a pure amide product. White liquid, yield 73%, 27.6 mg.
1 H NMR(400 MHz,Chloroform-d)δ7.37(s,5H),3.69(s,2H),3.33(s,2H),1.66(s,4H),1.51(s,2H). 13 C NMR(100 MHz,Chloroform-d)δ170.4,136.7,129.4,128.5,126.9,48.9,43.3,26.6,25.8,24.7。

Claims (4)

1. A novel method for electrocatalysis metal-free transamidation reaction is characterized in that: the new method takes a platinum electrode as a cathode and an anode of a reaction, takes an amide twister and tertiary amine as raw materials, takes n-tetrabutylammonium bromide as an electrolyte, takes ammonium sulfate as an additive and dichloromethane as a solvent, and synthesizes a tertiary amide product through constant-current electrochemical oxidation;
the method comprises the following specific steps:
step A: adding pre-dried stirring magnetons into the dried Y-pipe, and using platinum sheet electrodes as a cathode and an anode of a reaction; sequentially adding amide twister, n-tetrabutylammonium bromide and ammonium sulfate into a Y-tube, then respectively adding tertiary amine, distilled water and dichloromethane, electrolyzing for 6 hours under air condition and room temperature by constant current, wherein the current is a constant value of 6mA, and detecting by TLC until the amide twister is completely reacted;
and B, step B: after the reaction is finished, adding a saturated sodium chloride solution into the reaction solution, extracting with ethyl acetate for three times, drying the combined organic phase with anhydrous sodium sulfate, and separating and purifying by filtering, spin-drying a solvent and column chromatography to obtain an amide product.
2. The novel process of claim 1 for electrocatalytic metal-free transamidation reaction, wherein: the mol ratio of the amide twister, the n-tetrabutylammonium bromide, the ammonium sulfate and the tertiary amine is 4: 3: 24.
3. The novel process of claim 1 for electrocatalytic metal-free transamidation reaction, wherein: the ratio of the amide wrenching agent to the dichloromethane is 1: 50 according to mmol/mL.
4. The method of claim 1, wherein the reaction is carried out by electrocatalytic metal-free transamidationThe method comprises the following steps: the tertiary amine isN-methylpiperidine, trihexylamine, tripentylamine, triisopentylamine or tribenzylamine.
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