CN114990590B - A new method for electrocatalytic metal-free transamidation reaction - Google Patents
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- 238000000034 method Methods 0.000 title claims abstract description 15
- 238000007056 transamidation reaction Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 79
- 150000001408 amides Chemical class 0.000 claims abstract description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 56
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 36
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims abstract description 21
- 235000011130 ammonium sulphate Nutrition 0.000 claims abstract description 21
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 18
- 150000003512 tertiary amines Chemical class 0.000 claims abstract description 16
- 150000003511 tertiary amides Chemical class 0.000 claims abstract description 13
- 238000006056 electrooxidation reaction Methods 0.000 claims abstract description 4
- 239000000654 additive Substances 0.000 claims abstract description 3
- 230000000996 additive effect Effects 0.000 claims abstract description 3
- 239000003792 electrolyte Substances 0.000 claims abstract description 3
- 239000002994 raw material Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 45
- 241001589086 Bellapiscis medius Species 0.000 claims description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 33
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 15
- 238000004440 column chromatography Methods 0.000 claims description 15
- 239000012153 distilled water Substances 0.000 claims description 15
- 239000012074 organic phase Substances 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical group CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 8
- -1 4-phenylphenyl Chemical group 0.000 claims description 7
- QKVUSSUOYHTOFQ-UHFFFAOYSA-N 3-methyl-n,n-bis(3-methylbutyl)butan-1-amine Chemical compound CC(C)CCN(CCC(C)C)CCC(C)C QKVUSSUOYHTOFQ-UHFFFAOYSA-N 0.000 claims description 4
- MXHTZQSKTCCMFG-UHFFFAOYSA-N n,n-dibenzyl-1-phenylmethanamine Chemical compound C=1C=CC=CC=1CN(CC=1C=CC=CC=1)CC1=CC=CC=C1 MXHTZQSKTCCMFG-UHFFFAOYSA-N 0.000 claims description 4
- DIAIBWNEUYXDNL-UHFFFAOYSA-N n,n-dihexylhexan-1-amine Chemical compound CCCCCCN(CCCCCC)CCCCCC DIAIBWNEUYXDNL-UHFFFAOYSA-N 0.000 claims description 4
- OOHAUGDGCWURIT-UHFFFAOYSA-N n,n-dipentylpentan-1-amine Chemical compound CCCCCN(CCCCC)CCCCC OOHAUGDGCWURIT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 235000017803 cinnamon Nutrition 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 claims 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 241000723347 Cinnamomum Species 0.000 claims 1
- 238000000746 purification Methods 0.000 abstract description 14
- 238000000926 separation method Methods 0.000 abstract description 14
- 238000006555 catalytic reaction Methods 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 229910052723 transition metal Inorganic materials 0.000 abstract description 3
- 150000003624 transition metals Chemical class 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 238000003786 synthesis reaction Methods 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 18
- 239000000047 product Substances 0.000 description 16
- 238000005868 electrolysis reaction Methods 0.000 description 14
- 239000012043 crude product Substances 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 238000005910 aminocarbonylation reaction Methods 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000003948 formamides Chemical class 0.000 description 1
- WBGPNPZUWVTYAA-UHFFFAOYSA-N methane;dihydrochloride Chemical compound C.Cl.Cl WBGPNPZUWVTYAA-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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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
- C25B3/01—Products
- C25B3/09—Nitrogen containing compounds
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- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
- C25B3/20—Processes
- C25B3/23—Oxidation
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Abstract
Description
技术领域technical field
本发明一种电催化无金属转酰胺化反应的新方法涉及通过电催化氧化叔胺与酰胺扭曲子无金属转酰胺化反应，具体属于有机化学技术领域。The invention discloses a new method for electrocatalyzing metal-free transamidation reaction, which relates to metal-free transamidation reaction of oxidized tertiary amine and amide twister through electrocatalysis, and specifically belongs to the technical field of organic chemistry.
技术背景technical background
叔酰胺及其衍生物是天然产物、医药、农药、粘合剂和生物活性化合物的重要功能基序。由于叔酰胺的稳定性和重要性，开发一种简单的绿色可持续的氧化酰胺化策略用以合成叔酰胺类化合物成为当下研究的热门课题。通常酰胺是由胺与羧酸衍生物缩合反应合成的，但这看似简单的反应过程在温和条件下却难以反应，通常要加强热至高温或者借助于偶联试剂的帮助才能形成酰胺。传统的酰胺化学合成方法一般是采用偶联试剂将羧酸活化，通过活化的羧酸和胺发生缩合反应而完成的，或者是把羧酸转化成反应活性较高的酰氯或者酸酐后再与胺缩合反应。Tertiary amides and their derivatives are important functional motifs in natural products, medicines, pesticides, adhesives and bioactive compounds. Due to the stability and importance of tertiary amides, the development of a simple green and sustainable oxidative amidation strategy for the synthesis of tertiary amides has become a hot topic of current research. Amides are usually synthesized by the condensation reaction of amines and carboxylic acid derivatives, but this seemingly simple reaction process is difficult to react under mild conditions, and it is usually necessary to heat up to high temperatures or with the help of coupling reagents to form amides. The traditional amide chemical synthesis method is generally to activate the carboxylic acid with a coupling reagent, and then complete the condensation reaction between the activated carboxylic acid and the amine, or convert the carboxylic acid into a highly reactive acid chloride or acid anhydride and then react with the amine condensation reaction.
通常，叔酰胺的合成可以通过钯催化甲酸苄酯或芳基酯或酰胺与叔胺的反应制得(Xiao-Feng Wu等，Organic Chemistry Frontiers，2020,7(21),3406-3410；Yong-ShengBao等，Journal of Organic Chemistry，2014,79(2),803-808)。也可通过芳基硼酸与非活化叔胺通过C-N键活化Pd催化氧化的氨基羰基化反应制得(Bhanage,B.M.等，Journal ofOrganic Chemistry，2021,86(20),14028-14035)。虽然依靠传统方法可以有效的合成叔酰胺，但是叔酰胺的合成大都需要过渡金属催化，并且需要较高的温度和较长的反应时间。所以寻求一种条件温和的合成叔酰胺的方法成了目前基础有机合成中的一大挑战。Generally, the synthesis of tertiary amides can be prepared by palladium-catalyzed reaction of benzyl or aryl formate or amides with tertiary amines (Xiao-Feng Wu et al., Organic Chemistry Frontiers, 2020, 7(21), 3406-3410; Yong- Sheng Bao et al., Journal of Organic Chemistry, 2014, 79(2), 803-808). It can also be prepared by amino carbonylation reaction of aryl boronic acid with non-activated tertiary amine through C-N bond to activate Pd-catalyzed oxidation (Bhanage, B.M. et al., Journal of Organic Chemistry, 2021, 86(20), 14028-14035). Although tertiary amides can be effectively synthesized by traditional methods, most of the synthesis of tertiary amides requires transition metal catalysis, and requires higher temperature and longer reaction time. Therefore, finding a method for the synthesis of tertiary amides under mild conditions has become a major challenge in basic organic synthesis.
发明内容Contents of the invention
本发明的目的在于提供一种绿色环保的合成叔酰胺键的方法，以克服现有合成方法存在不足。The purpose of the present invention is to provide a green and environment-friendly method for synthesizing tertiary amide bonds, so as to overcome the shortcomings of existing synthetic methods.
本发明一种电催化无金属转酰胺化反应的新方法以铂电极作反应的阴极和阳极，酰胺扭曲子和叔胺为原料，正四丁基溴化铵为电解质，硫酸铵为添加剂，二氯甲烷为溶剂，通过恒电流电化学氧化，合成叔酰胺产物；A new method of electrocatalytic metal-free transamidation reaction of the present invention uses a platinum electrode as the cathode and anode of the reaction, amide twisters and tertiary amines as raw materials, n-tetrabutylammonium bromide as electrolyte, ammonium sulfate as additive, dichloride Methane is used as a solvent, and tertiary amide products are synthesized through constant current electrochemical oxidation;
具体步骤为：The specific steps are:
步骤A：向干燥的三叉管中加入预先干燥的搅拌磁子，用铂片电极作为反应的阴极和阳极；将酰胺扭曲子、正四丁基溴化铵(0.75equiv)和硫酸铵(0.75equiv)依次加入三叉管中，其后再分别加入叔胺(6equiv)、蒸馏水(20equiv)和二氯甲烷，在空气条件和室温下，通过恒电流电解6小时，电流为恒定值6mA，通过TLC检测直到酰胺扭曲子反应完全；Step A: Add the pre-dried stirring magnet to the dry trifurcated tube, use the platinum plate electrode as the cathode and anode of the reaction; add the amide twister, n-tetrabutylammonium bromide (0.75equiv) and ammonium sulfate (0.75equiv) Add in the trifurcated tube successively, then add tertiary amine (6equiv), distilled water (20equiv) and methylene chloride respectively again afterwards, under air condition and room temperature, by constant current electrolysis 6 hours, electric current is constant value 6mA, detects by TLC until The amide twister reacts completely;
步骤B：反应结束后，向反应液中加入饱和氯化钠溶液，再用乙酸乙酯萃取三次，合并的有机相用无水硫酸钠干燥，再经过滤、旋干溶剂和柱层析分离提纯，得到酰胺产物。Step B: After the reaction is completed, add saturated sodium chloride solution to the reaction solution, then extract three times with ethyl acetate, and dry the combined organic phase with anhydrous sodium sulfate, then filter, spin to dry the solvent and separate and purify by column chromatography , to give the amide product.
所述的酰胺扭曲子、正四丁基溴化铵、硫酸铵和叔胺的摩尔比为4∶3∶3∶24。The molar ratio of the amide twister, n-tetrabutylammonium bromide, ammonium sulfate and tertiary amine is 4:3:3:24.
所述的酰胺扭曲子和二氯甲烷按mmol/mL计，比例为1∶50。The amide twister and dichloromethane are calculated in mmol/mL, and the ratio is 1:50.
所述的叔胺为N-甲基哌啶、三己胺、三戊胺、三异戊胺或三苄胺。The tertiary amine is N-methylpiperidine, trihexylamine, tripentylamine, triisopentylamine or tribenzylamine.
本发明电催化无金属转酰胺化反应可能的机理如下：The possible mechanism of electrocatalytic metal-free transamidation reaction of the present invention is as follows:
三乙胺a在阳极被氧化为自由基正离子b，然后再与另一分子三乙胺进行质子交换得到N的α碳自由基c,再失去一个电子成为亚胺正离子中间体d，最后再水解得到二烷基胺关键中间体e。再与酰胺扭曲子进行简单的亲核加成反应，得到四面体中间体f,最后中间体f分解为目标产物g。Triethylamine a is oxidized to a free radical cation b at the anode, and then undergoes proton exchange with another molecule of triethylamine to obtain the α-carbon free radical c of N, and then loses an electron to become an iminium cation intermediate d, and finally Then hydrolyze to obtain the key intermediate e of dialkylamine. A simple nucleophilic addition reaction with the amide twister yields the tetrahedral intermediate f, and finally the intermediate f decomposes into the target product g.
所述通过酰胺扭曲子与叔胺电化学氧化合成叔酰胺的反应式为：The reaction formula for the synthesis of tertiary amides by electrochemical oxidation of amide twisters and tertiary amines is:
其中：R1为苯基、4-甲氧基苯基、4-甲基苯基、4-苯基苯基、2-氯噻吩基、2,6-二甲基苄基、十一烷基、肉桂基；Among them: R 1 is phenyl, 4-methoxyphenyl, 4-methylphenyl, 4-phenylphenyl, 2-chlorothienyl, 2,6-dimethylbenzyl, undecyl , cinnamon base;
R3不等于R2时，叔胺为N-甲基哌啶；R3等于R2时，叔胺为三己胺、三戊胺、三异戊胺和三苄胺。When R 3 is not equal to R 2 , the tertiary amine is N-methylpiperidine; when R 3 is equal to R 2 , the tertiary amine is trihexylamine, tripentylamine, triisopentylamine and tribenzylamine.
本发明的有益效果是：本发明相比于传统合成叔酰胺的方法，不需要过渡金属催化，直接利用电化学条件促使反应进行，条件温和、操作简单、收率高便于分离提纯，且绿色环保，底物适用范围广。The beneficial effects of the present invention are: compared with the traditional method for synthesizing tertiary amides, the present invention does not require transition metal catalysis, and directly utilizes electrochemical conditions to promote the reaction. The conditions are mild, the operation is simple, the yield is high, easy to separate and purify, and it is environmentally friendly. , a wide range of substrates.
具体实施方式Detailed ways
下面结合实施例1-13来详细说明本发明所具有的有益效果，旨在帮助阅读者更好地理解本发明的实质，但不能对本发明的实施和保护范围构成任何限定。The beneficial effects of the present invention will be described in detail below in conjunction with Examples 1-13, aiming to help readers better understand the essence of the present invention, but not to limit the implementation and protection scope of the present invention.
实施例1Example 1
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,40.6mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三乙胺(6equiv,166uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率78％,27.6mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 40.6mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triethylamine (6equiv, 166uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 78%, 27.6mg.
1H 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).13C NMR(100MHz,Chloroform-d)δ171.4,137.4,129.2,128.5,126.4,43.4,39.3,14.3,13.0. 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.
实施例2Example 2
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,46.6mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三乙胺(6equiv,166uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率78％,32.3mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 46.6mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triethylamine (6equiv, 166uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 78%, 32.3mg.
1H 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).13C NMR(100MHz,Chloroform-d)δ171.3,160.4,129.6,128.3,113.8,55.4,43.2,39.4,13.9,13.3. 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.
实施例3Example 3
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,43.4mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三乙胺(6equiv,166uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率80％,30.6mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 43.4mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triethylamine (6equiv, 166uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 80%, 30.6mg.
1H 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).13C NMR(100MHz,Chloroform-d)δ171.6,139.2,134.5,129.1,126.5,43.4,39.4,21.5,14.3,13.1. 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 .
实施例4Example 4
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,55.9mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三乙胺(6equiv,166uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率78％,39.5mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 55.9mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triethylamine (6equiv, 166uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 78%, 39.5mg.
1H 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).13C 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. 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.
实施例5Example 5
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,48.7mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三乙胺(6equiv,166uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率65％,28.3mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 48.7mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triethylamine (6equiv, 166uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 65%, 28.3mg.
1H 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).13C NMR(100MHz,Chloroform-d)δ162.5,137.3,133.8,127.7,126.1,42.3,13.7. 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.
实施例6Example 6
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,49.0mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三乙胺(6equiv,166uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率50％,21.9mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 49.0mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triethylamine (6equiv, 166uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 50%, 21.9mg.
1H 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).13C 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. 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=7.2 Hz, 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.
实施例7Example 7
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,56.3mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三乙胺(6equiv,166uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率58％,29.6mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 56.3mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triethylamine (6equiv, 166uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 58%, 29.6mg.
1H 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).13C 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. 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=6.8 Hz,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.
实施例8Example 8
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,45.8mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三乙胺(6equiv,166uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率48％,19.5mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 45.8mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triethylamine (6equiv, 166uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 48%, 19.5mg.
1H 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).13C 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. 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.
实施例9Example 9
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,40.6mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三己胺(6equiv,407uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率62％,35.9mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 40.6mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using a platinum plate electrode as the cathode and anode of the reaction, and finally adding trihexylamine (6equiv, 407uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 62%, 35.9mg.
1H 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).13C 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. 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.
实施例10Example 10
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,40.6mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三异戊胺(6equiv,349uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率78％,40.8mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 40.6mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, using platinum electrodes as the cathode and anode of the reaction, and finally adding triisoamylamine (6equiv, 349uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) into the side branch respectively Constant current electrolysis was performed at room temperature under air conditions for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 78%, 40.8mg.
1H 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).13C 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. 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.
实施例11Example 11
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,40.6mg)，三苄胺(6equiv,344.9mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率50％,30.1mg。Add the pre-dried stirring magnet to the oven-dried 25mL trifurcated tube, and add amide twister (0.2mmol, 40.6mg), tribenzylamine (6equiv, 344.9mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) was added to the reaction tube in turn, and the cathode and anode of the reaction were made of platinum electrodes, and finally distilled water (20equiv, 72uL) and dichloromethane (10mL) were placed in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 50%, 30.1mg.
1H 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).13C 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. 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.
实施例12Example 12
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,40.6mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入三戊胺(6equiv,349uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率77％,40.3mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 40.6mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) into the reaction tube in turn, use platinum electrode as the cathode and anode of the reaction, and finally add tripentylamine (6equiv, 349uL), distilled water (20equiv, 72uL) and dichloromethane (10mL) in the side branch respectively. Constant current electrolysis was carried out at room temperature under air condition for 6 hours, and detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 77%, 40.3mg.
1H 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).13C 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. 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.
实施例13Example 13
合成synthesis
向经过烘箱干燥的25mL三叉管中加入预先干燥的搅拌磁子，再将酰胺扭曲子(0.2mmol,40.6mg)，正四丁基溴化铵(0.75equiv,48.4mg)，硫酸铵(0.75equiv,19.8mg)依次加入反应管中，用铂片电极做反应的阴极和阳极，最后在侧面支口分别加入N-甲基哌啶(6equiv,146uL)，蒸馏水(20equiv,72uL)和二氯甲烷(10mL)在空气条件室温下恒电流电解6小时，通过TLC检测直到酰胺扭曲子反应完全。反应结束后，向反应液中加入5mL的饱和氯化钠溶液，再用乙酸乙酯萃取(3×10mL)，合并有机相并用无水硫酸钠干燥，过滤，旋蒸旋干溶剂得粗产物，最后进行柱层析分离提纯得到纯净的酰胺产物。白色液体，收率73％,27.6mg。Add the pre-dried stirring magnet to the oven-dried 25mL trident tube, then add the amide twister (0.2mmol, 40.6mg), n-tetrabutylammonium bromide (0.75equiv, 48.4mg), ammonium sulfate (0.75equiv, 19.8mg) was added to the reaction tube in turn, and the cathode and anode of the reaction were made of platinum electrodes. Finally, N-methylpiperidine (6equiv, 146uL), distilled water (20equiv, 72uL) and dichloromethane ( 10 mL) was subjected to constant current electrolysis at room temperature under air conditions for 6 hours, and was detected by TLC until the amide twister reaction was complete. After the reaction, add 5 mL of saturated sodium chloride solution to the reaction solution, then extract with ethyl acetate (3 × 10 mL), combine the organic phases and dry with anhydrous sodium sulfate, filter, spin to dry the solvent to obtain a crude product, Finally, separation and purification by column chromatography was carried out to obtain a pure amide product. White liquid, yield 73%, 27.6mg.
1H 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).13C 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。 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.
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