CN118223046A - Electrochemical preparation method of oxazoline compound containing sulfonamide group - Google Patents
Electrochemical preparation method of oxazoline compound containing sulfonamide group Download PDFInfo
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- -1 oxazoline compound Chemical class 0.000 title claims abstract description 60
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 125000000565 sulfonamide group Chemical group 0.000 title description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 129
- 238000000605 extraction Methods 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 22
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 239000003792 electrolyte Substances 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract 2
- 239000000047 product Substances 0.000 claims description 105
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 81
- 239000012043 crude product Substances 0.000 claims description 54
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 46
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 36
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 29
- 238000004440 column chromatography Methods 0.000 claims description 28
- 239000007810 chemical reaction solvent Substances 0.000 claims description 27
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 26
- 239000007788 liquid Substances 0.000 claims description 26
- MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 claims description 24
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 23
- 229910052697 platinum Inorganic materials 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 229910021397 glassy carbon Inorganic materials 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 6
- 239000001632 sodium acetate Substances 0.000 claims description 6
- 235000017281 sodium acetate Nutrition 0.000 claims description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 6
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 3
- 235000011009 potassium phosphates Nutrition 0.000 claims description 3
- KBLZDCFTQSIIOH-UHFFFAOYSA-M tetrabutylazanium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC KBLZDCFTQSIIOH-UHFFFAOYSA-M 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 2
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- GWBBLCMZKBNNEC-UHFFFAOYSA-N N-(2-phenylprop-2-enyl)benzamide Chemical class C1(=CC=CC=C1)C(CNC(C1=CC=CC=C1)=O)=C GWBBLCMZKBNNEC-UHFFFAOYSA-N 0.000 abstract description 24
- 239000007800 oxidant agent Substances 0.000 abstract description 7
- 230000001590 oxidative effect Effects 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 5
- 239000003054 catalyst Substances 0.000 abstract description 4
- 125000001424 substituent group Chemical group 0.000 abstract description 4
- 238000003760 magnetic stirring Methods 0.000 abstract description 2
- 229910052723 transition metal Inorganic materials 0.000 abstract description 2
- 150000003624 transition metals Chemical class 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 53
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
- 238000001514 detection method Methods 0.000 description 25
- 238000005868 electrolysis reaction Methods 0.000 description 25
- GWLOGZRVYXAHRE-UHFFFAOYSA-N n,4-dimethylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(C)C=C1 GWLOGZRVYXAHRE-UHFFFAOYSA-N 0.000 description 23
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 238000001228 spectrum Methods 0.000 description 15
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 230000002194 synthesizing effect Effects 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 238000005576 amination reaction Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 150000002918 oxazolines Chemical class 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- UIVZZDAOKBAWCS-UHFFFAOYSA-N 4-methoxy-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(OC)C=C1 UIVZZDAOKBAWCS-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- XYUDFTCYGYHTHO-UHFFFAOYSA-N O=S(=N[N+]1=CC=CC=C1)=O Chemical class O=S(=N[N+]1=CC=CC=C1)=O XYUDFTCYGYHTHO-UHFFFAOYSA-N 0.000 description 1
- DORMTBIPKNPJPY-UHFFFAOYSA-N acetic acid;iodobenzene Chemical compound CC(O)=O.IC1=CC=CC=C1 DORMTBIPKNPJPY-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000006399 aminohydroxylation reaction Methods 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 125000004421 aryl sulphonamide group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229940072185 drug for treatment of tuberculosis Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000000806 fluorine-19 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 1
- NRKCZBWVAQJOOG-UHFFFAOYSA-N n-methyl-4-(trifluoromethyl)benzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 NRKCZBWVAQJOOG-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000007146 photocatalysis Methods 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000012363 selectfluor Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
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- Electrolytic Production Of Non-Metals, Compounds, Apparatuses Therefor (AREA)
Abstract
The invention discloses an electrochemical preparation method of an N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound. The method comprises the following steps: sequentially adding N- (2-phenylallyl) benzamide compounds, N-methyl aryl sulfonamide compounds, electrolyte, electrolytic solvent, alkali and magnetic stirring rod into a diaphragm-free electrolytic cell, inserting an anode and a cathode, stirring, electrifying, reacting under constant current, performing organic extraction on the reaction solution by using an organic solvent after the reaction is completed, and separating and purifying to obtain a target product. The method does not need to additionally add an oxidant and a transition metal catalyst. The reaction raw materials are cheap and easy to obtain, the yield is higher, and the selectivity is good. The substrate of the reaction has wider application range and high substituent compatibility. The reaction system is simple and effective and is environment-friendly. The reaction of the method is operated at normal temperature and normal pressure, and is simple and safe.
Description
Technical Field
The invention belongs to the technical field of electrochemical organic synthesis, and particularly relates to an electrochemical preparation method of an N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound.
Background
Nitrogen-containing heterocycles are widely used in natural products and biological medicine, wherein oxazolines are important nitrogen-containing heterocyclic compounds containing oxygen atoms. They are the core backbones that constitute some natural products, drugs, functional materials and bioactive molecules, as well as important intermediates and chemical ligands in organic synthesis reactions. In addition, sulfonamide compounds are widely present in drug molecules and bioactive compounds, play an important role in drug design and synthesis, and are useful as anti-inflammatory agents, antibiotics, antihypertensive agents, etc., wherein the sulfonamide group is an important functional group in sulfonamide compounds. Based on important application properties of the oxazoline compound and the sulfonamide group, the synthesis of the oxazoline compound containing the sulfonamide group has important significance. In recent years, a method for synthesizing an oxazoline derivative by introducing a second group into an N-allylamide derivative and then carrying out intramolecular cyclization reaction has been reported. The reaction conditions of the method are relatively mild, the substrate structure is simple, and the method is an effective strategy for synthesizing the oxazoline compound.
N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound has oxazoline skeleton and sulfonamide group, provides an important compound for pharmaceutical chemistry, but the synthetic method is few, and greatly limits the application of the compound. Up to now, there are four methods for synthesizing oxazolines with sulfonamide groups by using N-allylamide compounds as raw materials. In 2017, teams Ji Lianwen and Zhang Bo synthesized N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N- (phenylsulfonyl) benzenesulfonamide .[Xie,J.;Wang,Y.-W.;Qi,L.-W.;Zhang,B.Access to Aminated Saturated Oxygen Heterocycles via Copper-Catalyzed Aminooxygenation of Alkenes[J].Org.Lett.,2017,19(5):1148-1151.]2018 in 41% yield using NFSI and N- (2-phenylallyl) benzamide as starting materials under copper catalysis at 70℃and Choi and Hong teams reported a high valent iodine mediated oxyalkylation of N-allylamide using N- (2-phenylallyl) benzamide compound and electron deficient amine Ts 2 NH as starting materials, Iodobenzene acetate is taken as an oxidant, dichloroethane is taken as a solvent, a series of 4-methyl-N- ((2-aryl-4, 5-dihydro-oxazol-5-yl) methyl) -N-toluenesulfonyl benzene sulfonamide compounds are synthesized under the condition of 50 ℃ for .[Jeon,H.;Kim,D.;Lee,J.H.;Song,J.;Lee,W.S.;Kang,D.W.;Kang,S.;Lee,S.B.;Choi,S.;Hong,K.B.Hypervalent Iodine-Mediated Alkene Functionalization:Oxazoline and Thiazoline Synthesis via Inter-/Intramolecular Aminohydroxylation and Thioamination[J].Adv.Synth.Catal.,2017,360(4):779-783.]2021 years, the Hashimoto subject group provides a chiral organic iodine catalyzed enantioselective oxyammox reaction of N-allylamide compounds and amine compounds, the reaction utilizes N- (fluoro sulfonyl) carbamate as an amination reagent, a Selectfluor reagent is taken as an oxidant, A series of benzyl (R) - (fluoro sulfonyl) ((2-aryl (alkyl) -4, 5-dihydro-oxazol-5-yl) methyl) carbamate compounds can be obtained by reacting for 18-24 hours at 10 ℃ for .[Wata,C.;Hashimoto,T.Organoiodine-Catalyzed Enantioselective Intramolecular Oxy-aminations of Alkenes with N-(Fluorosulfonyl)carbamate[J].Synthesis,2021,53(15):2594-2601.]2023 years, N-sulfonylaminopyridinium salt is taken as an amination reagent in Jin Tao and Zhu Chengjian groups, 4CzIPN is taken as a photocatalyst, a series of N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) arylsulfonamide compounds .[Pan,C.;Yang,Z.;Wu,X.;Yu,J.-T.;Zhu,C.Substituent-Controlled Regioselective Photoinduced Cyclization of N-Allylbenzamides with N-Sulfonylaminopyridinium Salts[J].Org.Lett.,2023,25(3):494-499.] can be synthesized under the photocatalysis condition, although the four methods can all effectively obtain oxazoline compounds containing sulfonamide groups, There are certain limitations. From the reaction conditions point of view, they require the addition of additional oxidizing agents or transition metal catalysts and are mostly reactive at non-ambient temperatures. In view of the application range of the substrate, the pre-activated amine compound or the amine compound with two strong electron withdrawing groups on nitrogen atoms is required to be used as an amination reagent, and in addition, the substituent effect of the benzene ring of the olefin part in the N-allylamide compound is not explored in the reactions. Accordingly, the present invention is directed to further developing a green, efficient and atom-economical method for synthesizing N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide-based compounds.
Disclosure of Invention
In order to overcome the scarcity and limitation of the current methods for synthesizing such compounds, the invention aims to provide an electrochemical preparation method of N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compounds.
The N-methyl aryl sulfonamide compound used in the method does not need to be pre-activated, and is simple and easy to obtain; the electrodes are all common inert electrodes, and electrode modification is not needed; no additional metal catalyst and toxic oxidant are needed; the reaction raw materials are cheap and easy to obtain, the yield is higher, and the selectivity is good; the application range of the substrate is wider, and the compatibility of the substituent is high; the reaction system is simple and effective and is environment-friendly. The reaction of the method is operated at normal temperature and normal pressure, and is simple and safe.
The aim of the invention is achieved by the following technical scheme.
N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound with a structural general formula shown in formula (I),
Wherein R, R 1 and R 2 represent electron withdrawing groups or electron donating groups, the electron withdrawing groups are selected from one of halogen and trifluoromethyl, and the electron donating groups are selected from one of methoxy, methyl and tert-butyl.
The electrochemical preparation method of the N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound comprises the following steps:
N- (2-phenylallyl) benzamide compound (1) and N-methyl aryl sulfonamide compound (2) are used as raw materials, the N- (2-phenylallyl) benzamide compound, electrolyte, alkali, electrolytic solvent and magnetic stirring rod are sequentially added into a diaphragm-free electrolytic cell, then an anode and a cathode are inserted, the reaction solution is continuously stirred and electrified, the reaction is carried out under the constant current condition, and the reaction progress is detected by TLC. After the reaction is finished, part of the reaction solvent is removed through vacuum concentration, then organic solvent is used for carrying out organic extraction on the reaction solution, then the extraction solution is subjected to vacuum concentration to obtain a crude product, and then the crude product is separated and purified through column chromatography to obtain the N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound.
The synthetic route of the invention is as follows:
R, R 1 and R 2 in compounds 1, 2, 3 correspond to the optional groups of the above general formula (I).
Preferably, the dosage of the N-methyl aryl sulfonamide compound is 150% -250% of the molar weight of the N- (2-phenylallyl) benzamide compound.
Preferably, the electrolyte is one of tetrabutylammonium acetate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium perchlorate and sodium acetate.
Preferably, the molar concentration of the electrolyte in the electrolytic solvent is 0.04-0.08mol/L.
Preferably, the base is one of potassium carbonate, sodium acetate, potassium phosphate, 1, 8-diazabicyclo [5.4.0] undec-7-ene and triethylamine.
Preferably, the amount of the base is 200% -250% of the molar amount of the N- (2-phenylallyl) benzamide compound.
Preferably, the electrolytic solvent is one of a mixed solution of 1, 2-dichloroethane and hexafluoroisopropanol (v: v=1:1-3:1) and a mixed solution of dichloromethane and hexafluoroisopropanol (v: v=1:1-3:1).
Preferably, the anode is one of a carbon electrode and a reticulated vitreous carbon electrode (RVC).
Preferably, the cathode is one of a platinum electrode and a nickel electrode.
Preferably, the current of the reaction is 2-4mA.
Preferably, the temperature of the reaction is room temperature.
Preferably, the reaction time is 5h 15min-10.5h.
Preferably, the organic solvent is ethyl acetate.
Preferably, the separation and purification mode is column chromatography separation and purification.
The N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound prepared by the invention can be used for preparing antituberculosis drugs, antibiotics, synthetic intermediates and the like.
Compared with the prior art, the preparation method provided by the invention has the following advantages:
(1) The invention utilizes the electrochemical organic synthesis method, takes electrons as an oxidant, takes N- (2-phenylallyl) benzamide compounds and N-methyl aryl sulfonamide compounds which do not need pre-activation and are simple and easy to process as raw materials, and can synthesize N- ((2, 5-diphenyl-4, 5-dihydro oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compounds under simple and convenient conditions.
(2) The electrodes used in the method are all common inert electrodes, and electrode modification is not needed; the anode is an inert electrode, so that the problem of metal anode consumption is solved, and the yield is high.
(3) The invention does not need to additionally add expensive metal catalyst and oxidant, and the reaction system is simple and efficient and environment-friendly.
(4) The method has the advantages of wide substrate adaptation range, high substituent compatibility, good reaction selectivity, high yield and simple operation.
(5) The method avoids the severe conditions of high temperature and high pressure, and the reaction is operated at normal temperature and normal pressure, so that the method is simple and safe.
Drawings
FIG. 1 is a 1 H NMR spectrum of product 3a of the example of the invention.
FIG. 2 is a 13 C NMR spectrum of product 3a of the example of the invention.
FIG. 3 is a 1 H NMR spectrum of product 3b of the example of the invention.
FIG. 4 is a 13 C NMR spectrum of product 3b of the example of the invention.
FIG. 5 is a 1 H NMR spectrum of product 3c of the example of the invention.
FIG. 6 is a 13 C NMR spectrum of product 3C of the example of the invention.
FIG. 7 is a 1 H NMR spectrum of product 3d of the example of the invention.
FIG. 8 is a 13 C NMR spectrum of product 3d of the example of the invention.
FIG. 9 is a 1 H NMR spectrum of product 3e of the example of the invention.
FIG. 10 is a 13 C NMR chart of product 3e of the example of the invention.
FIG. 11 is a 1 H NMR spectrum of product 3f of the example of the invention.
FIG. 12 is a 13 C NMR spectrum of product 3f of the example of the invention.
FIG. 13 is a 1 H NMR spectrum of the product of example 3g according to the invention.
FIG. 14 is a 13 C NMR spectrum of the product of example 3g of the invention.
FIG. 15 is a 19 F NMR spectrum of the product of example 3g of the invention.
Detailed Description
The present invention will be described in further detail with reference to examples, but embodiments of the present invention are not limited thereto.
Example 1
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a mesh glassy carbon (RVC) as an anode, the cathode and anode were inserted, a lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 72%.
The reaction scheme of this example is shown in the following formula:
The nuclear magnetic resonance hydrogen spectrum of the product of the example is shown in figure 1, and the ：1H NMR(500MHz,CDCl3)δ8.02(d,J＝7.2Hz,2H),7.58(d,J＝8.2Hz,2H),7.52-7.48(m,1H),7.45-7.42(m,4H),7.40-7.37(m,2H),7.33-7.30(m,1H),7.26(d,J＝8.2Hz,2H),4.71(d,J＝15.1Hz,1H),4.21(d,J＝15.1Hz,1H),3.69(d,J＝14.6Hz,1H),3.44(d,J＝14.7Hz,1H),2.72(s,3H),2.39(s,3H); nuclear magnetic resonance carbon spectrum is shown in figure 2 ：13C NMR(101MHz,CDCl3):δ162.3,143.6,142.5,134.4,131.5,129.8,128.8,128.5,128.1,128.0,127.6,127.5,124.9,89.3,65.0,58.0,37.3,21.5.
From the above data, the synthesized product was identified to be N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide.
Example 2
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (55.6 mg,150mol%,0.3 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, the lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 61%.
The reaction scheme of this example is shown in the following formula:
Example 3
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (92.6 mg,250mol%,0.5 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, the lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 45%.
The reaction scheme of this example is shown in the following formula:
Example 4
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (120.6 mg,0.08 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, the magnetic stirrer was turned on, the power was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 50%.
The reaction scheme of this example is shown in the following formula:
Example 5
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium tetrafluoroborate (65.8 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as an anode, the cathode and the anode were inserted, a lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 56%.
The reaction scheme of this example is shown in the following formula:
Example 6
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium perchlorate (68.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as an anode, the cathode and the anode were inserted, a lid was closed, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 57%.
The reaction scheme of this example is shown in the following formula:
Example 7
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), sodium acetate (16.4 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a mesh glassy carbon (RVC) as an anode, the cathode and anode were inserted, the lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 58%.
The reaction scheme of this example is shown in the following formula:
Example 8
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium phosphate (84.9 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, the magnetic stirrer was turned on, the power was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 55%.
The reaction scheme of this example is shown in the following formula:
Example 9
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), sodium acetate (32.8 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a mesh glassy carbon (RVC) as an anode, the cathode and anode were inserted, a lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 62%.
The reaction scheme of this example is shown in the following formula:
Example 10
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), 1, 8-diazabicyclo [5.4.0] undec-7-ene (60.0. Mu.L, 200mol%,0.4 mmol), 1, 2-dichloroethane and hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask using a Reticulated Vitreous Carbon (RVC) as an anode, the cathode and anode were inserted, the lid was closed, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 63%.
The reaction scheme of this example is shown in the following formula:
Example 11
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), triethylamine (56.0. Mu.L, 200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, a lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 63%.
The reaction scheme of this example is shown in the following formula:
example 12
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (69.1 mg,250mol%,0.5 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, the lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 62%.
The reaction scheme of this example is shown in the following formula:
example 13
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), dichloromethane and hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a mesh glassy carbon (RVC) as an anode, the cathode and the anode were inserted, the lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, the electrolysis was performed for 7h at a constant temperature and a constant current, and the detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 50%.
The reaction scheme of this example is shown in the following formula:
Example 14
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (1:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a mesh glassy carbon (RVC) as an anode, the cathode and anode were inserted, a lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 56%.
The reaction scheme of this example is shown in the following formula:
Example 15
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (3:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, the magnetic stirrer was turned on, the power was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 50%.
The reaction scheme of this example is shown in the following formula:
Example 16
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer are sequentially added into a 5mL round bottom reaction flask by taking a carbon rod as an anode, the cathode and the anode are inserted, a cover is covered, a magnetic stirrer is turned on, the current is adjusted to 3mA, the electrolysis is performed for 7h under the conditions of low temperature and current, and the detection is performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 39%.
The reaction scheme of this example is shown in the following formula:
Example 17
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a mesh glassy carbon (RVC) as an anode, the cathode and anode were inserted, a lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 55%.
The reaction scheme of this example is shown in the following formula:
Example 18
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, the magnetic stirrer was turned on, the power was turned on, the current was adjusted to 2mA, and electrolysis was performed for 10.5h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 61%.
The reaction scheme of this example is shown in the following formula:
Example 19
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as the anode, the cathode and anode were inserted, the magnetic stirrer was turned on, the power was turned on, the current was adjusted to 4mA, and electrolysis was performed for 5h 15min at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3a, wherein the product 3a is colorless oily liquid. The yield of product 3a was 65%.
The reaction scheme of this example is shown in the following formula:
Example 20
A Reticulated Vitreous Carbon (RVC) was used as the anode and a platinum electrode was used as the cathode, and 4-chloro-N- (2-phenylallyl) benzamide 1b (54.3 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask, the cathode and anode were inserted, the lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3b, wherein the product 3b is colorless oily liquid. The yield of product 3b was 81%.
The reaction scheme of this example is shown in the following formula:
the nuclear magnetic resonance hydrogen spectrum of the product of the example is shown in FIG. 3, and the ：1H NMR(500MHz,CDCl3)δ7.87(d,J＝8.5Hz,2H),7.49(d,J＝8.0Hz,2H),7.34-7.28(m,6H),7.24-7.21(m,1H),7.18-7.16(m,2H),4.63(d,J＝15.1Hz,1H),4.11(d,J＝15.1Hz,1H),3.62(d,J＝14.7Hz,1H),3.30(d,J＝14.7Hz,1H),2.59(s,3H),2.29(s,3H); nuclear magnetic resonance carbon spectrum is shown in FIG. 4 ：13C NMR(101MHz,CDCl3):δ161.5,143.7,142.2,137.7,134.4,129.8,129.5,128.84,128.80,128.1,127.5,126.1,124.8,89.6,64.9,58.1,37.4,21.5.
From the above data, the synthesized product was identified to be N- ((2- (4-chlorophenyl) -5-phenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide.
Example 21
A Reticulated Vitreous Carbon (RVC) was used as the anode and a platinum electrode was used as the cathode, 4-methoxy-N- (2-phenylallyl) benzamide 1c (53.4 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask, the cathode and anode were inserted, the lid was turned on, the magnetic stirrer was turned on, the current was adjusted to 3mA, electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3c, wherein the product 3c is colorless oily liquid. The yield of product 3c was 56%.
The reaction scheme of this example is shown in the following formula:
The nuclear magnetic resonance hydrogen spectrum of the product of the example is shown in FIG. 5, and the ：1H NMR(500MHz,CDCl3)δ7.96(d,J＝8.8Hz,2H),7.58(d,J＝8.0Hz,2H),7.44-7.37(m,4H),7.33-7.30(m,1H),7.28-7.26(m,2H),6.94(d,J＝8.9Hz,2H),4.65(d,J＝14.8Hz,1H),4.17(d,J＝14.8Hz,1H),3.85(s,3H),3.67(d,J＝14.7Hz,1H),3.45(d,J＝14.7Hz,1H),2.71(s,3H),2.40(s,3H); nuclear magnetic resonance carbon spectrum is shown in FIG. 6 ：13C NMR(101MHz,CDCl3):δ162.3,143.6,142.5,134.5,129.9,129.7,128.7,127.9,127.5,124.9,113.9,89.1,64.9,57.9,55.4,37.2,21.5.
From the above data, the synthesized product was identified to be N- ((2- (4-methoxyphenyl) -5-phenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide.
Example 22
N- (2- (4- (tert-butyl) phenyl) allyl) benzamide 1d (58.6 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask using a Reticulated Vitreous Carbon (RVC) as an anode, the cathode and anode were inserted, the lid was closed, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3d, wherein the product 3d is colorless oily liquid. The yield of product 3d was 45%.
The reaction scheme of this example is shown in the following formula:
The nuclear magnetic resonance hydrogen spectrum of the product of this example is shown in FIG. 7, and the ：1H NMR(500MHz,CDCl3)δ8.01(d,J＝7.2Hz,2H),7.59(d,J＝8.2Hz,2H),7.51-7.48(m,1H),7.45-7.40(m,4H),7.36(d,J＝8.5Hz,2H),7.27(d,J＝7.8Hz,2H),4.71(d,J＝15.1Hz,1H),4.20(d,J＝15.0Hz,1H),3.71(d,J＝14.7Hz,1H),3.39(d,J＝14.7Hz,1H),2.73(s,3H),2.40(s,3H),1.31(s,9H); nuclear magnetic resonance carbon spectrum is shown in FIG. 8 ：13C NMR(101MHz,CDCl3):δ162.2,151.0,143.6,139.5,134.5,131.5,129.7,128.5,128.1,127.7,127.5,125.6,124.6,89.3,64.8,57.8,37.3,34.5,31.3,21.5.
From the above data, the synthesized product was identified as N- ((5- (4- (tert-butyl) phenyl) -2-phenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide.
Example 23
N- (2- (3-bromophenyl) allyl) benzamide 1e (63.2 mg,0.2 mmol), N-methyl-p-toluenesulfonamide 2a (74.1 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as an anode, the cathode and anode were inserted, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at a constant temperature and under a constant current condition, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3e, wherein the product 3e is colorless oily liquid. The yield of product 3e was 64%.
The reaction scheme of this example is shown in the following formula:
The nuclear magnetic resonance hydrogen spectrum of the product of this example is shown in FIG. 9, and the ：1H NMR(500MHz,CDCl3)δ8.01(d,J＝7.2Hz,2H),7.59-7.57(m,3H),7.53-7.50(m,1H),7.46-7.43(m,3H),7.35(d,J＝8.0Hz,1H),7.29-7.26(m,3H),4.68(d,J＝15.1Hz,1H),4.17(d,J＝15.1Hz,1H),3.64(d,J＝14.8Hz,1H),3.46(d,J＝14.7Hz,1H),2.74(s,3H),2.40(s,3H); nuclear magnetic resonance carbon spectrum is shown in FIG. 10 ：13C NMR(101MHz,CDCl3):δ162.2,144.7,143.8,134.3,131.7,131.2,130.4,129.8,128.6,128.2,128.0,127.5,127.3,123.7,122.9,88.8,65.1,57.9,37.3,21.5.
From the above data, the synthesized product was identified to be N- ((5- (3-bromophenyl) -2-phenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide.
Example 24
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), 4-methoxy-N-methylbenzenesulfonamide 2b (80.5 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as an anode, the cathode and the anode were inserted, a magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at a constant temperature and under a constant current condition, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain a corresponding product 3f, wherein the product 3f is colorless oily liquid. The yield of product 3f was 66%.
The reaction scheme of this example is shown in the following formula:
The nuclear magnetic resonance hydrogen spectrum of the product of the example is shown in FIG. 11, and the ：1H NMR(500MHz,CDCl3)δ8.03(d,J＝7.4Hz,2H),7.63(d,J＝8.9Hz,,2H),7.51-7.48(m,1H),7.45-7.42(m,4H),7.40-7.37(m,2H),7.32-7.29(m,1H),6.94-6.91(m,2H),4.72(d,J＝15.0Hz,1H),4.21(d,J＝15.1Hz,1H),3.81(s,3H),3.70(d,J＝14.7Hz,1H),3.44(d,J＝14.7Hz,1H),2.71(s,3H); nuclear magnetic resonance carbon spectrum is shown in FIG. 12 ：13C NMR(101MHz,CDCl3):δ163.0,162.3,142.5,131.6,129.6,129.0,128.8,128.5,128.2,128.0,127.6,124.9,114.3,89.3,65.0,58.0,55.6,37.3.
From the above data, the synthesized product was identified to be N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -4-methoxy-N-methylbenzenesulfonamide.
Example 25
N- (2-phenylallyl) benzamide 1a (47.4 mg,0.2 mmol), N-methyl-4- (trifluoromethyl) benzenesulfonamide 2c (95.7 mg,200mol%,0.4 mmol), tetrabutylammonium acetate (60.3 mg,0.04 mol/L), potassium carbonate (55.3 mg,200mol%,0.4 mmol), 1, 2-dichloroethane, hexafluoroisopropanol (2:1, 5 mL) and a magnetic stirrer were sequentially added to a 5mL round bottom reaction flask with a platinum electrode as an anode, the cathode and anode were inserted, the lid was closed, the magnetic stirrer was turned on, the current was adjusted to 3mA, and electrolysis was performed for 7h at room temperature and constant current conditions, and detection was performed by TLC. After the reaction is finished, the reaction solution is extracted by ethyl acetate after removing part of the reaction solvent by vacuum concentration, then the extraction solution is concentrated in vacuum to obtain a crude product, and the crude product is separated and purified by column chromatography to obtain 3g of a corresponding product, wherein 3g of the product is colorless oily liquid. The yield of product 3g was 68%.
The reaction scheme of this example is shown in the following formula:
The nuclear magnetic resonance hydrogen spectrum of the product of the embodiment is shown in fig. 13, the ：1H NMR(500MHz,CDCl3)δ8.02(d,J＝7.0Hz,2H),7.78(d,J＝8.2Hz,2H),7.72(d,J＝8.3Hz,2H),7.52-7.49(m,1H),7.46-7.42(m,4H),7.40-7.37(m,2H),7.33-7.31(m,1H),4.64(d,J＝15.1Hz,1H),4.23(d,J＝15.1Hz,1H),3.71(d,J＝14.7Hz,1H),3.59(d,J＝14.7Hz,1H),2.78(s,3H); nuclear magnetic resonance carbon spectrum is shown in fig. 14, and the ：13C NMR(101MHz,CDCl3):δ162.4,142.1,141.3,134.4(q,J＝33.1Hz),131.7,128.8,128.6,128.14,128.12,127.9,127.4,126.3(q,J＝3.7Hz),124.9,123.2(q,J＝273.5Hz),89.2,65.2,58.0,37.2; nuclear magnetic resonance fluorine spectrum is shown in fig. 15: 19F NMR(471MHz,CDCl3 ) Delta-63.1.
From the above data, the synthesized product was identified to be N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N-methyl-4- (trifluoromethyl) benzenesulfonamide.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (10)
1. The electrochemical preparation method of the N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzenesulfonamide compound is characterized by comprising the following operation steps:
(1) Sequentially adding an N- (2-phenylallyl) benzamide compound, an N-methyl aryl sulfonamide compound, an electrolyte, alkali, an electrolytic solvent and a magnetic stirrer into a diaphragm-free electrolytic cell, inserting an anode and a cathode, continuously stirring and electrifying a reaction solution, reacting under a constant current condition, and detecting the reaction condition by TLC;
(2) After the reaction is finished, removing part of reaction solvent through vacuum concentration, then carrying out organic extraction on concentrated reaction liquid by using an organic solvent, then carrying out vacuum concentration on extract liquid to obtain a crude product, and separating and purifying the crude product to obtain a product N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound;
the structural general formula of the N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl benzene sulfonamide compound is shown as formula (I),
Wherein R, R 1 and R 2 represent electron withdrawing groups or electron donating groups, the electron withdrawing groups are selected from one of halogen and trifluoromethyl, and the electron donating groups are selected from one of methoxy, methyl and tert-butyl.
2. The electrochemical preparation method of an N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl-benzenesulfonamide compound according to claim 1, wherein the amount of the N-methyl-arylsulfonamide compound in the step (1) is 150% -250% of the molar amount of the N- (2-phenylallyl) benzamide compound.
3. The method for electrochemical preparation of N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide compound of claim 1, wherein said electrolyte of step (1) is one of tetrabutylammonium acetate, tetrabutylammonium tetrafluoroborate, tetrabutylammonium perchlorate and sodium acetate.
4. The electrochemical preparation method of an N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl-benzenesulfonamide compound of claim 1, wherein the molar concentration of said electrolyte in the electrolytic solvent in step (1) is 0.04-0.08mol/L.
5. The method for electrochemical preparation of N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide compound of claim 1, wherein said base of step (1) is one of potassium carbonate, sodium acetate, potassium phosphate, 1, 8-diazabicyclo [5.4.0] undec-7-ene and triethylamine.
6. The electrochemical preparation method of the N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl-benzenesulfonamide compound according to claim 1, wherein the amount of the base in the step (1) is 200% -250% of the molar amount of the N- (2-phenylallyl) benzamide compound.
7. The electrochemical preparation method of an N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethyl-benzenesulfonamide compound of claim 1, wherein said electrolytic solvent in step (1) is one of a mixture of 1, 2-dichloroethane and hexafluoroisopropanol and a mixture of dichloromethane and hexafluoroisopropanol.
8. The method for electrochemical preparation of N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide-based compound of claim 1, wherein said anode of step (1) is one of a carbon electrode and a reticulated vitreous carbon electrode (RVC); the cathode is one of a platinum electrode and a nickel electrode.
9. The method for electrochemical preparation of N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide-based compound according to claim 1, characterized in that the current of the reaction of step (1) is 2-4mA; the temperature of the reaction in the step (1) is room temperature; the reaction time in the step (1) is 5h 15min-10.5h.
10. The electrochemical preparation method of an N- ((2, 5-diphenyl-4, 5-dihydro-oxazol-5-yl) methyl) -N, 4-dimethylbenzenesulfonamide-based compound according to any one of claims 1-9, characterized in that the organic solvent of step (2) is ethyl acetate; and (3) separating and purifying in the step (2) by column chromatography.
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