CN110078655B - Method for preparing indole compound by photocatalysis - Google Patents
Method for preparing indole compound by photocatalysis Download PDFInfo
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- CN110078655B CN110078655B CN201910485455.XA CN201910485455A CN110078655B CN 110078655 B CN110078655 B CN 110078655B CN 201910485455 A CN201910485455 A CN 201910485455A CN 110078655 B CN110078655 B CN 110078655B
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- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000007146 photocatalysis Methods 0.000 title claims abstract description 9
- 230000001699 photocatalysis Effects 0.000 title claims abstract description 9
- -1 indole compound Chemical class 0.000 title claims description 66
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims description 16
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims description 14
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 50
- PGRFXXCKHGIFSV-UHFFFAOYSA-N 1,1,1,2,2,3,3,4,4-nonafluoro-4-iodobutane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)I PGRFXXCKHGIFSV-UHFFFAOYSA-N 0.000 claims abstract description 25
- 150000002475 indoles Chemical class 0.000 claims abstract description 17
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 15
- 239000000126 substance Substances 0.000 claims description 19
- 239000003960 organic solvent Substances 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 238000005286 illumination Methods 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 239000003495 polar organic solvent Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 238000010438 heat treatment Methods 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 4
- 239000011941 photocatalyst Substances 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 229910052751 metal Inorganic materials 0.000 abstract description 3
- 239000002184 metal Substances 0.000 abstract description 3
- 239000007800 oxidant agent Substances 0.000 abstract description 3
- 230000001590 oxidative effect Effects 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- 230000004913 activation Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 46
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 238000004440 column chromatography Methods 0.000 description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- 229910052799 carbon Inorganic materials 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- 238000012512 characterization method Methods 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- STRNXFOUBFLVIN-UHFFFAOYSA-N diethyl but-2-ynedioate Chemical compound CCOC(=O)C#CC(=O)OCC STRNXFOUBFLVIN-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 5
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 4
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 description 4
- 239000012295 chemical reaction liquid Substances 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 description 2
- HKOSFZXROYRVJT-UHFFFAOYSA-N 3-bromo-n-methylaniline Chemical compound CNC1=CC=CC(Br)=C1 HKOSFZXROYRVJT-UHFFFAOYSA-N 0.000 description 2
- AYVPVDWQZAAZCM-UHFFFAOYSA-N 4-bromo-n-methylaniline Chemical compound CNC1=CC=C(Br)C=C1 AYVPVDWQZAAZCM-UHFFFAOYSA-N 0.000 description 2
- XCEYKKJMLOFDSS-UHFFFAOYSA-N 4-chloro-n-methylaniline Chemical compound CNC1=CC=C(Cl)C=C1 XCEYKKJMLOFDSS-UHFFFAOYSA-N 0.000 description 2
- VLWRKVBQUANIGI-UHFFFAOYSA-N 4-fluoro-n-methylaniline Chemical compound CNC1=CC=C(F)C=C1 VLWRKVBQUANIGI-UHFFFAOYSA-N 0.000 description 2
- JFXDIXYFXDOZIT-UHFFFAOYSA-N 4-methoxy-n-methylaniline Chemical compound CNC1=CC=C(OC)C=C1 JFXDIXYFXDOZIT-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000007806 chemical reaction intermediate 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
- 238000005034 decoration Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 229930005303 indole alkaloid Natural products 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- QCIFLGSATTWUQJ-UHFFFAOYSA-N n,4-dimethylaniline Chemical compound CNC1=CC=C(C)C=C1 QCIFLGSATTWUQJ-UHFFFAOYSA-N 0.000 description 2
- FRCFWPVMFJMNDP-UHFFFAOYSA-N n-propan-2-ylaniline Chemical compound CC(C)NC1=CC=CC=C1 FRCFWPVMFJMNDP-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 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
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000007243 oxidative cyclization reaction Methods 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
Abstract
The invention relates to the technical field of synthesis of organic intermediates, and provides a method for preparing indole compounds by photocatalysis. The method provides energy by irradiation of light, and performs light-promoted cyclization reaction under the activation of perfluoroiodobutane, so that a target object is obtained, the reaction condition is mild, high-temperature heating is not required in the process, a photocatalyst is not required to be added, any metal reagent and any oxidant are not required to be added, the reaction process is stable, and the control is easy.
Description
Technical Field
The invention relates to the technical field of synthesis of organic intermediates, in particular to a method for preparing indole compounds by photocatalysis.
Background
In recent years, some naturally occurring and synthetic indoles have been found to be anti-aids, anti-microbial, anti-cancer and anti-diabetic drugs. Such as reserpine (anti-hypertensive) and the antitumor antibiotic-staphylococcin. In addition, indole is considered to be a multifunctional drug core, a compound with complex biological activity. Because indole alkaloids have various structural characteristics and broad-spectrum biological activity, the indole alkaloids not only serve as a lead compound, but also serve as a fully synthetic target, thereby arousing great interest. Such drugs are also intermediates for the anti-inflammatory and anti-analgesic activity of the drugs Sumengla and doxycycline.
Meanwhile, with the increasing status of indole and its derivatives, researchers at home and abroad have developed some methods for synthesizing indole compounds. For example, palladium-catalyzed N-oxidative cyclization reaction is used for synthesizing 1,3 alkylaryl tertiary amine-disubstituted indole (the reaction formula is shown as formula 1). The reaction is carried out by adding Pd catalyst and Cu catalyst for catalytic reaction, and the reaction is carried out under high temperature condition, and the reaction process is harsh and difficult to control.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for synthesizing indole compounds by photocatalysis, which does not require heating, does not require adding a photocatalyst, a metal reagent and an oxidant, can prepare the indole compounds by illumination, and has the advantages of mild reaction conditions and easy control.
In order to achieve the above object, the present invention provides the following technical solutions:
a method for preparing indole compounds by photocatalysis comprises the following steps:
mixing an amine compound, alkyne ester, perfluoroiodobutane, an alkaline substance and an organic solvent to obtain an alkaline reaction solution;
and (3) illuminating the alkaline reaction solution, and performing cyclization reaction at normal temperature to obtain the indole compound.
Preferably, the structural formula of the amine compound is R1-NHR2Said R is1Is phenyl, alkyl substituted phenyl, alkoxy substituted phenyl, halogen substituted phenyl or heterocycle substituted phenyl; r2Is methyl, ethyl or propyl.
Preferably, the alkyne ester has the structural formula of R3OOC-C≡C-COOR3Said R is3Is ethyl or methyl.
Preferably, the amount ratio of the amine compound to the alkyne ester is 1 (1-2).
Preferably, the amount ratio of the amine compound to the perfluoroiodobutane is 1 (1-3).
Preferably, the ratio of the volume of the organic solvent to the amount of the amine compound is 1L: 0.1 to 0.2 mol.
Preferably, the organic solvent is a polar organic solvent.
Preferably, the pH value of the alkaline reaction liquid is 8-11.
Preferably, the wavelength of the light source of the illumination is 200-1000 nm.
Preferably, the cyclization reaction time is 6-24 h.
The invention provides a method for synthesizing indole compounds by photocatalysis, which comprises the steps of mixing an amine compound, alkyne ester, perfluoroiodobutane, an alkaline substance and an organic solvent to obtain an alkaline reaction solution, then carrying out light irradiation on the alkaline reaction solution, and carrying out cyclization reaction at normal temperature to obtain the indole compounds. In the invention, an amine compound is used as an electron donor, an alkyne ester is used as an electron acceptor, the amine compound is coupled with the alkyne ester in a reaction solution to form an EDA compound, and the EDA compound can be used as a photocatalyst to catalyze the reaction; under the irradiation of light, the EDA compound is dissociated to generate N-methylamine radical negative ions and alkyne ester radical positive ions, and then the reaction intermediate N, N-disubstituted alkyne ester amine is obtained through coupling, and the intermediate is cyclized under the alkaline environment due to the fact that hydrogen atoms on the ortho position of amino are activated by perfluoroiodobutane, and the target product is obtained. The preparation method provided by the invention provides energy by irradiation of light, can obtain a target object under the condition of not adding any photocatalyst, metal reagent and oxidant, and has the advantages of stable reaction process, mild condition and easy control.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a product obtained in example 1 of the present invention;
FIG. 2 is a nuclear magnetic resonance carbon spectrum of the product obtained in example 1 of the present invention;
FIG. 3 is a NMR chart of a product obtained in example 2 of the present invention;
FIG. 4 is a nuclear magnetic resonance carbon spectrum of the product obtained in example 2 of the present invention;
FIG. 5 is a NMR chart of a product obtained in example 3 of the present invention;
FIG. 6 is the NMR spectrum of the product obtained in example 3 of the present invention;
FIG. 7 is a NMR chart of a product obtained in example 4 of the present invention;
FIG. 8 is the NMR spectrum of the product obtained in example 4 of the present invention;
FIG. 9 is a NMR chart of a product obtained in example 5 of the present invention;
FIG. 10 is the NMR spectrum of the product obtained in example 5 of the present invention;
FIG. 11 is a NMR chart of a product obtained in example 6 of the present invention;
FIG. 12 is a NMR spectrum of a product obtained in example 6 of the present invention;
FIG. 13 is a NMR chart of the product obtained in example 7 of the present invention;
FIG. 14 is a NMR spectrum of a product obtained in example 7 of the present invention;
FIG. 15 is a NMR chart of a product obtained in example 8 of the present invention;
FIG. 16 is a NMR spectrum of a product obtained in example 8 of the present invention;
FIG. 17 is a NMR chart of a product obtained in example 9 of the present invention;
FIG. 18 is a NMR spectrum of a product obtained in example 9 of the present invention;
FIG. 19 is a NMR spectrum of a product obtained in example 10 of the present invention;
FIG. 20 is a NMR spectrum of a product obtained in example 10 of the present invention;
FIG. 21 is a NMR chart of a product obtained in example 11 of the present invention;
FIG. 22 is a NMR spectrum of a product obtained in example 11 of the present invention;
FIG. 23 is a NMR chart of a product obtained in example 12 of the present invention;
FIG. 24 shows the NMR spectrum of the product obtained in example 12 of the present invention.
Detailed Description
The invention provides a method for preparing indole compounds by photocatalysis, which comprises the following steps:
mixing an amine compound, alkyne ester, perfluoroiodobutane, a basic substance and an organic solvent to obtain a basic reaction solution;
and (3) illuminating the alkaline reaction solution, and performing cyclization reaction at normal temperature to obtain the indole compound.
The method mixes an amine compound, alkyne ester, perfluoroiodobutane, an alkaline substance and an organic solvent to obtain an alkaline reaction solution. In the invention, the structural formula of the amine compound is R1-NHR2Said R is1Preferably phenyl, alkyl-substituted phenyl, alkoxy-substituted phenyl, halogen-substituted phenyl or heterocycle-substituted phenyl; the alkyl-substituted phenyl is preferably an alkyl-substituted phenyl with 1-5 carbon atoms, and is further preferably p-methylphenyl or m-methylphenyl; the alkoxy-substituted phenyl group is preferably a methoxy-substituted phenyl group, and more preferably a p-methoxyphenyl group; the halogen-substituted phenyl is preferably F-substituted phenyl, Cl-substituted phenyl or Br-substituted phenyl, and is further preferably p-fluorophenyl, p-chlorophenyl, p-bromophenyl, m-chlorophenyl or m-bromophenyl; the heterocyclic group in the heterocycle-substituted phenyl group is preferably a quinoline ring or a piperonyl ring; the R is2Preferably methyl, ethyl or propyl.
In the present invention, the amine compound is particularly preferably N-methylaniline, 4-fluoro-N-methylaniline, 4-chloro-N-methylaniline, 4-bromo-N-methylaniline, 4-methyl-N-methylaniline, 4-methoxy-N-methylaniline, 3-bromo-N-methylaniline, N-ethylaniline, N-isopropylaniline, piperonylamine, or 1,2,3, 4-tetrahydroquinoline.
In the invention, the alkyne ester has a structural formula of R3OOC-C≡C-COOR3Wherein R is3Preferably ethyl or methyl, and in the present invention, the alkyne ester is particularly preferably diethyl acetylenedicarboxylate or dimethyl acetylenedicarboxylate.
In the present invention, the organic solvent is preferably a polar organic solvent, more preferably one or more of dimethyl sulfoxide, N-dimethylformamide, toluene, ethanol, acetonitrile and dichloromethane, and more preferably acetonitrile.
In the invention, the amount ratio of the amine compound to the alkyne ester is preferably 1 (1-2); more preferably 1: 1.5.
in the invention, the amount ratio of the amine compound to the perfluoroiodobutane is preferably 1 (1-3); more preferably 1: 1.5.
in the present invention, the ratio of the volume of the organic solvent to the amount of the substance of the amine compound is preferably 1L: 0.1 to 0.2mol, more preferably 1L: 0.1 mol.
In the present invention, the pH of the alkaline reaction solution is preferably 8 to 11, and more preferably 9 to 10. In the present invention, the basic substance is preferably an inorganic basic substance and/or an organic basic substance; the inorganic alkaline substance is preferably one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate; further preferably sodium hydroxide or potassium hydroxide; the organic basic substance is preferably an organic amine, and more preferably triethylamine. In the present invention, when the alkaline substance is a mixture of two or more components, the amount ratio of each component in the mixture is not particularly limited; in the present invention, the alkaline substance may be added in an amount that the pH of the alkaline reaction solution can meet the requirement, and in a specific embodiment of the present invention, the specific addition amount may be determined according to the kind of the alkaline substance. The addition method of the alkaline substance is not limited in any way, and the addition method known to those skilled in the art can be adopted. The invention utilizes alkaline substances to adjust the pH of the raw material reaction liquid to a proper alkaline state, can promote the cyclization of the raw material compound, and provides favorable conditions for obtaining the target product.
In the invention, the amine compound, the alkyne ester, the perfluoroiodobutane, the basic substance and the organic solvent are mixed at normal temperature, and the mixing mode is not limited in any way, and the mixing mode known by the person skilled in the art is adopted. The sources of the amine compound, the alkyne ester, the perfluoroiodobutane, the basic substance and the organic solvent are not required to be any special requirements, and the commercially available products well known to those skilled in the art can be adopted.
After obtaining the alkaline reaction liquid, the invention performs light irradiation on the alkaline reaction liquid, and performs cyclization reaction at normal temperature to obtain the indole compound. In the present invention, the wavelength of the light source for the illumination is preferably 200 to 1000nm, and more preferably 300 to 800 nm. The light source is not limited in any way, and the light source with the wavelength can be provided. In the invention, the time of the cyclization reaction is preferably 6-24 h, and more preferably 8-20 h.
According to the invention, an amine compound is used as an electron donor, an alkyne ester is used as an electron acceptor, the amine compound and the alkyne ester are coupled in a reaction solution to form an EDA compound (structural formula is shown in formula a), under the irradiation of light, the EDA compound is dissociated to generate N-methylamine radical negative ions and alkyne ester radical positive ions, then the reaction intermediate N, N-disubstituted alkyne ester amine is obtained through coupling, and the perfluoro iodobutane activates hydrogen atoms on ortho-positions of amino groups of the amine compound, so that the amine compound is cyclized in an alkaline environment to obtain a target product. In the invention, the alkaline condition provides necessary basic conditions for the cyclization reaction, the illumination provides the energy required for the cyclization reaction, and the indole compound target product can be obtained without heating under the normal temperature condition by matching with the selection of raw materials, so that the whole reaction condition is mild and is easy to control. In addition, the preparation method of the indole compound provided by the invention has good adaptability to raw materials, and can be used for preparing indole compounds with different substituents.
After the cyclization reaction is completed, the present invention preferably performs a purification treatment on the mixture after the cyclization reaction. In the present invention, the purification treatment is preferably column chromatography. In the present invention, the eluent for the column chromatography is preferably a mixed solvent of petroleum ether and ethyl acetate; in the invention, the volume ratio of petroleum ether to ethyl acetate in the mixed solvent is preferably 1-30: 1, more preferably 5 to 20: 1, more preferably 5: 1. the specific method for carrying out the column chromatography in the present invention is not particularly limited, and may be performed in a manner known to those skilled in the art. According to the invention, petroleum ether and ethyl acetate are used as eluent to purify the mixed solution after cyclization reaction, so that the indole compound with higher purity can be obtained.
In the present invention, the structural formula of the indole compound is preferably as shown in formula I:
in the formula I, R1And R2Preferably R in amine compound in preparation process1And R2Remain uniform, R3With R of the alkyne ester in the preparation process3Keeping the same is not described herein.
In the present invention, the specific structure of formula I may be, but is not limited to, the following structure:
in the invention, the purity of the indole compound obtained after purification is preferably 98.5-99.9%, and more preferably 99-99.9%.
The embodiments of the present invention will be described in detail with reference to the following examples, but they should not be construed as limiting the scope of the present invention.
Example 1
Adding 0.1mmol of N-methylaniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1ml of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 365nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 70 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, wherein a nuclear magnetic resonance hydrogen spectrogram and a nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 1 and fig. 2, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3,ppm)：δ8.15-8.13(d,J＝8Hz,3H),7.37-7.35(m,2H),7.33-7.27(m,1H),4.51-4.46(q,J＝8Hz,2H),4.41-4.36(q,J＝8Hz,2H),3.82(s,3H),1.45-1.42(t,J＝8Hz,3H),1.41-1.39(t,J＝8Hz,3H).
13C NMR(100MHz,CDCl3,ppm)：δ＝164.2,162.9,136.8,135.0,125.4,124.3,122.5,122.3,110.1,108.0,62.3,60.2,31.3,14.4,14.1.
MS(EI,70eV)：m/z(％)＝275(M+),243,216,185,159,129,102,77.
according to the data and spectrogram analysis, the obtained product is a target product, and the structure of the 2-iminothiazolidine-4-ketone compound is shown as the formula (1):
example 2
Adding 0.1mmol of 4-fluoro-N-methylaniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 385nm source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 62 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 3 and 4, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3,ppm)：δ7.81-7.78(dd,J＝4Hz,1H),7.31-7.28(m,1H),7.13-7.08(m,1H),4.52-4.46(q,J＝8Hz,2H),4.41-4.35(q,J＝8Hz,2H),3.82(s,3H),1.45-1.42(t,J＝4Hz,3H),1.42-1.39(t,J＝4Hz,3H).
13C NMR(100MHz,CDCl3,ppm)：δ163.7,162.5,160.7,158.3,136.5,133.3,126.1(J＝8Hz),113.3(J＝8Hz),111.1(J＝8Hz),107.6,62.5,60.3,31.6,14.4,14.1.
MS(EI,70eV)：m/z(％)＝309(M+),264,236,209,191.
the structure of the obtained product is deduced according to the data as shown in the formula (2):
example 3
Adding 0.1mmol of 4-chloro-N-methylaniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 400nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 78 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 5 and 6, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3,ppm)δ8.13-8.12(m,1H),7.31-7.30(m,2H),4.52-4.47(q,J＝8Hz,2H),4.41-4.36(q,J＝8Hz,2H),3.82(s,3H),1.46-1.43(t,J＝8Hz,3H),1.42-1.39(t,J＝8Hz,3H)；
13C NMR(100MHz,CDCl3,ppm)δ163.6,162.4,136.2,135.1,128.5,126.3,124.8,121.9,111.2,107.5,62.5,60.4,31.6,14.4,14.0；
Ms(EI):m/z＝309,264,236,209,191；
the structure of the obtained product is deduced according to the data as shown in the formula (3):
example 4
Adding 0.1mmol of 4-bromo-N-methylaniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 520nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 56% and the purity of 99.9%.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 7 and 8, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3,ppm)δ8.29-8.28(d,J＝4Hz,1H),7.46-7.43(m,1H),7.26-7.23(m,1H),4.52-4.46(q,J＝8Hz,2H),4.41-4.36(q,J＝8Hz,2H),3.81(s,3H),1.45-1.43(t,J＝4Hz,3H),1.42-1.39(t,J＝8Hz,3H)；
13C NMR(100MHz,CDCl3,ppm)δ163.6,162.4,136.0,135.4,127.4,126.9,125.0,116.1,111.6,107.4,62.5,60.4,31.5,14.4,14.0；
Ms(EI):m/z＝353,309,280,253,237,209；
the structure of the obtained product is deduced according to the data as shown in the formula (4):
example 5
Adding 0.1mmol of 4-methyl-N-methylaniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 465nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 44% and the purity of 99.9%.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 9 and fig. 10, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3,ppm)δ7.92-7.92(m,1H),7.24(s,1H),7.19-7.17(m,1H),4.50-4.45(q,J＝8Hz,2H),4.41-4.36(q,J＝8Hz,2H),3.81(s,3H),2.48(s,3H),1.45-1.42(t,J＝8Hz,3H),1.41-1.39(t,J＝4Hz,3H)；
13C NMR(100MHz,CDCl3,ppm)δ164.3,162.9,135.3,134.7,132.1,126.1,125.7,121.8,109.7,107.6,62.2,60.1,31.4,21.6,14.4,14.1；
Ms(EI):m/z＝289,244,216,189,171,145；
the structure of the obtained product is deduced according to the data as shown in the formula (5):
example 6
Adding 0.1mmol of 4-methoxy-N-methylaniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 365nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 63 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 11 and 12, and the structural characterization data are as follows:
1H NMR(400MHz,d6-DMSO,ppm)δ7.58-7.56(d,J＝8Hz,1H),7.46-7.45(d,J＝4Hz,1H),7.04-7.01(dd,J＝8Hz,1H),4.44-4.38(q,J＝8Hz,2H),4.29-4.24(q,J＝8Hz,2H),3.81(s,3H),3.79(s,3H),1.37-1.33(t,J＝8Hz,3H),1.33-1.29(t,J＝8Hz,3H)；
13C NMR(100MHz,CDCl3,ppm)δ164.2,162.8,156.2,134.9,131.9,126.3,115.4,111.0,107.3,102.9,62.2,60.1,55.7,31.5,14.4,14.1；
Ms(EI):m/z＝305,290,260,232,218,187；
the structure of the obtained product is deduced according to the data as shown in the formula (6):
example 7
Adding 0.1mmol of 3-bromo-N-methylaniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a light source with the wavelength of 425nm, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 55 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 13 and 14, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3)：δ＝7.39-7.34(m,2H),δ＝7.23-7.19(t,J＝4Hz,1H),4.47-4.41(q,J＝8Hz,2H),4.41-4.36(q,J＝8Hz,2H),4.05(s,3H),1.45-1.42(t,J＝8Hz,3H),1.41-1.37(t,J＝8Hz,3H).
13C NMR(100MHz,CDCl3)：δ＝171.3,153.4,149.1,147.8,142.3,129.2,124.7,121.0,110.5,109.5,39.1,32.6.
MS(EI,70eV)：m/z(％)＝353(M+),310,280,253,236,209.
the structure of the obtained product is deduced according to the data as shown in the formula (7):
example 8
Adding 0.1mmol of N-ethyl aniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 415nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 57 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 15 and 16, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3,ppm)δ8.16-8.14(m,1H),7.40-7.38(m,1H),7.36-7.32(m,1H),7.31-7.27(m,1H),4.51-4.46(q,J＝8Hz,2H),4.41-4.36(q,J＝8Hz,2H),4.30-4.25(q,J＝8Hz,2H),1.45-1.39(m,9H)；
13C NMR(100MHz,CDCl3,ppm)δ164.2,163.0,135.6,134.7,125.6,124.2,122.5,122.5,110.1,107.7,62.3,60.2,40.2,15.5,14.5,14.1；
Ms(EI):m/z＝289,244,214,170,143,114；
the structure of the obtained product is deduced according to the data as shown in the formula (8):
example 9
Adding 0.1mmol of N-isopropyl aniline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a light source of 565nm, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 25 percent and the purity of 99.9 percent.
The structure of the obtained product was characterized, and the nmr hydrogen spectrum and the nmr carbon spectrum were shown in fig. 17 and 18, respectively. The structural characterization data of the resulting product are shown below:
1H NMR(400MHz,CDCl3,ppm)δ8.21-8.18(m,1H),7.54-7.52(m,1H),7.32-7.27(m,2H),4.73-4.66(m,1H),4.52-4.46(q,J＝8Hz,2H),4.40-4.34(q,J＝8Hz,2H),1.67(s,2H),1.65(s,3H),1.45-1.38(m,6H)；
13C NMR(100MHz,CDCl3,ppm)δ166.6,164.1,164.0,136.0,134.7,126.2,123.5,122.6,122.2,111.9,62.4,60.0,50.2,21.6,14.4,14.0；
Ms(EI):m/z＝303,258,228,211,188,170；
the structure of the obtained product is deduced according to the data as shown in the formula (9):
example 10
Adding 0.1mmol of piperonylamine, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 365nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 65 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 19 and fig. 20, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3,ppm)δ7.47(s,1H),6.78(s,1H),6.00(s,2H),4.47-4.41(q,J＝8Hz,2H),4.39-4.34(q,J＝8Hz,2H),3.78(s,3H),1.43-1.37(m,6H)；
13C NMR(100MHz,CDCl3,ppm)δ164.3,162.5,147.1,145.3,132.6,132.2,119.9,109.4,101.2,100.4,90.5,62.0,60.3,31.8,14.4,14.1；
Ms(EI):m/z＝319,274,246,219,172；
the structure of the obtained product is deduced according to the data as shown in the formula (10):
example 11
Adding 0.1mmol of 1,2,3, 4-tetrahydroquinoline, 0.15mmol of diethyl acetylenedicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 465nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 50 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 21 and 22, and the structural characterization data are shown as follows:
1H NMR(400MHz,CDCl3,ppm)δ7.86-7.84(d,J＝8Hz,1H),7.20-7.16(t,J＝8Hz,1H),7.06-7.04(d,J＝8Hz,1H),4.49-4.44(q,J＝8Hz,2H),4.42-4.36(q,J＝8Hz,2H),4.30-4.28(t,J＝4Hz,2H),3.01-2.98(t,J＝8Hz,2H),2.27-2.22(m,2H),1.44-1.39(m,6H)；
13C NMR(100MHz,CDCl3,ppm)δ164.2,163.0,135.6,134.7,125.6,124.2,122.5,122.5,110.1,107.7,62.3,60.2,40.2,15.5,14.5,14.1；
Ms(EI):m/z＝301,255,228,200,183,155；
the structure of the obtained product is deduced according to the data as shown in the formula (11):
example 12
Adding 0.1mmol of N-methylaniline, 0.15mmol of acetylene dimethyl dicarboxylate, 0.15mmol of perfluoroiodobutane, 0.1mmol of triethylamine and 1mL of acetonitrile into a reaction tube, stirring and reacting for 12 hours under the irradiation of a 465nm light source, separating and purifying by column chromatography after the reaction is finished, wherein the volume ratio of petroleum ether to ethyl acetate in eluent of the column chromatography is 5: 1, obtaining the purified target product with the yield of 53 percent and the purity of 99.9 percent.
The structure of the obtained product is characterized, the nuclear magnetic resonance hydrogen spectrogram and the nuclear magnetic resonance carbon spectrogram are respectively shown in fig. 23 and 24, and the structural characterization data are as follows:
1H NMR(400MHz,CDCl3,ppm)δ8.13-8.11(d,J＝8Hz,1H),7.38-7.36(m,2H),7.32-7.28(m,1H),4.02(s,3H),3.93(s,3H),3.84(s,3H)；
13C NMR(100MHz,CDCl3,ppm)δ164.6,163.3,136.8,134.7,125.3,124.5,122.6,122.4,110.2,108.1,53.0,51.5,31.4；
Ms(EI):m/z＝247,216,186,157,129；
the structure of the obtained product is deduced according to the data as shown in formula (12):
according to the characterization results of the embodiments 1 to 12, a series of indole compounds can be obtained by the preparation method provided by the invention; the preparation method provided by the invention provides the required energy for the raw materials by utilizing the irradiation of light, can obtain the target product under the alkaline condition, does not need heating in the reaction, has mild reaction condition and is easy to control; in addition, the preparation method provided by the invention has the advantages that the raw materials are easy to obtain, and the raw material cost is reduced; and the prepared indole compound has higher purity, so the preparation method provided by the invention has higher market popularization value.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (8)
1. A method for preparing indole compounds by photocatalysis is characterized by comprising the following steps:
mixing an amine compound, alkyne ester, perfluoroiodobutane, an alkaline substance and an organic solvent to obtain an alkaline reaction solution;
performing illumination on the alkaline reaction solution, and performing cyclization reaction at normal temperature to obtain indole compounds; the structural formula of the indole compound is shown as the formula I:
in formula I: r1Is H, alkyl, alkoxy, halogen or heterocyclyl, R2Is methyl, ethyl or propyl, R3Is ethyl or methyl;
the structural formula of the amine compound is as follows:
wherein R is1Is H, alkyl, alkoxy, halogen or heterocyclyl; r2Is methyl, ethyl or propyl;
the structural formula of the alkyne ester is R3OOC-C≡C-COOR3Said R is3Is ethyl or methyl.
2. The method according to claim 1, wherein the amount of the amine compound to the alkyne ester is 1 (1-2).
3. The method according to claim 1, wherein the amount of the amine compound to the perfluoroiodobutane is 1 (1-3).
4. The process according to claim 1, characterized in that the ratio of the volume of organic solvent to the amount of substance of amine compound is 1L: 0.1 to 0.2 mol.
5. The method according to claim 1 or 4, characterized in that the organic solvent is a polar organic solvent.
6. The method according to claim 1, wherein the pH of the alkaline reaction solution is 8 to 11.
7. The method according to claim 1, wherein the illumination has a light source wavelength of 200 to 1000 nm.
8. The method according to claim 1, wherein the cyclization reaction time is 6-24 hours.
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