CN110003081B - 一种多氟烷基取代的吲哚啉和四氢异喹啉的合成方法 - Google Patents
一种多氟烷基取代的吲哚啉和四氢异喹啉的合成方法 Download PDFInfo
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- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical class C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 title claims description 10
- 238000001308 synthesis method Methods 0.000 title abstract description 7
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims description 93
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 73
- 239000002904 solvent Substances 0.000 claims description 44
- -1 N-dimethyl Chemical group 0.000 claims description 43
- LQFLWKPCQITJIH-UHFFFAOYSA-N n-allyl-aniline Chemical class C=CCNC1=CC=CC=C1 LQFLWKPCQITJIH-UHFFFAOYSA-N 0.000 claims description 33
- 239000003054 catalyst Substances 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 230000002194 synthesizing effect Effects 0.000 claims description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 239000011630 iodine Substances 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- 150000008282 halocarbons Chemical class 0.000 claims description 5
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 238000010189 synthetic method Methods 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 239000010949 copper Substances 0.000 abstract description 45
- 150000002476 indolines Chemical class 0.000 abstract description 13
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 abstract description 3
- 150000001336 alkenes Chemical class 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 229910052802 copper Inorganic materials 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 193
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- 239000000047 product Substances 0.000 description 64
- 230000015572 biosynthetic process Effects 0.000 description 34
- 238000003786 synthesis reaction Methods 0.000 description 34
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 33
- 238000004293 19F NMR spectroscopy Methods 0.000 description 32
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
- 238000004440 column chromatography Methods 0.000 description 32
- 238000000605 extraction Methods 0.000 description 32
- 239000011259 mixed solution Substances 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 238000001819 mass spectrum Methods 0.000 description 31
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 31
- 239000012264 purified product Substances 0.000 description 31
- 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 description 29
- 238000000926 separation method Methods 0.000 description 20
- 238000002955 isolation Methods 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000011031 large-scale manufacturing process Methods 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 150000005826 halohydrocarbons Chemical class 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KWXGJTSJUKTDQU-UHFFFAOYSA-N 1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-heptadecafluoro-8-iodooctane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I KWXGJTSJUKTDQU-UHFFFAOYSA-N 0.000 description 1
- BULLJMKUVKYZDJ-UHFFFAOYSA-N 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-6-iodohexane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I BULLJMKUVKYZDJ-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- IRSJDVYTJUCXRV-UHFFFAOYSA-N ethyl 2-bromo-2,2-difluoroacetate Chemical compound CCOC(=O)C(F)(F)Br IRSJDVYTJUCXRV-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000004095 oxindolyl group Chemical class N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- LBUJPTNKIBCYBY-UHFFFAOYSA-N tetrahydroquinoline Natural products C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 1
- 150000003530 tetrahydroquinolines Chemical class 0.000 description 1
Classifications
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- 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
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
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Abstract
本发明提供一种多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,其通过非活化烯烃多氟烷基化合成多氟烷基吲哚啉和多氟烷基四氢异喹啉类化合物,该方法可以实现以非环原料合成吲哚啉及四氢异喹啉,同时具有良好的官能团耐受性。相对于现有技术,本发明是首例通过廉价的铜催化实现N‑烯丙基苯胺类化合物与多氟卤代烃的串联环化反应生成多氟烷基吲哚啉以及多氟烷基四氢异喹啉,本发明的合成方法简单、直接,且具有操作简单和适用底物范围广等优点。
Description
技术领域
本发明属于化学技术领域,具体地说涉及一种多氟烷基取代的吲哚啉和四氢异喹啉的合成方法。
背景技术
含氟烷基化合物在药物、农用化学品和材料中发挥着独特作用,因为氟化基团的引入可以明显改变目标分子的溶解度,代谢稳定性和生物利用度。因此,在过去几年中,化学工作者不断努力开发有效的合成含氟化合物的方法。最近,烯烃通过的双官能化引入全氟烷基(Rf)基团的方法引起了相当多的关注,并且已经成为构建官能化的含全氟烷基Rf化合物的有力策略。然而,目前的反应大都集中在活化烯烃的双官能团化,未活化烯烃的全氟烷基化双官能化的仍然是一个挑战。
吲哚类化合物,包括吲哚啉和氧化吲哚类,是生物活性天然产物和临床药物中广泛存在的有价值的结构单元。开发便捷、有效的构建吲哚骨架的方法长期受到工业界和学术界的广泛关注。与吲哚的方法相比,合成二氢吲哚支架的途径相当有限,主要局限于吲哚的去芳香化,例如:文献1:C.Zheng and S.-L.You,Chem,2016,1,830;文献2:X.-W.Liang,C.Zheng and S.-L.You,Chemistry–A European Journal,2016,22,11918;文献3:Q.Ding,X.Zhou and R.Fan,Org.Bio.Chem.,2014,12,4807.。此外,另一种通过还原氧代吲哚制备二氢吲哚酯的方法需要使用苛刻的反应条件,存在官能团容忍性差等问题,例如:文献4:L.Wang,S.Li,M.Blümel,R.Puttreddy,A.Peuronen,K.Rissanen and D.Enders,Angewandte Chemie International Edition,2017,56,8516;文献5:B.-L.Zhao and D.-M.Du,Chemical Communications,2016,52,6162;文献6:S.Kayal and S.Mukherjee,Organic&Biomolecular Chemistry,2016,14,10175;文献7:D.Du,Y.Jiang,Q.Xu,X.-Y.Tang and M.Shi,ChemCatChem,2015,7,1366.。因此,本领域亟需开发新颖且高效的合成二氢吲哚支架的方法。
2017年,袁耀锋和成佳佳课题组通过钯催化,全氟烷基卤代烃为氟烷基化试剂,实现了3-多氟烷基吲哚啉的制备,反应方程式如下所示:
这种方法的反应条件为:四三苯基膦钯为催化剂,4,5-双(二苯基膦)-9,9-二甲基氧杂蒽(Xantphos)为配体,2倍当量的碳酸铯为碱,溶剂为1,4-二氧六环,反应温度为100℃。该传统方法存在以下不足:1、四三苯基膦钯为催化剂,价格昂贵,增加工业生成的成本。2、4,5-双(二苯基膦)-9,9-二甲基氧杂蒽配体的价格更昂贵一些,在一定程度上增加工业生成的成本。3、碳酸铯作为碱,不仅价格昂贵,在空气中放置还会迅速吸湿,会进一步影响它的碱性以及反应效果。同时,大规模生产中大量碳酸铯的干燥保存也存在一定的困难。4、该反应的体系相对比较复杂,不利于工业大规模的生产。
发明内容
为解决上述问题,本发明提供了一种多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,其通过廉价铜的催化作用,实现了N-烯丙基苯胺类化合物与多氟卤代烃的串联环化反应生成多氟烷基吲哚啉以及多氟烷基四氢异喹啉。
本发明的目的是以下方式实现的:
一种多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,将N-烯丙基苯胺类化合物、催化剂、多氟卤代烃溶于溶剂中,加热反应制得多氟烷基取代的吲哚啉或者四氢异喹啉化合物,其反应方程式为:
其中,
A为C或者N;
R为甲基,甲氧基,卤素,苯基,或者杂芳基;
R1为甲基或氢;
PG为保护基团;
Rf为多氟烷基;
X为卤素;
所述催化剂为CuBr、CuCl、CuI、Cu中的任一项或至少两项混合。
所述X基团中的卤素为溴或碘;R基团中的卤素为氟、氯、溴或碘。
所述保护基团包括:氢、甲基,R2CO或R3SO2。
所述多氟烷基为C4-8全氟饱和的直链烷基,即n-C4F9、n-C6F13、n-C8F17或者CF2CO2Et中的任一种。
所述R2选自甲基、乙基、丙基、异丙基、叔丁基、n-C7H15、叔丁氧基中的任一种。
所述R3选自甲基、乙基、N,N-二甲基、苯基、对甲苯基、邻甲苯基、间氯苯基中的任一种。
所述催化剂为Cu或CuI。
所述溶剂为二甲基亚砜、N,N-二甲基甲酰胺或N,N-二甲基乙酰胺。
所述N-烯丙基苯胺类化合物与多氟卤代烃的摩尔比为1:(1.5-3.5),N-烯丙基苯胺类化合物与催化剂的摩尔比为1:(1.1-1.5)。
反应过程中反应的温度为80-130℃,反应时间3-8h。
有益效果:相对于现有技术,本发明采用廉价的铜为催化剂,通过自由基串联环化一步直接得到了多氟烷基取代的吲哚啉或者多氟烷基取代的四氢异喹啉类化合物,反应的选择性强,合成过程简单高效,反应成本低,反应操作简便,适用于工业化大规模生产;而且该反应可以兼容不同的官能团,底物的使用范围广,本发明为多氟烷基取代的吲哚啉和四氢异喹啉类化合物的合成提供了一种简便、高效的新方法。
具体实施方式
一种多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,将N-烯丙基苯胺类化合物、催化剂、多氟卤代烃溶于溶剂中,加热反应制得多氟烷基取代的吲哚啉或者四氢异喹啉化合物,其反应方程式为:
其中,
A为C或者N;
R为甲基,甲氧基,卤素,苯基,或者杂芳基;
R1为甲基或氢;
PG为保护基团;
Rf为多氟烷基;
X为卤素;
所述催化剂为CuBr、CuCl、CuI、Cu中的任一项或至少两项混合。
所述吲哚啉或四氢喹啉类化合物可以为下述的任何一种物质,在下述方程式的条件下,其分离产率百分比如下所示:
注:方程式中的反应条件为:1(0.5mmol),2(1.0mmol),Cu(0.75mmol),溶剂DMSO(3mL);所述3aa,3ba,4ba等均为底物吲哚啉或四氢喹啉类化合物的编号。
进一步地,所述X基团中的卤素为溴或碘;R基团中的卤素为氟、氯、溴或碘。
进一步地,所述保护基团包括:氢、甲基,R2CO或R3SO2。
进一步地,所述多氟烷基为C4-8全氟饱和的直链烷基,即n-C4F9、n-C6F13、n-C8F17或者CF2CO2Et中的任一种。
更进一步地,所述R2选自甲基、乙基、丙基、异丙基、叔丁基、n-C7H15、叔丁氧基中的任一种。
更进一步地,所述R3选自甲基、乙基、N,N-二甲基、苯基、对甲苯基、邻甲苯基、间氯苯基中的任一种。
优选地,所述催化剂为Cu或CuI。
进一步地,所述溶剂为二甲基亚砜、N,N-二甲基甲酰胺或N,N-二甲基乙酰胺。
进一步地,所述N-烯丙基苯胺类化合物与多氟卤代烃的摩尔比为1:(1.5-3.5),N-烯丙基苯胺类化合物与催化剂的摩尔比为1:(1.1-1.5)。
进一步地,反应过程中反应的温度为80-130℃;反应时间3-8h。
下面结合具体实施例对本发明作进一步说明:
实施例1:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲基亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率74%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.22(d,J=8.1Hz,1H),7.29-7.25(m,1H),7.14(d,J=6.1Hz,1H),7.09(td,J=7.4,1.1Hz,1H),4.10(d,J=10.9Hz,1H),3.89(dd,J=10.9,1.5Hz,1H),2.58–2.40(m,2H),2.25(s,3H),1.53(d,J=2.4Hz,3H);13C NMR(101MHz,CDCl3)δ168.81,141.28,137.98,128.98,124.27,122.10,117.49,61.50(d,J=6.2Hz),41.83,39.41(t,J=20.6Hz),26.78(d,J=3.8Hz),24.38.19F NMR(376MHz,CDCl3)δ-81.01(t,J=12.3Hz,3F),-107.46–-114.59(m,2F),-124.46–-124.58(m,2F),-125.60–-125.83(m,2F);HRMS(ESI):m/z[M+H]+calcd for C16H15F9NO:408.1004;found:408.1007。
实施例2:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率80%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.09(d,J=8.2Hz,1H),7.07(dd,J=8.4,1.6Hz,1H),6.93(s,1H),4.07(d,J=10.8Hz,1H),3.88(dd,J=10.9,1.6Hz,1H),2.52-2.40(m,2H),2.34(s,3H),2.23(s,3H),1.51(d,J=2.4Hz,3H);13C NMR(101MHz,CDCl3)δ168.45,138.98,138.15,133.97,129.44,122.62,117.23,61.64(d,J=6.3Hz),41.81,39.41(t,J=20.4Hz),26.67(d,J=3.7Hz),24.25,21.24;19F NMR(376MHz,CDCl3)δ-81.01(t,J=11.4Hz,3F),-107.82–-114.39(m,2F),-124.47–-124.56(m,2F),-125.59–-125.85(m,2F);HRMS(ESI):m/z[M+H]+calcd for C17H17F9NO:433.1161;found:433.1163。
实施例3:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率82%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.16(d,J=8.6Hz,1H),7.22(dd,J=8.6,2.2Hz,1H),7.10(d,J=2.2Hz,1H),4.11(d,J=10.9Hz,1H),3.91(dd,J=10.9,1.6Hz,1H),2.55–2.39(m,2H),2.24(s,3H),1.53(d,J=2.3Hz,3H);13C NMR(101MHz,CDCl3)δ168.74,139.97,139.73,129.09,128.94,122.52,118.50,61.57(d,J=6.2Hz),41.86,39.28(t,J=20.5Hz),26.77(d,J=3.7Hz),24.18;19F NMR(376MHz,CDCl3)δ-81.05(t,J=11.4Hz,3F),-108.02–-114.08(m,2F),-124.41–-124.55(m,2F),-125.70–-125.80(m,2F);HRMS(ESI):m/z[M+H]+calcd for C16H14ClF9NO:442.0615;found:442.0619。
实施例4:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率58%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.28(d,J=8.4Hz,1H),7.56(dd,J=8.3,1.3Hz,2H),7.51(dd,J=8.4,1.9Hz,1H),7.44(t,J=7.6Hz,2H),7.37–7.31(m,2H),4.14(d,J=10.8Hz,1H),3.94(dd,J=10.8,1.6Hz,1H),2.63–2.46(m,2H),2.27(s,3H),1.58(d,J=2.4Hz,3H);13C NMR(101MHz,CDCl3)δ168.74,140.73,140.64,138.68,137.57,128.96,127.92,127.33,127.02,120.78,117.63,61.75(d,J=6.5Hz),41.90,39.44,26.82(d,J=3.7Hz),24.31;19F NMR(376MHz,CDCl3)δ-81.02(t,J=11.4Hz,3F),-107.80–-114.22(m,2F),-124.40–-124.50(m,2F),-125.59–-125.82(m,2F);HRMS(ESI):m/z[M+H]+calcd forC22H19F9NO:484.1317;found:484.1319。
实施例5:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率71%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.51–8.36(m,2H),8.04(d,J=5.6Hz,1H),4.14(d,J=10.9Hz,1H),3.93(d,J=10.9Hz,1H),2.67–2.46(m,2H),2.27(s,3H),1.59(s,3H);13C NMR(101MHz,CDCl3)δ169.70,150.86,147.94,144.22,133.26,111.69,65.38–60.33(m),41.11,39.46(t,J=20.4Hz)27.37(d,J=3.1Hz),24.33;19F NMR(376MHz,CDCl3)δ-81.05(t,J=11.7Hz,3F),-108.16–-113.86(m,2F),-124.41–-124.51(m,2F),-125.62–-125.82(m,2F);HRMS(ESI):m/z[M+H]+calcd for C15H14F9N2O:409.0957;found:409.0958。
实施例6:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率78%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.24(d,J=8.2Hz,1H),7.19(dd,J=8.3,1.8Hz,1H),7.05(s,1H),4.19(d,J=10.8Hz,1H),3.99(d,J=10.8Hz,1H),2.63–2.53(m,4H),2.46(s,3H),1.36(t,J=7.4Hz,3H);13C NMR(101MHz,CDCl3)δ171.88,139.21,138.05,133.81,129.45,122.60,117.17,60.69(d,J=6.4Hz),41.81,39.37(t,J=20.3Hz),29.26,26.59(d,J=3.6Hz),21.22,8.84;19F NMR(376MHz,CDCl3)δ-80.90(t,J=11.5Hz,3F),-107.95–-114.06(m,2F),-124.39–-124.49(m,2F),-125.56–-125.77(m,2F);HRMS(ESI):m/z[M+H]+calcdfor C18H19F9NO:436.1317;found:436.1319。
实施例7:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率60%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.19(d,J=8.7Hz,1H),7.23(dd,J=8.7,2.2Hz,1H),7.09(d,J=2.3Hz,1H),4.10(d,J=10.8Hz,1H),3.89(d,J=10.9Hz,1H),2.50–2.40(m,4H),1.51(s,3H),1.24(t,J=7.3Hz,3H);13C NMR(101MHz,CDCl3)δ172.18,140.19,139.62,128.96,128.92,122.50,118.43,60.65(d,J=6.5Hz),41.87,39.25(t,J=20.4Hz),29.28,26.73(d,J=3.6Hz),8.73.19F NMR(376MHz,CDCl3)δ-81.01(t,J=12.0Hz,3F),-107.95–-114.06(m,2F),-124.39–-124.53(m,2F),-125.57–-125.77(m,2F);HRMS(ESI):m/z[M+H]+calcd for C17H16ClF9NO:456.0771;found:456.0776。
实施例8:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率86%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.17(d,J=8.7Hz,1H),7.22(dd,J=8.8,2.2Hz,1H),7.09(d,J=2.2Hz,1H),4.30(d,J=10.8Hz,1H),4.07(dd,J=10.8,1.6Hz,1H),2.50–2.31(m,2H),1.52(d,J=2.6Hz,3H),1.37(s,9H);13C NMR(101MHz,CDCl3)δ176.71,141.74,139.62,129.22,128.73,122.12,120.02,61.65(d,J=6.6Hz)42.53,40.28,38.14(t,J=20.6Hz),27.67,24.80,24.76.19F NMR(376MHz,CDCl3)δ-81.02(t,J=11.2Hz,3F),-107.73–-114.73(m,2F),-124.44–-124.53(m,2F),-125.38–-126.08(m,2F);HRMS(ESI):m/z[M+H]+calcdfor C19H20ClF9NO:484.1084;found:484.1087。
实施例9:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL)。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率66%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.19(d,J=8.7Hz,1H),7.22(dd,J=8.6,2.2Hz,1H),7.09(d,J=2.2Hz,1H),4.11(d,J=10.8Hz,1H),3.90(d,J=10.8Hz,1H),2.57–2.27(m,4H),1.76–1.69(m,2H),1.52(d,J=2.3Hz,3H),1.42–1.25(m,8H),0.92–0.85(m,3H);13C NMR(101MHz,CDCl3)δ171.66,140.19,139.68,128.93,122.47,118.52,60.80(d,J=6.4Hz),41.85,39.22(t,J=20.5Hz),36.03,31.82,29.41,29.26,26.65(d,J=3.7Hz),24.65,22.76,14.19.19F NMR(376MHz,CDCl3)δ-81.02(t,J=11.4Hz,3F),-107.96–-114.07(m,2F),-124.33–-124.56(m,2F),-125.57–-125.79(m,2F);HRMS(ESI):m/z[M+H]+calcd forC22H26ClF9NO:526.1554;found:526.1557。
实施例10:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率59%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.14(d,J=8.7Hz,1H),7.37(dd,J=8.6,2.0Hz,1H),7.24(d,J=2.0Hz,1H),4.10(d,J=10.8Hz,1H),3.89(d,J=10.8Hz,1H),2.57–2.30(m,4H),1.73(p,J=7.4Hz,2H),1.51(s,3H),1.42–1.25(m,8H),0.93–0.84(m,3H);13C NMR(101MHz,CDCl3)δ171.71,140.68,140.06,131.88,125.37,118.99,116.33,60.76(d,J=6.2Hz),41.84,39.26(t,J=20.5Hz),36.07,31.83,29.41,29.26,26.69(d,J=3.4Hz),24.64,22.76,14.19;19F NMR(376MHz,CDCl3)δ-80.86–-81.17(m,3F),-107.93–-114.06(m,2F),-124.37–-124.47(m,2F),-125.56–-125.77(m,2F);HRMS(ESI):m/z[M+H]+calcd forC22H26BrF9NO:570.1049;found:570.1050。
实施例11:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率84%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.80(s,1H),7.18(dd,J=8.6,2.2Hz,1H),7.06(d,J=2.2Hz,1H),4.01(d,J=11.7Hz,1H),3.84(d,J=11.9Hz,1H),2.56–2.29(m,2H),1.57(s,9H),1.48(d,J=2.3Hz,3H);13C NMR(101MHz,CDCl3)δ152.30,140.08,139.52,128.71,127.66,122.79,116.23,81.61,60.60(d,J=5.9Hz),41.08,39.39(t,J=20.5Hz),28.50,26.84(d,J=2.9Hz);19F NMR(376MHz,CDCl3)δ-81.09(t,J=10.2Hz,3F),-107.99–-114.18(m,2F),-124.46–-124.55(m,2F),-125.70–-125.83(m,2F);HRMS(ESI):m/z[M+H]+calcdfor C19H20F9NO2:500.1033;found:500.1037。
实施例12:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率62%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.14(s,1H),7.54(t,J=1.4Hz,1H),7.50–7.47(m,1H),7.41(d,J=5.0Hz,2H),7.29–7.16(m,2H),7.12(d,J=7.4Hz,1H),4.12(d,J=11.4Hz,1H),4.02–3.70(m,1H),2.66–2.29(m,2H),1.55(d,J=2.0Hz,3H);13C NMR(101MHz,CDCl3)δ167.30,140.77,138.95,138.02,134.91,130.83,130.14,128.56,127.46,125.21,124.81,122.47,117.66,62.58,41.54,38.84(t,J=20.6Hz),26.08;19F NMR(376MHz,CDCl3)δ-80.04(t,J=10.5Hz,3F),-108.63–-114.06(m,2F),-124.42–-124.52(m,2F),-125.60–-125.80(m,2F).HRMS(ESI):m/z[M+H]+calcd for C21H16ClF9NO:504.0771;found:504.0776。
实施例13:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率65%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.36(d,J=8.6Hz,1H),7.23(dd,J=8.6,2.1Hz,1H),7.14(d,J=2.1Hz,1H),3.99(dd,J=10.7,0.9Hz,1H),3.85(dd,J=10.6,1.7Hz,1H),2.93(s,3H),2.58–2.39(m,2H),1.54(d,J=2.1Hz,3H);13C NMR(101MHz,CDCl3)δ139.49,139.19,129.33,129.31,123.63,114.72,62.43(d,J=5.9Hz),41.81,38.75(t,J=20.6Hz),35.19,26.44(d,J=3.1Hz);19F NMR(376MHz,CDCl3)δ-81.06(t,J=10.9Hz,3F),-108.08–-113.61(m,2F),-124.38–-124.44(m,2F),-125.62–-125.79(m,2F).HRMS(ESI):m/z[M+H]+calcdfor C15H14ClF9NO2S:478.0285;found:478.0288。
实施例14:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率75%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.57–7.51(m,2H),7.49(d,J=1.2Hz,2H),7.44(t,J=7.6Hz,2H),7.38–7.32(m,2H),4.02(dd,J=10.6,0.9Hz,1H),3.89(dd,J=10.6,1.7Hz,1H),2.96(s,3H),2.66–2.44(m,2H),1.59(d,J=2.2Hz,3H);13C NMR(101MHz,CDCl3)δ140.43,139.83,138.41,137.70,129.05,128.31,127.54,127.04,121.94,113.87,62.58(d,J=5.9Hz),41.85,38.96,35.08,26.48(d,J=3.5Hz);19F NMR(376MHz,CDCl3)δ-81.02(t,J=11.7Hz,3F),-107.91–-113.66(m,2F),-124.32–-124.40(m,2F),-125.57–-125.74(m,2F);HRMS(ESI):m/z[M+H]+calcd for C21H19F9NO2S:520.0987;found:520.0989。
实施例15:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率78%。
1H NMR(400MHz,CDCl3)δ7.33(d,J=8.6Hz,1H),7.20(dd,J=8.5,2.1Hz,1H),7.12(d,J=2.1Hz,1H),4.09–4.01(m,1H),3.90(dd,J=10.6,1.7Hz,1H),3.14(q,J=7.4Hz,2H),2.57–2.39(m,2H),1.53(d,J=2.2Hz,3H),1.42(t,J=7.4Hz,3H);;13C NMR(101MHz,CDCl3)δ139.49,139.29,129.14,128.83,123.51,114.69,62.41(d,J=6.1Hz),44.88,41.90,38.79(t,J=20.5Hz),26.40(d,J=3.5Hz),7.84;19F NMR(376MHz,CDCl3)δ-81.06(t,J=11.3Hz,3F),-107.97–-113.79(m,2F),-124.40–-124.49(m,2F),-125.61–-125.79(m,2F);HRMS(ESI):m/z[M+H]+calcd for C16H16ClF9NO2S:492.0441;found:492.0446。
实施例16:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率74%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.57–7.50(m,2H),7.50–7.40(m,4H),7.35(d,J=7.2Hz,2H),4.09(d,J=10.6Hz,1H),3.95(dd,J=10.6,1.7Hz,1H),3.18(q,J=7.4Hz,2H),2.65–2.44(m,2H),1.58(d,J=2.2Hz,3H),1.45(t,J=7.4Hz,3H);13C NMR(101MHz,CDCl3)δ140.51,140.10,138.23,137.24,129.02,128.15,127.45,127.00,121.85,113.80,62.56(d,J=6.1Hz),44.71,41.92,39.00(t,J=20.5Hz),26.44(d,J=3.4Hz),7.89;19F NMR(376MHz,CDCl3)δ-80.03(t,J=11.3Hz,3F),-107.80–-113.84(m,2F),-124.36–-124.42(m,2F),-125.57–-125.75(m,2F);HRMS(ESI):m/z[M+H]+calcd for C22H21F9NO2S:534.1144;found:534.1147。
实施例17:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率72%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.35(d,J=1.8Hz,1H),7.00(d,J=1.8Hz,1H),4.17(d,J=10.8Hz,1H),3.90(d,J=10.7Hz,1H),3.22–3.13(m,2H),2.89–2.65(m,2H),1.65(d,J=1.6Hz,3H),1.43(t,J=7.4Hz,3H);13C NMR(101MHz,CDCl3)δ143.84,135.81,131.52,130.82,124.64,112.48,62.20(dd,J=4.9,2.7Hz),45.37,42.77,36.56,25.64(d,J=2.8Hz),7.79;19F NMR(376MHz,CDCl3)δ-81.05(t,J=12.0Hz,3F),-109.29–-113.66(m,2F),-124.51–-124.62(m,2F),-125.67–-125.80(m,2F);HRMS(ESI):m/z[M+H]+calcd forC16H15Cl2F9NO2S:526.0051;found:526.0051。
实施例18:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率71%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.58–7.51(m,2H),7.50–7.39(m,4H),7.37–7.30(m,2H),4.05(d,J=10.5Hz,1H),3.88(dd,J=10.5,1.8Hz,1H),2.94(s,6H),2.63–2.43(m,2H),1.58(d,J=2.3Hz,3H);13C NMR(101MHz,CDCl3)δ140.98,140.68,138.07,136.86,129.00,128.00,127.34,127.01,121.47,114.35,62.81(d,J=6.4Hz),41.92,39.20,39.00,38.80,38.39,26.15(d,J=3.4Hz);19F NMR(376MHz,CDCl3)δ-80.90–-81.00(m,J=10.9Hz,3F),-107.78–-114.40(m,2F),-124.40–-124.50(m,2F),-125.57–-125.78(m,2F);HRMS(ESI):m/z[M+H]+calcd for C22H22F9N2O2S:549.1253;found:549.1253。
实施例19:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率74%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.90–7.79(m,2H),7.71(d,J=8.1Hz,1H),7.56(t,J=7.4Hz,1H),7.46(dd,J=8.5,7.0Hz,2H),7.29–7.24(m,1H),7.10–6.99(m,2H),3.99–3.90(m,1H),3.80(dd,J=11.1,1.6Hz,1H),2.41–2.07(m,2H),1.26(d,J=2.5Hz,3H);13C NMR(101MHz,CDCl3)δ140.31,138.19,136.99,133.55,129.29,129.09,127.30,124.25,122.96,114.97,61.84(d,J=6.2Hz),41.75,39.07,26.21(d,J=3.6Hz);19F NMR(376MHz,CDCl3)δ-81.12(t,J=10.9Hz,3F),-107.75–-114.16(m,2F),-124.46–-124.56(m,2F),-125.69–-125.90(m,2F);HRMS(ESI):m/z[M+H]+calcd for C20H17F9NO2S:506.0831;found:506.0836。
实施例20:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率79%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.70(t,J=8.4Hz,3H),7.26(t,J=8.9Hz,3H),7.04(q,J=3.8Hz,2H),3.92(d,J=11.1Hz,1H),3.78(dd,J=11.1,1.5Hz,1H),2.46–2.02(m,5H),1.28(d,J=2.4Hz,3H);13C NMR(101MHz,CDCl3)δ144.55,140.46,138.19,134.01,129.89,129.05,127.36,124.13,122.94,115.01,61.85(d,J=6.1Hz),41.73,39.09,26.14(d,J=3.3Hz),21.55;19F NMR(376MHz,CDCl3)δ-81.12(t,J=11.3Hz,3F),-107.78–-114.19(m,2F),-124.48–-124.57(m,2F),-125.15–-125.91(m,2F);HRMS(ESI):m/z[M+H]+calcd forC21H19F9NO2S:520.0987;found:520.0988。
实施例21:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率32%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.99(d,J=8.1Hz,1H),7.52–7.39(m,2H),7.32(t,J=8.1Hz,2H),7.21(t,J=7.7Hz,1H),7.11(d,J=7.5Hz,1H),7.04(t,J=7.4Hz,1H),3.99(d,J=10.9Hz,1H),3.82(d,J=11.6Hz,1H),2.73–2.50(m,3H),2.48–2.22(m,2H),1.39(d,J=2.4Hz,3H);13C NMR(101MHz,CDCl3)δ141.05,138.26,137.93,137.32,133.40,133.11,129.62,128.96,126.50,123.88,122.88,114.89,61.58(d,J=6.3Hz),41.89,38.94(t,J=20.6Hz),25.95(d,J=3.8Hz)20.87;19F NMR(376MHz,CDCl3)δ-81.05(t,J=11.3Hz,3F),-107.76–-114.36(m,2F),-124.45–-124.52(m,2F),-125.64-125.84(m,2F);HRMS(ESI):m/z[M+H]+calcd for C21H19F9NO2S:520.0987;found:520.0988。
实施例22:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率39%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.97(dd,J=8.2,1.2Hz,1H),7.50–7.42(m,1H),7.36–7.27(m,3H),7.02–7.01(m,1H),6.89(d,J=1.7Hz,1H),3.96(dd,J=11.0,1.0Hz,1H),3.80(dd,J=11.0,1.7Hz,1H),2.61(s,3H),2.45–2.21(m,5H),1.36(d,J=2.5Hz,3H);13C NMR(101MHz,CDCl3)δ138.66,138.24,138.19,137.34,133.71,133.29,133.07,129.62,129.47,126.45,123.40,114.80,61.70(d,J=6.7Hz),41.92,38.95(t,J=20.4Hz),29.85,25.84,21.02(d,J=15.8Hz);19F NMR(376MHz,CDCl3)δ-80.97–-81.06(t,J=11.3Hz,3F),-107.70–-114.42(m,2F),-124.47–-124.56(m,2F),-125.64–-125.84(m,2F);HRMS(ESI):m/z[M+H+calcd for C22H21F9NO2S:534.1144;found:534.1147。
实施例23:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率51%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.96(dd,J=7.9,1.5Hz,1H),7.48(td,J=7.5,1.4Hz,1H),7.40(d,J=8.6Hz,1H),7.33(t,J=7.8Hz,2H),7.18(dd,J=8.6,2.1Hz,1H),7.07(d,J=2.1Hz,1H),3.97(dd,J=10.9,0.9Hz,1H),3.80(dd,J=11.0,1.7Hz,1H),2.60(s,3H),2.42–2.24(m,2H),1.37(d,J=2.4Hz,3H);13C NMR(101MHz,CDCl3)δ139.81,139.71,138.25,136.90,133.62,133.20,129.65,129.07,129.01,126.60,123.33,115.98,61.71(d,J=6.4Hz),41.98,38.78(t,J=20.5Hz),25.92(d,J=3.7Hz),20.89;19F NMR(376MHz,CDCl3)δ-81.04(t,J=11.6Hz,3F),-107.82–-114.23(m,2F),-124.42–-124.48(m,2F),-125.63–-125.82(m,2F);HRMS(ESI):m/z[M+H]+calcd for C21H18ClF9NO2S:554.0598;found:554.0599。
实施例24:
多氟取代的四氢异喹啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率25%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.99(dd,J=7.9,1.4Hz,1H),7.48(td,J=7.5,1.4Hz,1H),7.37(d,J=7.8Hz,1H),7.32(dd,J=8.0,3.8Hz,2H),7.27–7.18(m,2H),7.07–7.05(m,1H),4.52(d,J=15.1Hz,1H),4.31(d,J=15.1Hz,1H),3.67(d,J=12.5Hz,1H),3.10(d,J=12.5Hz,1H),2.67(s,3H),2.67–2.45(m,1H),2.39–2.25(m,1H),1.48(d,J=2.4Hz,3H);13CNMR(101MHz,CDCl3)δ140.39,138.32,135.35,133.36,133.11,130.84,130.56,127.62,127.23,126.85,126.49,126.38,53.72(d,J=4.3Hz),47.59,38.08(t,J=20.0Hz),37.59,25.33(d,J=4.4Hz),20.93;19F NMR(376MHz,CDCl3)δ-81.12(t,J=10.7Hz,3F),-107.72–-114.42(m,2F),-124.04–-124.24(m,2F),-125.65–-125.83(m,2F);HRMS(ESI):m/z[M+H]+calcd for C22H21F9NO2S:534.1144;found:534.1144。
实施例25:
多氟取代的多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率48%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.17(d,J=8.7Hz,1H),7.23(dd,J=8.7,2.1Hz,1H),7.17–7.10(m,1H),4.41–4.28(m,1H),3.97–3.79(m,2H),2.61(dt,J=30.9,12.7Hz,1H),2.45–2.30(m,1H),2.24(s,3H);13C NMR(101MHz,CDCl3)δ168.68,141.33,133.77,129.04,123.85,118.33,55.41(d,J=4.4Hz)36.05(t,J=21.0Hz),34.10–32.85(m),24.22;19F NMR(376MHz,CDCl3)δ-80.96(t,J=11.3Hz,3F),-111.86–-114.15(m,2F),-124.22–-124.33(m,2F),-125.75–-125.90(m,2F);HRMS(ESI):m/z[M+H]+calcd for C15H12ClF9NO:428.0458;found:428.0460。
实施例26:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率57%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ7.33(dd,J=8.6,1.5Hz,1H),7.21(dd,J=8.6,2.2Hz,1H),7.17(d,J=2.0Hz,1H),4.38–4.23(m,1H),3.90–3.75(m,2H),3.16–3.10(m,2H),2.70–2.50(m,1H),2.48–2.27(m,1H),1.46–1.34(m,3H);13C NMR(101MHz,CDCl3)δ140.74,133.81,129.25,129.00,124.79,114.87,(d,J=4.6Hz),45.53–44.40(m),35.42(t,J=21.4Hz),33.59(d,J=3.2Hz),7.85;19F NMR(376MHz,CDCl3)δ-81.06(t,J=11.3Hz,3F),-111.93–-114.14(m,2F),-124.24–-124.36(m,2F),-125.81–-125.96(m,2F);HRMS(ESI):m/z[M+H]+calcd for C15H14ClF9NO2S:478.0285;found:478.0287。
实施例27:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代己烷1.0mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率83%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.22(d,J=8.1Hz,1H),7.31–7.23(m,1H),7.14(s,1H),7.09(dd,J=7.4,1.1Hz,1H),4.10(d,J=10.8Hz,1H),3.94–3.85(m,1H),2.57–2.40(m,2H),2.25(s,3H),1.53(d,J=2.4Hz,3H);13C NMR(101MHz,CDCl3)δ168.79,141.29,138.00,128.96,124.26,122.09,117.49,61.50(d,J=6.4Hz),41.85,39.52(t,J=20.4Hz),26.75(d,J=3.7Hz),24.32;19F NMR(376MHz,CDCl3)δ-80.59–-80.89(t,J=11.3Hz,3F),-107.64–-113.92(m,2F),-121.47–-12163,(m,2F),-122.73–-122.86(m,2F),-123.53–-123.64(m,2F),-126.01–-126.18(m,2F);HRMS(ESI):m/z[M+H]+calcd for C18H15F13NO:508.0941;found:508.0947。
实施例28:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代辛烷1.0mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率50%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.22(d,J=8.1Hz,1H),7.30–7.24(m,1H),7.13(s,1H),7.09(dd,J=7.4,1.1Hz,1H),4.08(s,1H),3.94–3.85(m,1H),2.61–2.38(m,2H),2.25(s,3H),1.53(d,J=2.4Hz,3H);13C NMR(101MHz,CDCl3)δ168.79,141.29,138.01,128.97,124.26,122.09,117.50,61.51(d,J=6.3Hz),41.86,39.53(t,J=20.4Hz),26.75(d,J=3.6Hz),24.33;19F NMR(376MHz,CDCl3)δ-80.73(t,J=11.3Hz,3F).-107.63–-113.90(m,2F),-121.30–-121.86(m,2F),-122.30–-123.56(m,6F),-123.54(d,J=15.0Hz,2F),-126.07(dd,J=20.1,11.7Hz,2F).–-80.85(m,3F);HRMS(ESI):m/z[M+H]+calcd forC20H15F17NO:608.0877;found:608.0879。
实施例29:
多氟取代的吲哚啉化合物的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,二氟溴乙酸乙酯1.0mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率55%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.20(d,J=8.1Hz,1H),7.26–7.21(m,1H),7.11(d,J=1.4Hz,1H),7.05(td,J=7.5,1.1Hz,1H),4.24–4.11(m,3H),3.82(d,J=10.7Hz,1H),2.63–2.37(m,2H),2.24(s,3H),1.47(d,J=1.6Hz,3H),1.30(t,J=7.1Hz,3H);13C NMR(101MHz,CDCl3)δ164.36,144.35,138.80,134.81,132.83,130.19,129.43,128.70,128.15,128.06,127.89,126.83,124.22,55.68(d,J=3.9Hz),50.38,38.35–35.53(m)22.86;13C NMR(101MHz,CDCl3)δ168.83,164.31,163.99,163.67,141.65,137.82,128.75,124.01,122.40,118.58,117.37,116.08,113.57,63.38,61.45(d,J=4.5Hz),43.59(t,J=22.0Hz),41.71,27.08(d,J=2.6Hz),24.36,13.96;19F NMR(376MHz,CDCl3)δ-100.40–-104.22(m,2F);HRMS(ESI):m/z[M+H]+calcd for C16H20F2NO3:312.1406;found:312.1409。
实施例30:
多氟取代的四氢异喹啉的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率57%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.14(dd,J=7.8,1.5Hz,1H),7.52(td,J=7.6,1.6Hz,1H),7.40(td,J=7.5,1.2Hz,1H),7.36–7.30(m,1H),3.58(d,J=13.0Hz,1H),3.49(d,J=13.0Hz,1H),3.18(s,3H),2.57-2.42(m,1H),2.30-2.16(m,1H),1.62(d,J=2.4Hz,3H);13CNMR(101MHz,CDCl3)δ164.52,144.76,132.49,129.07,128.08,127.91,123.85,57.52(d,J=4.2Hz),37.15,36.95(t,J=20.4Hz),35.12,22.73(d,J=5.0Hz);19F NMR(376MHz,CDCl3)δ-81.04(t,J=10.9Hz,3F),-110.61–-113.28(m,2F),-124.29–-124.40(m,2F),-125.69–-125.82(m,2F);HRMS(ESI):m/z[M+H]+calcd for C16H15F9NO:408.1004;found::408.1006。
实施例31:
多氟取代的四氢异喹啉的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率25%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.18(d,J=2.4Hz,1H),7.47(dd,J=8.3,2.4Hz,1H),7.38–7.23(m,6H),4.90(d,J=14.4Hz,1H),4.65(d,J=14.4Hz,1H),3.38(q,J=13.1Hz,2H),2.35–2.09(m,2H),1.51(d,J=1.9Hz,3H);13C NMR(101MHz,CDCl3)δ163.08,142.24,136.34,134.25,132.45,129.79,129.26,128.94,128.76,128.05,126.14,55.72(d,J=3.2Hz),50.76,36.89(t,J=20.2Hz),35.76,22.85(t,J=2.9Hz);19F NMR(376MHz,Chloroform-d)δ-81.13(t,J=10.5Hz,3F),-109.91–-113.38(m,2F),-124.27–-124.37(m,2F),-125.69–-125.82(m,2F);HRMS(ESI):m/z[M+H]+calcd for C22H18ClF9NO:518.0928;found::518.0931。
实施例32:
多氟取代的四氢异喹啉的合成,其反应方程式如下:
在25mL的耐压管中加入N-烯丙基苯胺0.5mmol,Cu 0.75mmol,全氟碘代丁烷1.5mmol,溶剂二甲亚砜3.0mL。该混合液在120℃反应6h,反应结束后,用乙酸乙酯和水萃取,无水硫酸钠干燥,得到产物。产物通过柱色谱分离提纯,分离收率56%。其分离提纯后的产物的核磁共振谱以及高分辨质谱信息如下:
1H NMR(400MHz,CDCl3)δ8.23–8.18(m,1H),7.54(td,J=7.6,1.6Hz,1H),7.47–7.40(m,2H),7.37–7.32(m,2H),7.30–7.26(m,1H),7.26–7.22(m,1H),4.99(d,J=14.6Hz,1H),4.53(d,J=14.6Hz,1H),3.51–3.37(m,2H),2.43–2.07(m,2H),1.56(d,J=2.3Hz,3H);13C NMR(101MHz,CDCl3)δ164.36,144.35,138.80,134.81,132.83,130.19,129.43,128.70,128.15,128.06,127.89,126.83,124.22,55.68(d,J=3.9Hz),50.38,36.91(t,J=20.3Hz),36.09,22.86(d,J=2.0Hz);19F NMR(376MHz,CDCl3)δ-81.06(t,J=11.9Hz,3F),-110.00–-113.50(m,2F),-124.00–-124.33(m,2F),-125.54–-125.95(m,2F);HRMS(ESI):m/z[M+H]+calcd for C22H18ClF9NO:518.0928;found:518.0932。
实施例33-54的反应方程式、反应条件及分离产率如下表1所示:
表1不同催化剂、溶剂、温度、时间条件下的分离产率
注:a反应条件:1a(0.5mmol),2a(1.0mmol),催化剂(0.75mmol),溶剂3mL,反应温度120℃;
b分离产率;
cCu的用量为0.55mmol;
dCu的用量为0.6mmol;
e2a的用量为0.75mmol;
f2a的用量为1.5mmol;
g2a的用量1.75mmol。
由上表1可以看出,对于本发明的反应,当无催化剂或溶剂为DCE、MeCN、PhMe时,均不会发生反应;当催化剂为CuBr、CuCl、CuI、Cu时,均发生反应,且催化剂为Cu时,产率最高;当催化剂为Cu,溶剂为DMF、DMSO、DMAc或1,4-dioxane时,均能发生反应;而且本发明的产率可高达75%。
以上所述的仅是本发明的优选实施方式,应当指出,对于本领域的技术人员来说,在不脱离本发明整体构思前提下,还可以做出若干改变和改进,这些也应该视为本发明的保护范围,这些都不会影响本发明实施的效果和专利的实用性。
Claims (6)
2.根据权利要求1所述的多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,其特征在于:所述多氟烷基为C4-8全氟饱和的直链烷基,即n-C4F9、n-C6F13、n-C8F17或者CF2CO2Et中的任一种。
3.根据权利要求1所述的多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,其特征在于:所述R2选自甲基、乙基、丙基、异丙基、叔丁基、n-C7H15、叔丁氧基中的任一种。
4.根据权利要求1所述的多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,其特征在于:所述R3选自甲基、乙基、N,N-二甲基、苯基、对甲苯基、邻甲苯基、间氯苯基中的任一种。
5.根据权利要求1所述的多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,其特征在于:N-烯丙基苯胺类化合物与多氟卤代烃的摩尔比为1:(1.5-3.5),N-烯丙基苯胺类化合物与催化剂的摩尔比为1:(1.1-1.5)。
6.根据权利要求1所述的多氟烷基取代的吲哚啉和四氢异喹啉的合成方法,其特征在于:反应过程中反应的温度为80-130℃,反应时间3-8h。
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