CN108976243A - 通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法 - Google Patents
通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法 Download PDFInfo
- Publication number
- CN108976243A CN108976243A CN201810967990.4A CN201810967990A CN108976243A CN 108976243 A CN108976243 A CN 108976243A CN 201810967990 A CN201810967990 A CN 201810967990A CN 108976243 A CN108976243 A CN 108976243A
- Authority
- CN
- China
- Prior art keywords
- oxoindole
- hydroxy
- synthetic method
- benzyl alcohol
- spiral shell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 title claims abstract description 29
- CQRYARSYNCAZFO-UHFFFAOYSA-N o-hydroxybenzyl alcohol Natural products OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 title claims abstract description 20
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 238000010189 synthetic method Methods 0.000 title claims abstract description 17
- FJSKXQVRKZTKSI-UHFFFAOYSA-N 2,3-dimethylfuran Chemical compound CC=1C=COC=1C FJSKXQVRKZTKSI-UHFFFAOYSA-N 0.000 title claims description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- GSNUFIFRDBKVIE-UHFFFAOYSA-N 2,5-dimethylfuran Chemical compound CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 8
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 239000010949 copper Substances 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical group OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 4
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims description 3
- 239000005711 Benzoic acid Substances 0.000 claims description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- 229910052802 copper Inorganic materials 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- QUJLPICXDXFRSN-UHFFFAOYSA-N scandium;trifluoromethanesulfonic acid Chemical compound [Sc].OS(=O)(=O)C(F)(F)F QUJLPICXDXFRSN-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- UTEFBSAVJNEPTR-RGEXLXHISA-N loprazolam Chemical compound C1CN(C)CCN1\C=C/1C(=O)N2C3=CC=C([N+]([O-])=O)C=C3C(C=3C(=CC=CC=3)Cl)=NCC2=N\1 UTEFBSAVJNEPTR-RGEXLXHISA-N 0.000 claims description 2
- 229960003019 loprazolam Drugs 0.000 claims description 2
- 230000004044 response Effects 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 claims 2
- WRLRISOTNFYPMU-UHFFFAOYSA-N [S].CC1=CC=CC=C1 Chemical compound [S].CC1=CC=CC=C1 WRLRISOTNFYPMU-UHFFFAOYSA-N 0.000 claims 1
- 150000004682 monohydrates Chemical class 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 7
- 238000005899 aromatization reaction Methods 0.000 abstract description 5
- 239000007848 Bronsted acid Substances 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 3
- 238000007115 1,4-cycloaddition reaction Methods 0.000 abstract description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 239000003863 metallic catalyst Substances 0.000 abstract 1
- 230000009257 reactivity Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 72
- 239000000126 substance Substances 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- 239000002028 Biomass Substances 0.000 description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 238000006352 cycloaddition reaction Methods 0.000 description 5
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000005698 Diels-Alder reaction Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000003547 Friedel-Crafts alkylation reaction Methods 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960004217 benzyl alcohol Drugs 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 2
- 239000000446 fuel Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- MIOPJNTWMNEORI-XVKPBYJWSA-N (R)-camphorsulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)C[C@H]1C2(C)C MIOPJNTWMNEORI-XVKPBYJWSA-N 0.000 description 1
- -1 Alkyl sulfonic acid Chemical compound 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- BHAROVLESINHSM-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1.CC1=CC=CC=C1 BHAROVLESINHSM-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D491/12—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 three hetero rings
- C07D491/20—Spiro-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
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明涉及合成螺‑色满‑4,3′‑氧化吲哚化合物的方法，含氧化吲哚邻羟基苄醇与2,5‑二甲基呋喃在布朗斯特酸的存在下，首次实现了含氧化吲哚o‑QMs与富电子芳香烃进行分子间去芳香化的[4+2]环加成反应。本发明提供的合成方法，室温下即可反应，反应条件温和，通过一步反应合成螺‑色满‑4,3′‑氧化吲哚化合物，底物普适性好，无需金属催化剂，操作方便，经济高效；本发明方法的反应活性高，产率高达85％，原料转化完全；产物分离方便，且反应具有绿色经济性，对环境友好。
Description
技术领域
本发明属于化学合成技术领域，本发明涉及通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法。
背景技术
生物质能源广泛存在于自然界中，是一种重要的可再生能源储备。近年来，随着化石燃料的消耗及人类社会对可持续发展的迫切需求，生物质的转化成为一大研究热点。其中，2,5-二甲基呋喃(2,5-DMF)，是一种重要的生物质平台分子，通常作为第二代燃料及重要的化学工业原料。在2,5-DMF的转化中，通常作为双烯体发生串联的Diels-Alder反应、脱水反应用于制备甲苯。尽管该方法实现了生物质源2,5-DMF的有效转化，但是其作为双烯体的反应模式相对有限。因此，发展2,5-DMF新的反应模式，尤其是作为亲双烯体构建药物活性分子，变得具有挑战性及迫切性。
螺环氧化吲哚，尤其是螺-色满-n-3′-氧化吲哚，存在于天然产物及药物活性分子中，因此对于此类化合物的化学合成至关重要。然而，目前合成螺-色满-n-3′-氧化吲哚的报道非常有限。近年来，合成螺-色满-3-3′-氧化吲哚的方法主要是通过氧杂-Micheal-Micheal反应(Angew.Chem.,Int.Ed.,2016,55,12104；Org.Lett.,2016,18,2387；Org.Biomol.Chem.,2014,12,574；Adv.Synth.Catal.,2014,356,579；Org.Lett.,2013,15,4062)。然而，目前，合成螺-色满-4-3′-氧化吲哚的合成方案只有一个。
2017年，胡文浩课题组发展了一种过渡金属铑催化的α-苯酚酮与重氮氧化吲哚的反应合成螺-色满-4-3′-氧化吲哚化合物。虽然该方法取得了不错的效果(Adv.Synth.Catal.,2017,359,58-63)。但是，一方面，需要用价格昂贵的过渡金属催化剂，如铑，这样不仅会提高生产成本，而且从最终产品中除去有毒的重金属催化剂变得非常困难；另一方面，酮及重氮原料都需要合成，且相对复杂，因此这类合成策略的原子经济性不高。因此，发展无金属，且原料简单易得的方法构建这种化合物非常必要。
为了实现生物质平台分子到高附加值化学品的转化，解决有机合成方法学中存在的问题，构建具有生物活性的重要化合物，需要发展一种通过生物质源2,5-二甲基呋喃与含氧化吲哚邻羟基苄醇的去芳香化环加成策略合成螺-色满-4,3′-氧化吲哚化合物的新方法。
发明内容
本发明的目的在于提供一种通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法。本发明操作简单实用，产率好，且反应具有绿色经济性，对环境友好。
本发明所提供的合成方法，具体为：
含氧化吲哚邻羟基苄醇与2,5-二甲基呋喃，在催化剂作用下，反应生成所述螺-色满-4,3′-氧化吲哚。
上述螺-色满-4,3′-氧化吲哚为式Ⅰ、式Ⅱ所示化合物任意一种：
其中
式Ⅰ、式Ⅱ中，虚线表示任选的单键；
R1选自甲基、卤素中任意一种；并且
R2选自C1-C3烷基、苄基、环丙基、甲基环丙基、烯丙基、炔丙基中任意一种；并且
R3选自卤素。
上述含氧化吲哚邻羟基苄醇为式Ⅲ、式Ⅳ所示化合物任意一种：
其中
式Ⅲ、式Ⅳ中，虚线表示任选的单键；
R1选自甲基、卤素中任意一种；并且
R2选自C1-C3烷基、苄基、环丙基、甲基环丙基、烯丙基、炔丙基中任意一种；并且
R3选自卤素。
上述催化剂为布朗斯酸或路易斯酸，具体为三氟甲磺酸、对甲苯磺酸一水合物、甲烷磺酸、三氟乙酸、樟脑磺酸、联萘酚磷酸酯、苯甲酸、乙酸、三氟甲磺酸钪、三氟甲磺酸铜中任意一种。
上述反应在溶剂中进行，溶剂为甲苯、1,2-二氯乙烷、二氯甲烷、四氢呋喃、乙腈中任意一种。
上述催化剂的用量为5mol％-20mol％。
上述含氧化吲哚邻羟基苄醇与2,5-二甲基呋喃的摩尔比为1:3。
上述溶剂的用量为每摩尔含氧化吲哚邻羟基苄醇添加10L溶剂。
上述反应在25℃条件下进行。
本发明提供了式Ⅰ、式Ⅱ所示化合物的合成方法，具体包括以下步骤：
将含氧化吲哚邻羟基苄醇加入溶剂中，按比例向溶剂中加入2,5-二甲基呋喃，最后加入催化剂，搅拌反应，通过薄层色谱法检测反应情况，反应完毕纯化，制得螺-色满-4,3′-氧化吲哚。
本发明涉及的化合物可以以一种或者多种立体异构体的形式存在。各种异构体包括对映异构体、非对映异构体、几何异构体。这些异构体包括这些异构体的混合物均在本发明的保护范围内。
本发明的技术方案取得了如下有益效果：含氧化吲哚邻羟基苄醇在布朗斯特酸催化下脱水生成中含氧化吲哚邻亚甲基苯醌(o-QMs)中间体，然后与2,5-二甲基呋喃发生逆电子需求的氧杂D-A反应生成中间体，然后该中间体在酸性条件下水解开环生成螺-色满-4,3′-氧化吲哚化合物。
2,5-二甲基呋喃作为一个稳定的芳香化合物，作为环加成反应中的亲双烯体较为少见，并且2,5-二甲基呋喃与醇通过傅-克烷基化反应进行简单取代是热力学上的优势反应；本发明的合成策略克服了反应机理上存在的重大困难，即2,5-二甲基呋喃与醇直接取代的竞争反应，实现了2,5-二甲基呋喃去芳香化的逆电子需求的D-A环加成。此外，o-QMs是一种重要的构建模块，其参与的逆电子需求-杂Diels-Alder(IED-HDA)反应是合成复杂的天然产物及药物分子的方法之一。然而，有限的o-QMs种类及亲双烯体种类严重限制了该方法的发展及应用。本发明的合成方法首次实现了含氧化吲哚o-QMs与富电子芳香烃进行分子间去芳香化的[4+2]环加成反应。
本发明发展了一种布朗斯特酸催化的生物质源2,5-二甲基呋喃与含氧化吲哚邻羟基苄醇的去芳香化环加成反应合成螺-色满-4,3′-氧化吲哚化合物。该方法实现了2,5-二甲基呋喃作为亲双烯体，含氧化吲哚o-QMs作为新的构建模块，解决了目前合成策略中含氧化吲哚的o-QMs与2,5-DMF的傅-克烷基化反应的干扰，通过有机催化分子间环加成反应合成螺-色满-4,3′-氧化吲哚化合物。该方法反应条件温和，通过一步反应合成螺-色满-4,3′-氧化吲哚化合物，底物普适性好，底物取代基可以是吸电子基或供电子基，且取代基的位置对反应产率没有明显的影响。本发明为生物质平台分子2,5-二甲基呋喃转化为药物活性分子提供了实验依据和新思路，对生物质领域及o-QMs领域具有非常重要的意义。
具体实施方式
通过以下实施例提供的具体实施方案，对本发明的上述内容进行进一步详细说明，对于本研究领域的技术人员而言，不应将此理解为本发明上述主题的范围仅限于以下实例；凡基于本发明上述内容所实现的技术均属于本发明的范围。
下面实施例中所使用的实验方法如无特殊说明，均为常规方法；下述实施例中所用的试剂、材料、仪器等，如无特殊说明，均可从商业途径得到。
实施例1
取0.1mmol含氧化吲哚邻羟基苄醇于反应瓶中，依次加入1mL溶剂，0.3mmol的2,5-二甲基呋喃，最后再加入催化剂。控制体系温度25℃，持续搅拌，通过薄层色谱板点样跟踪反应至原料反应完全。
待反应完成后，使用硅胶柱进行分离纯化，将纯化后的产品旋蒸得目标产物。
利用上述反应式，设立16组平行试验组，使用不同的催化剂、溶剂和反应时间。催化剂分别为三氟甲磺酸TfOH、对甲苯磺酸一水合物p-TSA·H2O、甲烷磺酸MeSO3H、三氟乙酸TFA、樟脑磺酸(-)-CSA、联萘酚磷酸酯PA、苯甲酸PhCO2H、乙酸AcOH、三氟甲磺酸钪Sc(OTf)3、三氟甲磺酸铜Cu(OTf)2。溶剂分别为甲苯toluene、1,2-二氯乙烷DCE、二氯甲烷DCM、四氢呋喃THF、乙腈MeCN。试验组具体使用的催化剂、溶剂种类和浓度如表1所示：
表1.含氧化吲哚邻羟基苄醇与2,5-二甲基呋喃反应产率表
注：产率为分离产率，dr>20:1。
根据以上平行试验结果分析，大部分布朗斯特酸及路易斯酸可以得到目标产物。如11所示，当使用10mol％p-TSA·H2O做催化剂，DCE作溶剂，室温下反应2h能以85％获得目标产物。
下列实施例2-19中，按照实施例1的操作步骤，反应体系中，原料含氧化吲哚邻羟基苄醇与2,5-二甲基呋喃分别为0.1mmol、0.3mmol，在10mol％p-TSA·H2O催化下，以1mLDCE作溶剂，25℃下持续搅拌反应至原料反应完全。
实施例2
产物：化学式：C28H25NO6
分子量：471.1682
结构式：
产率：85％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.36–7.25(m,7H),7.05(t,J＝7.3Hz,1H),6.85(d,J＝7.7Hz,1H),6.49(s,1H),5.82(d,J＝10.0Hz,2H),5.73(s,1H),5.61–5.54(m,1H),4.94(d,J＝15.5Hz,1H),4.89(d,J＝15.4Hz,1H),2.95(dd,J＝15.5,8.8Hz,1H),2.90(s,1H),2.81(d,J＝15.5Hz,1H),2.34(s,3H),0.90(s,3H)；13C NMR(125MHz,CDCl3)δ206.53,176.99,149.15,147.99,143.84,142.77,135.75,130.00,128.96,128.86,127.82,127.60,127.40,123.32,112.51,108.86,107.09,101.27,98.95,73.91,69.51,58.52,44.19,43.32,30.45,18.89.
实施例3
产物：化学式：C29H27NO6
分子量：485.1838
结构式：
产率：82％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.33–7.24(m,5H),7.16(s,1H),7.06(d,J＝7.9Hz,1H),6.73(d,J＝7.8Hz,1H),6.48(s,1H),5.82(d,J＝13.5Hz,2H),5.74(s,1H),5.58(d,J＝8.2Hz,1H),4.91(d,J＝15.5Hz,1H),4.87(d,J＝15.9Hz,1H),3.05–2.70(m,3H),2.34(s,3H),2.27(s,3H),0.90(s,3H)；13C NMR(125MHz,CDCl3)δ206.61,176.93,149.13,147.94,142.72,141.45,135.86,132.85,129.95,129.29,128.81,128.25,127.75,127.38,112.70,108.60,107.20,101.25,98.90,73.95,69.49,58.59,44.18,43.35,30.39,21.20,18.90.
实施例4
产物：化学式：C28H24FNO6
分子量：489.1588
结构式：
产率：85％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.29(dd,J＝24.0,7.1Hz,5H),7.18–7.08(m,1H),6.96(t,J＝8.4Hz,1H),6.80–6.71(m,1H),6.49(s,1H),5.84(d,J＝9.1Hz,2H),5.71(s,1H),5.61–5.49(m,1H),4.92(d,J＝15.7Hz,1H),4.88(d,J＝16.0Hz,1H),3.03(s,1H),2.94(dd,J＝15.5,8.4Hz,1H),2.83(d,J＝15.7Hz,1H),2.34(s,3H),0.91(s,3H)；13C NMR(125MHz,CDCl3)δ206.42,176.77,159.34(d,J＝239.8Hz),149.10,148.15,142.89,139.72,135.46,131.76(d,J＝8.5Hz),128.94,127.95,127.36,115.79(d,J＝25.3Hz),115.38(d,J＝23.5Hz),112.06,109.27(d,J＝8.1Hz),106.84,101.36,99.04,73.86,69.48,58.86,44.34,43.19,30.52,18.94.
实施例5
产物：化学式：C28H24FNO6
分子量：489.1588
结构式：
产率：80％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.31(dt,J＝21.1,6.9Hz,5H),7.14(d,J＝7.2Hz,1H),7.06(t,J＝9.7Hz,1H),7.03–6.97(m,1H),6.48(s,1H),5.83(d,J＝7.1Hz,2H),5.69(s,1H),5.60–5.50(m,1H),5.10(d,J＝15.1Hz,1H),5.01(d,J＝15.1Hz,1H),3.00–2.87(m,2H),2.80(d,J＝15.6Hz,1H),2.33(s,3H),0.84(s,3H)；13C NMR(125MHz,CDCl3)δ206.42,176.76,149.06,148.13,147.13(d,J＝242.8Hz),142.84,136.86,132.89(d,J＝2.4Hz),130.57(d,J＝8.4Hz),128.63,127.77,127.74,123.77(d,J＝6.3Hz),123.57(d,J＝3.1Hz),117.07(d,J＝19.3Hz),112.18,106.94,101.33,99.00,73.71,69.49,58.80,45.79(d,J＝5.0Hz),43.21,30.49,18.82.
实施例6
产物：化学式：C28H24ClNO6
分子量：505.1292
结构式：
产率：33％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.33(d,J＝10.2Hz,5H),7.20(t,J＝7.5Hz,1H),7.02(d,J＝8.0Hz,1H),6.79(d,J＝7.6Hz,1H),6.52(s,1H),5.90(s,1H),5.84(d,J＝6.3Hz,2H),5.35(d,J＝9.2Hz,1H),4.97–4.86(m,2H),3.08–2.90(m,2H),2.67(d,J＝15.5Hz,1H),2.32(s,3H),0.93(s,3H)；13C NMR(125MHz,CDCl3)δ206.10,176.65,149.64,148.23,145.89,143.32,135.24,133.06,130.09,128.99,128.05,127.57,126.55,125.30,109.95,107.68,106.28,101.39,99.25,74.74,72.31,60.41,44.56,43.00,30.51,18.65.
实施例7
产物：化学式：C28H24ClNO6
分子量：505.1292
结构式：
产率：78％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.37–7.21(m,7H),6.75(d,J＝8.2Hz,1H),6.48(s,1H),5.84(d,J＝9.5Hz,2H),5.71(s,1H),5.58–5.49(m,1H),4.94–4.84(m,2H),3.03(s,1H),2.93(dd,J＝15.7,8.4Hz,1H),2.82(d,J＝15.7Hz,1H),2.33(s,3H),0.90(s,3H)；13C NMR(125MHz,CDCl3)δ206.40,176.60,149.11,148.17,142.88,142.33,135.31,131.76,128.95,128.93,128.66,128.08,127.98,127.35,111.92,109.71,106.86,101.36,99.03,73.85,69.46,58.70,44.28,43.16,30.53,18.93.
实施例8
产物：化学式：C28H24ClNO6
分子量：505.1292
结构式：
产率：80％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.31(dt,J＝17.7,7.4Hz,6H),7.03(d,J＝8.0Hz,1H),6.84(s,1H),6.48(s,1H),5.83(d,J＝9.2Hz,2H),5.71(s,1H),5.58–5.46(m,1H),4.91(d,J＝15.5Hz,1H),4.85(d,J＝15.5Hz,1H),3.03(s,1H),2.93(dd,J＝15.6,8.4Hz,1H),2.82(d,J＝15.8Hz,1H),2.33(s,3H),0.88(s,3H)；13C NMR(125MHz,CDCl3)δ206.42,176.95,149.12,148.14,144.96,142.89,135.20,134.78,129.01,128.69,128.44,128.04,127.35,123.26,112.01,109.37,106.83,101.35,99.01,73.85,69.45,58.26,44.29,43.20,30.52,18.89.
实施例9
产物：化学式：C28H24BrNO6
分子量：549.0787
结构式：
产率：35％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.40–7.27(m,5H),7.20(d,J＝7.8Hz,1H),7.11(t,J＝7.8Hz,1H),6.83(d,J＝7.5Hz,1H),6.52(s,1H),5.91(s,1H),5.84(d,J＝3.7Hz,2H),5.33(d,J＝9.4Hz,1H),4.91(s,2H),2.96(d,J＝16.5Hz,2H),2.67(d,J＝15.5Hz,1H),2.32(s,3H),0.92(s,3H)；13C NMR(125MHz,CDCl3)δ206.06,176.71,149.96,148.23,146.07,143.42,135.22,130.21,128.99,128.50,128.32,128.06,127.58,122.05,110.10,108.22,106.47,101.40,99.24,74.91,72.52,60.77,44.49,42.96,30.48,18.67.
实施例10
产物：化学式：C28H24BrNO6
分子量：549.0787
结构式：
产率：83％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.49(s,1H),7.37(d,J＝8.3Hz,1H),7.29(dt,J＝15.8,7.0Hz,5H),6.71(d,J＝8.3Hz,1H),6.47(s,1H),5.82(d,J＝8.1Hz,2H),5.71(s,1H),5.56–5.45(m,1H),4.95–4.83(m,2H),3.10(s,1H),2.93(dd,J＝15.8,8.5Hz,1H),2.81(d,J＝15.4Hz,1H),2.32(s,3H),0.89(s,3H)；13C NMR(125MHz,CDCl3)δ206.38,176.49,149.10,148.19,142.90,142.82,135.28,132.10,131.84,130.78,128.96,128.00,127.35,116.09,111.91,110.22,106.87,101.38,99.04,73.85,69.48,58.66,44.26,43.16,30.54,18.94.
实施例11
产物：化学式：C28H24BrNO6
分子量：549.0787
结构式：
产率：75％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.47(d,J＝7.8Hz,1H),7.36–7.20(m,6H),6.93(t,J＝7.6Hz,1H),6.46(s,1H),5.82(d,J＝12.2Hz,2H),5.76(s,1H),5.55–5.49(m,1H),5.47(d,J＝16.3Hz,1H),5.34(d,J＝16.2Hz,1H),3.09(s,1H),2.90(dd,J＝15.5,8.7Hz,1H),2.77(d,J＝15.7Hz,1H),2.30(s,3H),0.87(s,3H)；13C NMR(125MHz,CDCl3)δ206.48,177.84,149.12,148.12,142.82,141.34,137.26,135.04,133.36,128.55,127.26,127.09,126.64,124.40,112.23,106.96,102.03,101.34,98.96,73.74,69.52,58.05,45.02,43.20,30.40,18.94.
实施例12
产物：化学式：C22H21NO6
分子量：395.1369
结构式：
产率：83％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.38(t,J＝7.6Hz,1H),7.33(d,J＝7.3Hz,1H),7.10(t,J＝7.4Hz,1H),6.93(d,J＝7.7Hz,1H),6.47(s,1H),5.83(s,1H),5.79(s,1H),5.72(s,1H),5.57–5.49(m,1H),3.24(s,3H),2.93(dd,J＝15.5,8.7Hz,1H),2.87(s,1H),2.80(d,J＝15.6Hz,1H),2.33(s,3H),0.85(s,3H)；13C NMR(125MHz,CDCl3)δ206.53,176.85,149.15,147.93,144.68,142.65,129.91,129.07,127.48,123.33,112.32,107.81,107.21,101.25,98.88,73.80,69.40,58.66,43.36,30.44,26.57,18.62.
实施例13
产物：化学式：C23H23NO6
分子量：409.1525
结构式：
产率：84％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.37(t,J＝7.5Hz,1H),7.33(d,J＝7.3Hz,1H),7.08(t,J＝7.3Hz,1H),6.94(d,J＝7.7Hz,1H),6.47(s,1H),5.81(d,J＝18.9Hz,2H),5.72(s,1H),5.59–5.47(m,1H),3.93–3.80(m,1H),3.70(dt,J＝13.1,6.6Hz,1H),2.93(dd,J＝15.3,8.9Hz,1H),2.87(s,1H),2.79(d,J＝15.5Hz,1H),2.33(s,3H),1.26(t,J＝6.6Hz,3H),0.86(s,3H)；13C NMR(125MHz,CDCl3)δ206.56,176.43,149.17,147.91,143.70,142.71,130.20,129.01,127.72,123.10,112.42,107.93,107.10,101.24,98.90,73.87,69.43,58.48,43.35,34.96,30.39,18.55,12.47.
实施例14
产物：化学式：C24H23NO6
分子量：421.1525
结构式：
产率：72％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.38(t,J＝7.5Hz,1H),7.29(d,J＝7.3Hz,1H),7.19(d,J＝7.7Hz,1H),7.09(t,J＝7.3Hz,1H),6.46(s,1H),5.81(d,J＝16.8Hz,2H),5.68(s,1H),5.55–5.45(m,1H),2.92(dd,J＝15.3,9.0Hz,1H),2.83(s,1H),2.77(d,J＝15.5Hz,1H),2.68(d,J＝2.8Hz,1H),2.33(s,3H),1.09(d,J＝6.1Hz,2H),0.87(s,2H),0.83(s,3H)；13CNMR(125MHz,CDCl3)δ206.55,177.47,149.13,147.89,145.00,142.68,129.42,128.95,127.36,123.19,112.46,109.17,107.04,101.23,98.90,73.77,69.43,58.50,43.35,30.33,22.42,18.48,6.39,6.34.
实施例15
产物：化学式：C25H25NO6
分子量：435.1682
结构式：
产率：80％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.36(d,J＝6.7Hz,1H),7.31(d,J＝6.4Hz,1H),7.07(s,1H),7.01(d,J＝6.9Hz,1H),6.45(s,1H),5.91–5.66(m,3H),5.51(d,J＝5.1Hz,1H),3.81–3.39(m,2H),3.05–2.86(m,2H),2.77(d,J＝15.0Hz,1H),2.32(s,3H),1.21(s,1H),0.88(s,3H),0.50(s,2H),0.37(s,2H)；13C NMR(125MHz,CDCl3)δ206.65,176.94,149.19,147.86,144.32,142.67,130.13,128.96,127.70,123.03,112.58,108.26,107.16,101.23,98.84,73.91,69.40,58.51,44.46,43.35,30.39,18.66,9.59,3.78,3.68.
实施例16
产物：化学式：C24H23NO6
分子量：421.1525
结构式：
产率：76％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.35(t,J＝7.4Hz,2H),7.09(t,J＝7.4Hz,1H),6.92(d,J＝7.8Hz,1H),6.47(s,1H),5.87–5.76(m,3H),5.73(s,1H),5.58–5.50(m,1H),5.32–5.20(m,2H),4.48–4.38(m,1H),4.28(dd,J＝8.8,7.3Hz,1H),2.98–2.86(m,2H),2.79(d,J＝15.6Hz,1H),2.33(s,3H),0.89(s,3H)；13C NMR(125MHz,CDCl3)δ206.53,176.57,149.16,147.96,143.83,142.71,131.05,129.93,128.96,127.58,123.27,117.99,112.38,108.70,107.10,101.25,98.90,73.83,69.43,58.54,43.34,42.61,30.40,18.76.
实施例17
产物：化学式：C24H21NO6
分子量：419.1369
结构式：
产率：82％，dr>20:1
1H NMR(500MHz,CDCl3)δ7.41(t,J＝7.5Hz,1H),7.35(d,J＝7.2Hz,1H),7.13(t,J＝8.1Hz,2H),6.47(s,1H),5.81(d,J＝18.6Hz,2H),5.74(s,1H),5.49(d,J＝4.8Hz,1H),4.63(d,J＝17.6Hz,1H),4.39(d,J＝17.7Hz,1H),2.93(dd,J＝15.8,8.7Hz,1H),2.89(s,1H),2.80(d,J＝15.3Hz,1H),2.33(s,3H),2.23(s,1H),0.87(s,3H)；13C NMR(125MHz,CDCl3)δ206.44,176.00,149.18,148.04,142.71,129.76,129.05,127.61,123.64,112.07,108.78,107.20,101.27,98.90,76.55,73.83,72.36,69.60,58.55,43.30,30.48,29.51,18.53
实施例18
产物：化学式：C31H27NO4
分子量：477.1940
结构式：
产率：80％，dr>20:1
1H NMR(500MHz,CDCl3)δ8.18(d,J＝7.0Hz,1H),7.70(d,J＝6.6Hz,1H),7.52–7.45(m,2H),7.33–7.21(m,8H),7.05(t,J＝7.4Hz,1H),6.90(d,J＝7.8Hz,1H),6.34(d,J＝8.5Hz,1H),5.82(d,J＝9.1Hz,1H),4.98(d,J＝15.5Hz,1H),4.92(d,J＝15.3Hz,1H),3.15(dd,J＝15.0,9.5Hz,1H),2.93(d,J＝15.1Hz,1H),2.87(s,1H),2.45(s,3H),0.99(s,3H)；13C NMR(125MHz,CDCl3)δ206.49,176.83,149.49,144.03,135.79,133.77,129.97,128.97,128.85,127.83,127.68,127.46,127.37,126.89,126.00,125.43,124.89,123.30,121.79,121.66,114.62,108.89,74.49,69.64,58.68,44.24,43.43,30.37,18.86.
实施例19
产物：化学式：C31H26ClNO4
分子量：511.1550
结构式：
产率：76％，dr>20:1
1H NMR(500MHz,CDCl3)δ8.20(d,J＝8.0Hz,1H),8.10(d,J＝8.1Hz,1H),7.59(t,J＝7.0Hz,1H),7.55(d,J＝7.6Hz,1H),7.32(t,J＝8.4Hz,7H),7.07(t,J＝7.1Hz,1H),6.91(d,J＝7.6Hz,1H),6.43(s,1H),5.86–5.71(m,1H),5.04–4.90(m,2H),3.14(dd,J＝14.9,9.3Hz,1H),2.95(d,J＝11.5Hz,2H),2.43(s,3H),0.97(s,3H)；13C NMR(125MHz,CDCl3)δ206.30,176.46,148.75,143.93,135.63,130.82,129.32,129.21,128.92,127.92,127.90,127.64,127.43,126.76,125.96,125.08,124.60,124.23,123.55,122.22,115.08,109.12,74.65,69.54,58.46,44.31,43.30,30.47,19.04.
以上所述，仅是本发明的较佳实施例而已，并非是对本发明作其它形式的限制，任何熟悉本专业的技术人员可能利用上述揭示的技术内容加以变更或改型为等同变化的等效实施例。但是凡是未脱离本发明技术方案内容，依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与改型，仍属于本发明技术方案的保护范围。
Claims (10)
1.通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法，其特征在于：
含氧化吲哚邻羟基苄醇与2,5-二甲基呋喃，在催化剂作用下，反应生成所述螺-色满-4,3′-氧化吲哚。
2.根据权利要求1所述的合成方法，其特征在于：
上述螺-色满-4,3′-氧化吲哚为式Ⅰ、式Ⅱ所示化合物任意一种：
其中
式Ⅰ、式Ⅱ中，虚线表示任选的单键；
R1选自甲基、卤素中任意一种；并且
R2选自C1-C3烷基、苄基、环丙基、甲基环丙基、烯丙基、炔丙基中任意一种；并且
R3选自卤素。
3.根据权利要求1或2所述的合成方法，其特征在于：
上述含氧化吲哚邻羟基苄醇为式Ⅲ、式Ⅳ所示化合物任意一种：
其中
式Ⅲ、式Ⅳ中，虚线表示任选的单键；
R1选自甲基、卤素中任意一种；并且
R2选自C1-C3烷基、苄基、环丙基、甲基环丙基、烯丙基、炔丙基中任意一种；并且
R3选自卤素。
4.根据权利要求3所述的合成方法，其特征在于：所述催化剂为三氟甲磺酸、对甲苯磺酸一水合物、甲烷磺酸、三氟乙酸、樟脑磺酸、联萘酚磷酸酯、苯甲酸、乙酸、三氟甲磺酸钪、三氟甲磺酸铜中任意一种。
5.根据权利要求4所述的合成方法，其特征在于：所述反应在溶剂中进行，溶剂为甲苯、1,2-二氯乙烷、二氯甲烷、四氢呋喃、乙腈中任意一种。
6.根据权利要求5所述的合成方法，其特征在于：所述催化剂的用量为5mol％-20mol％。
7.根据权利要求6所述的合成方法，其特征在于：所述含氧化吲哚邻羟基苄醇与2,5-二甲基呋喃的摩尔比为1:3。
8.根据权利要求7所述的合成方法，其特征在于：所述溶剂的用量为每摩尔含氧化吲哚邻羟基苄醇添加10L溶剂。
9.根据权利要求8所述的合成方法，其特征在于：所述反应在25℃条件下进行。
10.根据权利要求1-9任一项所述的合成方法，其特征在于：具体包括以下步骤：
将含氧化吲哚邻羟基苄醇加入溶剂中，按比例向溶剂中加入2,5-二甲基呋喃，最后加入催化剂，搅拌反应，通过薄层色谱法检测反应情况，反应完毕纯化，制得所述螺-色满-4,3′-氧化吲哚。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810967990.4A CN108976243B (zh) | 2018-08-23 | 2018-08-23 | 通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810967990.4A CN108976243B (zh) | 2018-08-23 | 2018-08-23 | 通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108976243A true CN108976243A (zh) | 2018-12-11 |
| CN108976243B CN108976243B (zh) | 2020-03-03 |
Family
ID=64547000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810967990.4A Expired - Fee Related CN108976243B (zh) | 2018-08-23 | 2018-08-23 | 通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108976243B (zh) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113173925A (zh) * | 2021-04-30 | 2021-07-27 | 浙江大学 | 一种苯并氧杂卓并吲哚衍生物及其制备方法 |
| CN115160331A (zh) * | 2022-08-04 | 2022-10-11 | 青岛农业大学 | 一种氧化吲哚螺烯丙基取代色满骨架及其制备方法 |
| CN115403588A (zh) * | 2022-08-04 | 2022-11-29 | 青岛农业大学 | 氧化吲哚螺二苯并[b,f]氧杂环辛烷类化合物及其制备方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006110917A2 (en) * | 2005-04-11 | 2006-10-19 | Xenon Pharmaceuticals Inc. | Spiro-oxindole compounds and their uses as therapeutic agents |
| WO2008060789A2 (en) * | 2006-10-12 | 2008-05-22 | Xenon Pharmaceuticals Inc. | Use of spiro-oxindole compounds as therapeutic agents |
| WO2010045251A2 (en) * | 2008-10-17 | 2010-04-22 | Xenon Pharmaceuticals, Inc. | Spiro-oxindole compounds and their use as therapeutic agents |
| WO2012049555A1 (en) * | 2010-10-13 | 2012-04-19 | Lupin Limited | Spirocyclic compounds as voltage-gated sodium channel modulators |
-
2018
- 2018-08-23 CN CN201810967990.4A patent/CN108976243B/zh not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006110917A2 (en) * | 2005-04-11 | 2006-10-19 | Xenon Pharmaceuticals Inc. | Spiro-oxindole compounds and their uses as therapeutic agents |
| WO2008060789A2 (en) * | 2006-10-12 | 2008-05-22 | Xenon Pharmaceuticals Inc. | Use of spiro-oxindole compounds as therapeutic agents |
| WO2010045251A2 (en) * | 2008-10-17 | 2010-04-22 | Xenon Pharmaceuticals, Inc. | Spiro-oxindole compounds and their use as therapeutic agents |
| WO2012049555A1 (en) * | 2010-10-13 | 2012-04-19 | Lupin Limited | Spirocyclic compounds as voltage-gated sodium channel modulators |
Non-Patent Citations (3)
| Title |
|---|
| ANTOINETTE E. NIBBS ET AL.: "Access to Spirocyclized Oxindoles and Indolenines via Palladium-Catalyzed Cascade Reactions of Propargyl Carbonates with 2-Oxotryptamines and Tryptamines", 《J. ORG. CHEM.》 * |
| NAVEEN KUMAR ET AL.: "Catalyst-Free Synthesis of 3-Aryl-3-hydroxy-2-oxindole Derivatives by Using Water as the Solvent: Experimental and DFT Studies", 《ASIAN J. ORG. CHEM.》 * |
| YAO-BIN SHEN ET AL.: "Dearomative [4+2] Cycloaddition of Oxindole-Embedded ortho-Quinone Methides with 2,5-Dialkylfurans", 《ADV. SYNTH. CATAL》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113173925A (zh) * | 2021-04-30 | 2021-07-27 | 浙江大学 | 一种苯并氧杂卓并吲哚衍生物及其制备方法 |
| CN115160331A (zh) * | 2022-08-04 | 2022-10-11 | 青岛农业大学 | 一种氧化吲哚螺烯丙基取代色满骨架及其制备方法 |
| CN115403588A (zh) * | 2022-08-04 | 2022-11-29 | 青岛农业大学 | 氧化吲哚螺二苯并[b,f]氧杂环辛烷类化合物及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108976243B (zh) | 2020-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Suggs et al. | Synthesis of a chiral rhodium alkyl via metal insertion into an unstrained CC bond and use of the rate of racemization at carbon to obtain rhodium-carbon bond dissociation energy | |
| Kaida et al. | Synthesis of Thieno [3, 2-b] benzofurans by Palladium-catalyzed Intramolecular C–H/C–H Coupling | |
| CN108976243A (zh) | 通过二甲基呋喃与含氧化吲哚邻羟基苄醇合成螺-色满-4,3′-氧化吲哚的合成方法 | |
| Zhang et al. | A Two‐Step Sequence to Ethyl α‐Fluorocyclopropanecarboxylates Through MIRC Reaction of Ethyl Dichloroacetate and Highly Regioselective Fluorination | |
| Huang et al. | A facile and highly stereoselective synthesis of (2E)-,(2E, 4E)-unsaturated amides and related natural products | |
| CN110305054B (zh) | 一种双取代苯乙烯类衍生物的制备方法 | |
| CN112142694A (zh) | 一种多取代四氢呋喃与四氢吡喃双烯体类化合物及其制备方法 | |
| CN112457276B (zh) | 一种合成丁苯酞的方法 | |
| Yao et al. | Lewis Acid Catalyzed Cascade Reactions of 1, 6‐Diynes and 1, 6‐Enynes with Vinylidenecyclopropanes | |
| Zhao et al. | A novel multicomponent reaction to synthesize substituted furo [3, 2-c] chromenes via a Pd-catalyzed cascade process | |
| CN103724151B (zh) | 一种合成9-芳基芴化合物的方法 | |
| CN109651385A (zh) | 一种吡喃[3,2-a]咔唑类化合物的制备方法 | |
| Liu et al. | Yb (OTf) 3-Promoted ZnCl2-Catalyzed Conia-Ene Reaction of Linear β-Alkynic β-Dicarbonyls | |
| CN112979402A (zh) | 一种苯并[a]蒽的工业化生产方法 | |
| Lin et al. | Highly efficient synthesis of 3-indolyl-substituted phthalides via Friedel–Crafts reactions in water | |
| Kimura et al. | A novel procedure for the preparation of zinc reagents: a practical synthesis of (+)-biotin | |
| CN113548965B (zh) | 一种1,4烯炔类化合物的制备方法 | |
| CN106518822A (zh) | 独脚金内酯(±)‑gr24及4位取代的(±)‑gr24的合成方法 | |
| Shi et al. | Brønsted acid TfOH-mediated reactions of 2-(arylmethylene) cyclopropylcarbinols with acetonitrile | |
| Sun et al. | Diastereoselective Synthesis of 3-Hydroxyindanones via N-Heterocyclic Carbene Catalyzed [4+ 1] Annulation of Phthalaldehyde and 1, 2-Diactivated Michael Acceptors | |
| CN104945231B (zh) | 以2‑卤代环戊酮为原料合成1，4‑二酮化合物的方法 | |
| CN110317170B (zh) | 一种3-菲啶基甲酸丙酯类化合物的绿色合成方法 | |
| CN111018779B (zh) | 一种2-(3-异喹啉基)-丙酸乙酯衍生物及合成方法 | |
| Babudri et al. | A novel stereoselective synthesis of symmetrical (1E, 3E)-1, 4-diarylbuta-1, 3-dienes | |
| CN108129348B (zh) | 叠氮三氟甲氧基化合物及其合成方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20200303 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |