CN113264883A - 一种快速合成菲啶类化合物的方法 - Google Patents
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- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 7
- -1 phenanthridine compound Chemical class 0.000 title description 10
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthrridine Natural products C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 title description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 160
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 105
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims abstract description 82
- 239000002904 solvent Substances 0.000 claims abstract description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 38
- 239000012043 crude product Substances 0.000 claims abstract description 38
- 239000000047 product Substances 0.000 claims abstract description 37
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 35
- 239000012074 organic phase Substances 0.000 claims abstract description 35
- 229910052938 sodium sulfate Inorganic materials 0.000 claims abstract description 35
- 235000011152 sodium sulphate Nutrition 0.000 claims abstract description 35
- 238000000605 extraction Methods 0.000 claims abstract description 34
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- AFMVESZOYKHDBJ-UHFFFAOYSA-N fluoren-9-ol Chemical compound C1=CC=C2C(O)C3=CC=CC=C3C2=C1 AFMVESZOYKHDBJ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000005053 phenanthridines Chemical class 0.000 claims abstract description 9
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- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 68
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical group FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 36
- 238000010898 silica gel chromatography Methods 0.000 claims description 34
- 239000007858 starting material Substances 0.000 claims description 34
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 2
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 2
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- 229910052723 transition metal Inorganic materials 0.000 abstract description 5
- 150000003624 transition metals Chemical class 0.000 abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 abstract description 3
- 125000003118 aryl group Chemical group 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000001257 hydrogen Substances 0.000 abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 3
- 229910052751 metal Inorganic materials 0.000 abstract description 3
- 239000002184 metal Substances 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 2
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 54
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- 229910052757 nitrogen Inorganic materials 0.000 description 34
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- UJPHBDAPVWFPTG-UHFFFAOYSA-N 9-phenylfluoren-9-ol Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(O)C1=CC=CC=C1 UJPHBDAPVWFPTG-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- WKMNILFJGKLWSI-UHFFFAOYSA-N 2-(fluoren-9-ylidenemethyl)pyridine Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1=CC1=CC=CC=N1 WKMNILFJGKLWSI-UHFFFAOYSA-N 0.000 description 1
- JGLAFFHWKBXNNT-KGVSQERTSA-N 9-[(e)-but-2-en-2-yl]carbazole Chemical compound C1=CC=C2N(C(/C)=C/C)C3=CC=CC=C3C2=C1 JGLAFFHWKBXNNT-KGVSQERTSA-N 0.000 description 1
- NLYQLGNCJSGXED-UHFFFAOYSA-N CC1=C2C(=CC=C1)C(C3=CC=CC(=C32)C)O Chemical compound CC1=C2C(=CC=C1)C(C3=CC=CC(=C32)C)O NLYQLGNCJSGXED-UHFFFAOYSA-N 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
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- 150000001875 compounds Chemical class 0.000 description 1
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007154 radical cyclization reaction Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
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- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
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Abstract
本发明公开了一种快速合成菲啶类化合物的方法,是以9‑芴醇1作为起始原料,室温下将9‑芴醇1和叠氮化物2在溶剂中混合均匀,其后缓慢滴加三氟乙酸,滴加完成后将反应体系置于室温下搅拌反应3小时;TLC点板监测原料反应完全后向反应体系中缓慢滴加碳酸氢钠饱和水溶液调节pH值至8,然后加入乙酸乙酯萃取,合并有机相,硫酸钠干燥,旋蒸除去有机溶剂后得到粗产物,分离纯化后得到目标产物3。本反应在室温下即可进行,能耗低,反应过程中不使用过渡金属及金属有机试剂,生产成本低,生产废水对环境的污染较小。本反应可以得到一系列的菲啶类化合物,包含6位为氢、烷基、芳基基团,反应大多数情况下产率大于90%。
Description
技术领域
本发明涉及一种已知化合物的合成方法,具体涉及一种快速合成菲啶类化合物的方法,属于有机合成领域。
背景技术
目前,菲啶类化合物的合成主要集中于两个技术路线。一个是自由基环化策略,其首先在反应中产生自由基,然后通过加成或其他方式产生5位N端或6位C端自由基,最后环化芳构化完成菲啶的合成。它有几个比较大的缺点,其一,不能合成6位为氢取代基团的菲啶,而这类菲啶在生物活性分子中占绝大多数;其二,取代基的拓展受自由基反应活性的影响较大,自由基需要特殊的官能团才能引发。另一个技术路线是过渡金属参与的反应,其主要使用一些芳基卤代物作为起始原料,通过一些串联反应或C-H官能团化构建菲啶类化合物。通常含有复杂官能团的芳基卤代物难以制备,这类反应使用昂贵的过渡金属钯、铑、铱等作为催化剂,生产成本高,反应废料对环境污染大。
发明内容
本发明针对上述现有技术所存在的不足,提供了一种简单高效的快速合成菲啶类化合物的方法。本方法以9-芴醇作为起始原料,不使用过渡金属及金属有机试剂,在室温下以43-99%收率得到菲啶类化合物;其中,6位可以是氢、烷基、芳基基团。本方法可以实现克级规模制备菲啶类化合物。
本发明快速合成菲啶类化合物的方法,是以9-芴醇作为起始原料,室温下将9-芴醇和叠氮化物在溶剂中混合均匀,其后缓慢滴加三氟乙酸,滴加完成后将反应体系置于室温下搅拌反应3小时;TLC点板监测原料反应完全后向反应体系中缓慢滴加碳酸氢钠饱和水溶液调节pH 值至8,然后加入乙酸乙酯萃取,合并有机相,硫酸钠干燥,旋蒸除去有机溶剂后得到粗产物,分离纯化后得到目标产物。
所述叠氮化物包括叠氮化钠、三甲基硅基叠氮等。
所述溶剂为六氟异丙醇。
进一步地,9-芴醇和叠氮化物的摩尔比为1:3;三氟乙酸的添加体积为溶剂体积的1/10。
进一步地,所述分离纯化是通过硅胶柱层析进行分离纯化,洗脱液为PE和EA按体积比95: 5混合构成。
本发明上述反应在氮气气氛中进行。
本发明反应路线如下:
本发明的起始原料9-芴醇简单易得,通过叠氮化物的重排反应合成菲啶类化合物,反应在室温下即可进行,能耗低。反应过程中不使用过渡金属及金属有机试剂,仅仅使用工业化的叠氮化钠或三甲基硅基叠氮,生产成本低,生产废水对环境的污染较小。本发明反应可以得到一系列的菲啶类化合物,包含6位为氢、烷基、芳基基团,反应大多数情况下产率大于90%。
具体实施方式
实施例1:
在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-芴醇(42mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3a(24mg,59%)。
1H NMR(500MHz,Chloroform-d)δ9.06(s,1H),7.96(d,J=8.0Hz,1H),7.86–7.81(m, 1H),7.68–7.63(m,2H),7.63–7.60(m,1H),7.48(d,J=7.5Hz,1H),2.61(s,3H),2.60(s, 3H).13C NMR(126MHz,Chloroform-d)δ153.2,145.8,135.2,135.1,133.0,132.2,129.0,128.4, 127.5,126.7,126.0,125.3,124.2,22.7,22.4.HRMS(ESI)calcd forC15H13N[M+H]+208.1126, found 208.1129.
实施例2:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5,9-三甲基9-芴醇(45mg,0.2 mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3b(20mg,45%)。
1H NMR(500MHz,Chloroform-d)δ8.00(dd,J=7.5,1.5Hz,1H),7.87(dd,J=8.0,1.5Hz, 1H),7.65–7.59(m,2H),7.60–7.56(m,1H),7.40(d,J=7.5Hz,1H),2.96(s,3H),2.60(s,3H), 2.57(s,3H).13C NMR(126MHz,Chloroform-d)δ158.2,144.9,135.3,134.9,132.4,132.2,128.2, 128.0,127.4,126.4,125.2,123.9,122.7,23.1,22.5,22.4.HRMS(ESI)calcd for C16H15N [M+H]+222.1283,found 222.1279.
实施例3:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-正丁基-9-芴醇(53mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3c(23mg,43%)。
1H NMR(400MHz,Chloroform-d)δ8.07–8.00(m,1H),7.91–7.85(m,1H),7.63–7.60(m, 1H),7.60–7.55(m,2H),7.43–7.36(m,1H),3.43–3.14(m,2H),2.59(s,3H),2.57(s,3H),1.97 –1.78(m,2H),1.54(h,J=7.4Hz,2H),1.09–0.91(m,3H).13C NMR(101MHz,Chloroform-d) δ161.7,145.0,135.4,134.9,132.8,132.0,128.1,127.4,127.3,126.2,125.3,123.8,122.6,35.9, 31.6,23.1,22.5,22.4,14.0.HRMS(ESI)calcd for C19H21N[M+H]+264.1752,found 264.1750.
实施例4:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-异丙基-9-芴醇(50mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3d(42mg,85%)。
1H NMR(500MHz,Chloroform-d)δ8.14–8.09(m,1H),7.93(d,J=8.0Hz,1H),7.63–7.60(m,1H),7.60–7.57(m,2H),7.40(d,J=7.5Hz,1H),3.92(p,J=6.8Hz,1H),2.60(s,3H), 2.57(s,3H),1.54(s,3H),1.47(s,3H).13C NMR(126MHz,Chloroform-d)δ165.0,145.0,135.4, 134.8,132.9,131.6,127.9,127.2,126.8,126.1,125.6,123.7,121.8,31.2,22.5,22.3,22.1,21.7. HRMS(ESI)calcd for C18H19N[M+H]+250.1596,found250.1590.
实施例5:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-苯基-9-芴醇(57mg, 0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3e(56mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.01(dd,J=8.0,1.5Hz,1H),7.88–7.83(m,1H),7.76 –7.71(m,2H),7.66–7.61(m,2H),7.57–7.54(m,1H),7.54–7.53(m,1H),7.53–7.51(m,1H), 7.51–7.49(m,1H),7.49–7.46(m,1H),2.65(s,3H),2.64(s,3H).13C NMR(126MHz,Chloroform-d)δ160.7,144.9,139.7,135.3,134.9,133.2,132.4,129.5,128.6,128.5,128.3,127.6, 127.5,126.3,126.1,125.4,123.7,22.51,22.45.HRMS(ESI)calcd forC21H17N[M+H]+284.1438, found 284.1440.
实施例6:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-苯基-9-芴醇(57mg, 0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中滴加一滴三氟乙酸(催化量),其后将此反应体系置于室温下反应三个小时。对反应进行TLC监测,体系中为大量原料剩余和痕量产物(产率小于5%)。
实施例7:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-苯基-9-芴醇(57mg, 0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(23μL,3.0equiv),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至 8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3e(22mg,78%)。
从实施例5-7可以得出结论,三氟乙酸的添加对反应的顺利进行以及产率有重要影响,最佳添加比例为溶剂的1/10。
实施例8:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-苯基-9-芴醇(57mg, 0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和甲苯(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时。对反应进行TLC监测,未发现预期产物。
实施例9:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-苯基-9-芴醇(57mg, 0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和1,2-二氯乙烷(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时。对反应进行TLC监测,未发现预期产物。
从实施例5,8,9可以得出结论,六氟异丙醇作为溶剂对反应的顺利进行至关重要,使用其他溶剂不能得到预期的扩环产物。
实施例10:
同实施例1,在氮气保护下,向Schlenk反应管中加入7-苯基-7-二苯并[c,g]-7-芴醇(72 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3f(71mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.65(d,J=8.5Hz,1H),8.53(d,J=8.5Hz,1H),8.22 (d,J=9.0Hz,1H),8.11(d,J=8.5Hz,1H),8.05(d,J=9.0Hz,1H),8.02–7.95(m,2H),7.91(d, J=9.0Hz,1H),7.82–7.76(m,2H),7.67–7.62(m,1H),7.62–7.58(m,2H),7.58–7.52(m,2H), 7.40–7.31(m,2H).13C NMR(126MHz,Chloroform-d)δ159.7,145.1,139.7,133.8,132.5,132.3, 130.0,129.5,129.2,128.7,128.6,128.5,128.4,128.0,127.89,127.87,127.8,126.7,124.9,124.7, 124.2,120.1.HRMS(ESI)calcd for C27H17N[M+H]+356.1439,found 356.1442.
实施例11:
同实施例1,在氮气保护下,向Schlenk反应管中加入9-苯基-9-芴醇(52mg,0.2mmol, 1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯 (5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3g(51mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.75–8.68(m,1H),8.63(dd,J=8.0,1.5Hz,1H),8.26 (dd,J=8.0,1.5Hz,1H),8.11(dd,J=8.0,1.5Hz,1H),7.86(ddd,J=8.5,7.0,1.5Hz,1H),7.80– 7.76(m,1H),7.76–7.72(m,2H),7.70(ddd,J=8.5,7.0,1.5Hz,1H),7.62(ddd,J=8.0,7.0,1.0 Hz,1H),7.60–7.55(m,2H),7.55–7.49(m,1H).13C NMR(126MHz,Chloroform-d)δ161.2, 143.8,139.8,133.4,130.5,130.3,129.7,128.9,128.8,128.7,128.4,127.1,126.9,125.2,123.7, 122.2,121.9.HRMS(ESI)calcd for C19H13N[M+H]+256.1126,found 256.1129.
实施例12:
同实施例1,在氮气保护下,向Schlenk反应管中加入9-苯基-9-芴醇(1.550g,6mmol, 1.0equiv),叠氮化钠(1.170g,18mmol,3.0equiv)和六氟异丙醇(60.0mL),在室温下向混合物中缓慢滴加三氟乙酸(6.0mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯 (20.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3g(1.450g,95%)。
实施例13:
同实施例1,在氮气保护下,向Schlenk反应管中加入2,4,5,7-四甲基-9-苯基-9-芴醇(63 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3h(62mg,99%)。
1H NMR(500MHz,Chloroform-d)δ7.81(s,1H),7.75–7.70(m,2H),7.62(s,1H),7.58– 7.52(m,2H),7.52–7.48(m,1H),7.45(s,1H),7.29(s,1H),2.61(s,3H),2.59(s,3H),2.55(s,3H), 2.46(s,3H).13C NMR(126MHz,Chloroform-d)δ160.5,144.8,140.0,137.2,135.6,134.8,134.4, 133.9,131.3,130.3,129.5,128.4,128.3,127.4,126.1,125.1,121.7,22.5,22.4,21.3,21.2.HRMS (ESI)calcd for C23H21N[M+Na]+334.1572,found334.1565.
实施例14:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-2,7,9-三苯基-9-芴醇(88 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3i(51mg,59%)。
1H NMR(500MHz,Chloroform-d)δ8.31(d,J=2.0Hz,1H),8.10(d,J=2.0Hz,1H),7.92– 7.89(m,1H),7.87–7.82(m,2H),7.82–7.77(m,2H),7.77–7.75(m,1H),7.66–7.61(m,2H), 7.60–7.55(m,2H),7.56–7.51(m,2H),7.51–7.47(m,2H),7.46–7.44(m,1H),7.42–7.35(m, 2H),2.76(s,3H),2.74(s,3H).13C NMR(126MHz,Chloroform-d)δ161.4,145.4,140.2,140.09, 140.07,139.6,138.9,135.8,135.4,132.5,131.5,129.6,128.94,128.91,128.7,128.5,127.9,127.8, 127.7,127.6,127.3,127.2,124.1,123.5,22.84,22.80.HRMS(ESI)calcd for C33H25N [M+H]+436.2065,found 436.2074.
实施例15:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对甲苯基-9-芴醇(60 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3j(59mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.01(d,J=8.0,1.5Hz,1H),7.89(dd,J=8.0,1.5Hz, 1H),7.67–7.63(m,2H),7.63–7.59(m,2H),7.50(t,J=7.5Hz,1H),7.46(d,J=7.5Hz,1H), 7.36(d,J=7.5Hz,2H),2.64(s,3H),2.63(s,3H),2.47(s,3H).13C NMR(126MHz,Chloroform-d) δ160.7,144.9,138.4,136.7,135.2,134.9,133.2,132.3,129.5,129.0,128.5,127.6,127.5,126.2, 126.1,125.4,123.6,22.5,22.4,21.4.HRMS(ESI)calcd for C22H19N[M+H]+298.1596,found 298.1602.
实施例16:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对甲苯基-9-芴醇(60 mg,0.2mmol,1.0equiv),三甲基硅基(78μL,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3j(59mg,99%)。
实施例17:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对氯苯基-9-芴醇(64 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品。粗品经过硅胶柱层析(PE/EA 95/5)得到纯品3k(62mg,97%)。
1H NMR(500MHz,Chloroform-d)δ7.99(dd,J=8.0,1.5Hz,1H),7.81(dd,J=8.0,1.5Hz, 1H),7.70–7.66(m,2H),7.66–7.64(m,1H),7.64–7.61(m,1H),7.55–7.52(m,2H),7.52– 7.50(m,1H),7.50–7.46(m,1H),2.64(s,3H),2.63(s,3H).13C NMR(126MHz,Chloroform-d)δ 159.4,144.8,138.1,135.5,135.0,134.7,133.2,132.5,131.0,128.9,128.6,127.8,127.2,126.4, 126.1,125.0,123.7,22.5,22.4.HRMS(ESI)calcd forC21H16ClN[M+H]+318.1050,found 318.1049.
实施例18:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对叔丁苯基-9-芴醇(68 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3l(67mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.00(d,J=8.0Hz,1H),7.93(d,J=8.0Hz,1H),7.70– 7.65(m,2H),7.65–7.60(m,2H),7.59–7.54(m,2H),7.51(t,J=7.5Hz,1H),7.46(d,J=7.5Hz, 1H),2.65(s,3H),2.63(s,3H),1.41(s,9H).13C NMR(126MHz,Chloroform-d)δ160.7,151.5, 145.0,136.7,135.2,134.9,133.2,132.3,129.3,128.5,127.6,127.5,126.2,126.1,125.5,125.3, 123.7,34.7,31.4,22.51,22.45.HRMS(ESI)calcd forC25H25N[M+H]+340.2065,found 340.2072.
实施例19:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对甲氧基苯基-9-芴醇 (63mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0 mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品。粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3m(50mg,80%)。
1H NMR(500MHz,Chloroform-d)δ7.98(d,J=8.0Hz,1H),7.90(d,J=8.0Hz,1H),7.72– 7.67(m,2H),7.64–7.59(m,2H),7.51(t,J=7.5Hz,1H),7.45(d,J=7.0Hz,1H),7.10–7.04(m, 2H),3.90(s,3H),2.64(s,3H),2.62(s,3H).13C NMR(126MHz,Chloroform-d)δ160.3,160.0, 144.9,135.3,134.9,133.2,132.3,132.1,131.0,128.4,127.6,127.5,126.2,126.0,125.4,123.6, 113.8,55.4,22.5,22.4.HRMS(ESI)calcd for C22H19ON[M+H]+314.1545,found 314.1550.
实施例20:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对碘苯基-9-芴醇(82 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3n(56mg,69%)。
1H NMR(500MHz,Chloroform-d)δ7.98(d,J=8.0Hz,1H),7.93–7.86(m,2H),7.81(d,J =8.0Hz,1H),7.67–7.61(m,2H),7.52(t,J=7.5Hz,1H),7.50–7.48(m,2H),7.48–7.45(m, 1H),2.64(s,3H),2.63(s,3H).13C NMR(126MHz,Chloroform-d)δ159.5,144.8,139.1,137.5, 135.5,135.0,133.2,132.5,131.4,128.9,127.8,127.1,126.4,126.1,124.9,123.7,94.7,22.52, 22.45.HRMS(ESI)calcd for C21H16IN[M+Na]+432.0225,found432.0233.
实施例21:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对三氟甲基苯基-9- 芴醇(71mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节 pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3o(67mg,96%)。
1H NMR(500MHz,Chloroform-d)δ8.00(dd,J=8.0,1.5Hz,1H),7.86(d,J=8.0Hz,2H), 7.81(d,J=8.0Hz,2H),7.79–7.74(m,1H),7.68–7.63(m,2H),7.53(t,J=7.5Hz,1H),7.51(d, J=7.0Hz,1H),2.66(s,3H),2.64(s,3H).13C NMR(126MHz,Chloroform-d)δ159.1,144.8, 143.3,135.6,135.1,133.2,132.7,130.6(q,J=32.4Hz),130.0,129.1,127.9,127.4,127.1,126.5, 126.2,125.4(q,J=3.8Hz),125.3,124.8,123.8,123.1,22.53,22.46.19F NMR(471MHz, Chloroform-d)δ-62.6.HRMS(ESI)calcd for C22H16F3N[M+H]+352.1313,found 352.1306.
实施例22:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对三氟甲基苯基-9- 芴醇(71mg,0.2mmol,1.0equiv),三甲基硅基(78μL,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3o(63mg,90%)。
实施例23:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对氟苯基-9-芴醇(61 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3p(60mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.01(d,J=8.0Hz,1H),7.84(d,J=8.0Hz,1H),7.79– 7.71(m,2H),7.69–7.64(m,2H),7.55(t,J=7.5Hz,1H),7.50(d,J=7.0Hz,1H),7.29–7.26(m, 1H),7.26–7.22(m,1H),2.67(s,3H),2.66(s,3H).13C NMR(126MHz,Chloroform-d)δ163.1(d, 1JC-F=248.2Hz),159.6,144.8,135.5(4JC-F=3.3Hz),135.4,135.0,133.2,132.5,131.4(3JC-F=8.3 Hz),128.8,127.7,127.3,126.4,126.1,125.1,123.7,115.4(2JC-F=21.7Hz),22.51,22.45.19F NMR(471MHz,Chloroform-d)δ-113.1.HRMS(ESI)calcd for C21H16FN[M+H]+302.1345, found 302.1352.
实施例24:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-对氟苯基-9-芴醇(61 mg,0.2mmol,1.0equiv),三甲基硅基(78μL,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3p(60mg,99%)。
实施例25:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-间甲基苯基-9-芴醇(60 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3q(59mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.01(dd,J=8.0,1.5Hz,1H),7.86(dd,J=8.0,1.5Hz, 1H),7.66–7.61(m,2H),7.55(s,1H),7.53–7.50(m,1H),7.50–7.45(m,2H),7.42(t,J=7.5Hz, 1H),7.33–7.29(m,1H),2.64(s,3H),2.63(s,3H),2.46(s,3H).13C NMR(126MHz,Chloroform-d)δ160.9,144.9,139.6,138.1,135.2,134.9,133.1,132.3,130.1,129.3,128.6,128.1, 127.6,127.5,126.6,126.2,126.1,125.5,123.7,22.50,22.45,21.5.HRMS(ESI)calcd for C22H19N [M+H]+298.1596,found 298.1602.
实施例26:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-邻甲基苯基-9-芴醇(60 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3r(59mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.01(dd,J=8.0,1.5Hz,1H),7.67–7.63(m,1H),7.63 –7.60(m,1H),7.51–7.48(m,1H),7.48–7.45(m,2H),7.42–7.36(m,2H),7.36–7.30(m,2H), 2.66(s,3H),2.65(s,3H),2.12(s,3H).13C NMR(126MHz,Chloroform-d)δ144.9,139.1,135.2, 135.0,132.7,132.4,130.2,128.8,128.4,127.9,127.6,126.4,126.1,125.8,125.0,123.9,22.59, 22.55,19.8.HRMS(ESI)calcd for C22H19N[M+H]+298.1596,found 298.1602.
实施例27:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-邻溴苯基-9-芴醇(73 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3s(66mg,91%)。
1H NMR(500MHz,Chloroform-d)δ8.02(d,J=8.0Hz,1H),7.73(d,J=8.0Hz,1H),7.68– 7.61(m,2H),7.54–7.50(m,2H),7.50–7.47(m,2H),7.46–7.42(m,1H),7.40–7.34(m,1H), 2.66(s,6H).13C NMR(126MHz,Chloroform-d)δ144.8,140.5,135.3,135.1,132.8,132.7,132.6, 129.9,129.2,127.7,127.6,127.3,126.5,126.2,124.9,124.1,22.64,22.57.HRMS(ESI)calcd for C21H16BrN[M+H]+362.0544,found 362.0554
实施例28:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-间二甲基苯基-9-芴醇 (63mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0 mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3t(59mg,95%)。
1H NMR(500MHz,Chloroform-d)δ8.01(dd,J=8.0,1.0Hz,1H),7.86(dd,J=8.0,1.0Hz, 1H),7.65–7.60(m,2H),7.51(t,J=7.5Hz,1H),7.46(d,J=7.0Hz,1H),7.32(s,2H),7.13(s, 1H),2.64(s,3H),2.63(s,3H),2.42(s,6H).13C NMR(126MHz,Chloroform-d)δ161.1,144.9, 139.5,137.8,135.2,134.9,133.1,132.3,130.2,128.5,127.60,127.57,127.2,126.2,126.1,125.6, 123.7,22.5,22.4,21.4.HRMS(ESI)calcd for C23H21N[M+Na]+334.1572,found 334.1565.
实施例29:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-间二甲基苯基-9-芴醇 (63mg,0.2mmol,1.0equiv),三甲基硅基(78μL,0.6mmol,3.0equiv)和六氟异丙醇(2.0 mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3t(62mg,98%)。
实施例30:
同实施例1,在氮气保护下,向Schlenk反应管中加入4,5-二甲基-9-二苯并[b,d]呋喃-2- 基-9-芴醇(75mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3u(68mg,91%)。
1H NMR(500MHz,Chloroform-d)δ8.35(d,J=1.5Hz,1H),8.04(d,J=8.0Hz,1H),7.98 (d,J=7.5Hz,1H),7.91(d,J=8.0Hz,1H),7.83(dd,J=8.0,1.5Hz,1H),7.73(d,J=8.0Hz,1H), 7.68–7.66(m,1H),7.66–7.62(m,2H),7.55–7.52(m,1H),7.52–7.48(m,2H),7.37(td,J=7.5, 1.0Hz,1H),2.67(s,3H),2.66(s,3H).13C NMR(126MHz,Chloroform-d)δ160.5,156.7,156.4, 144.9,135.4,135.0,134.4,133.3,132.4,128.8,128.7,127.74,127.70,127.4,126.4,126.1,125.5, 124.5,124.1,123.7,122.9,122.0,120.9,111.8,111.5,22.54,22.47.HRMS(ESI)calcd for C27H19NO[M+H]+374.1545,found 374.1544.
实施例31:
同实施例1,在氮气保护下,向Schlenk反应管中加入3,6,9-三苯基-9-芴醇(82mg,0.2 mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品3v(57mg,70%)。
1H NMR(400MHz,Chloroform-d)δ8.87(d,J=1.6Hz,1H),8.80(d,J=1.6Hz,1H),8.27 (d,J=8.4Hz,1H),8.14(d,J=8.4Hz,1H),7.96(dd,J=8.4,2.0Hz,1H),7.80(dd,J=8.4,2.0 Hz,1H),7.78–7.76(m,1H),7.76–7.75(m,2H),7.75–7.73(m,2H),7.57–7.54(m,1H),7.54– 7.51(m,2H),7.51–7.49(m,2H),7.49–7.47(m,2H),7.44–7.36(m,2H).13C NMR(101MHz, Chloroform-d)δ160.9,143.4,143.3,141.0,140.5,139.8,139.7,133.8,130.8,129.8,129.5,129.1, 129.0,128.8,128.5,128.4,128.2,127.7,127.6,126.6,124.4,124.0,120.4,120.3.HRMS (ESI)calcd for C31H21N[M+H]+408.1752,found 408.1748.
实施例32:
同实施例1,在氮气保护下,向Schlenk反应管中加入9-(5,5,8,8-四甲基-5,6,7,8-四氢萘 -2-基)-9-芴醇(74mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3w(67mg,91%)。
1H NMR(500MHz,Chloroform-d)δ8.71(d,J=8.0Hz,1H),8.62(d,J=7.5Hz,1H),8.25 (d,J=8.0Hz,1H),8.19(d,J=8.0Hz,1H),7.89–7.83(m,1H),7.78–7.72(m,1H),7.71–7.65 (m,1H),7.65–7.61(m,2H),7.55–7.47(m,2H),1.79–1.74(m,4H),1.37(s,6H),1.35(s, 6H).13C NMR(126MHz,Chloroform-d)δ161.7,145.4,144.6,143.9,136.8,133.5,130.4,130.3, 129.1,128.7,128.1,127.0,126.8,126.7,125.4,123.6,122.1,121.9,35.2,35.1,34.4,34.3,31.89, 31.85.HRMS(ESI)calcd for C27H27N[M+H]+366.2222,found366.2226.
实施例33:
同实施例1,在氮气保护下,向Schlenk反应管中加入9-(1,4(1,4)-二苯甲环环己基-12- 基)-9-芴醇(78mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3x(76mg,99%)。
1H NMR(500MHz,Chloroform-d)δ8.72–8.63(m,2H),8.48–8.42(m,1H),7.92(d,J= 8.5Hz,1H),7.87–7.82(m,1H),7.82–7.77(m,1H),7.77–7.69(m,1H),7.55–7.48(m,1H),7.24(dd,J=8.0,2.0Hz,1H),6.98(d,J=1.5Hz,1H),6.75(dd,J=8.0,2.0Hz,1H),6.70–6.64 (m,2H),6.61(d,J=8.0Hz,2H),3.32–3.20(m,2H),3.15–3.06(m,2H),2.97–2.76(m,4H). 13C NMR(126MHz,Chloroform-d)δ160.4,144.3,139.7,139.52,139.49,139.3,137.0,134.6, 134.0,133.7,133.6,132.9,132.5,132.2,131.8,130.8,130.0,128.6,128.5,127.0,126.7,126.0, 123.5,122.0,121.9,35.44,35.39,35.3,34.5.HRMS(ESI)calcd forC29H23N[M+H]+386.1909, found 386.1908.
实施例34:
同实施例1,在氮气保护下,向Schlenk反应管中加入9-(正丁基-3-烯-1-基)-9-芴醇(47 mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH值至8,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3y(15mg,32%)。
1H NMR(500MHz,Chloroform-d)δ8.72–8.63(m,2H),8.48–8.42(m,1H),7.92(d,J=8.5Hz,1H),7.87–7.82(m,1H),7.82–7.77(m,1H),7.77–7.69(m,1H),7.55–7.48(m,1H),7.24(dd,J=8.0,2.0Hz,1H),6.98(d,J=1.5Hz,1H),6.75(dd,J=8.0,2.0Hz,1H),6.70–6.64 (m,2H),6.61(d,J=8.0Hz,2H),3.32–3.20(m,2H),3.15–3.06(m,2H),2.97–2.76(m,4H). 13C NMR(126MHz,Chloroform-d)δ160.4,144.3,139.7,139.52,139.49,139.3,137.0,134.6, 134.0,133.7,133.6,132.9,132.5,132.2,131.8,130.8,130.0,128.6,128.5,127.0,126.7,126.0, 123.5,122.0,121.9,35.44,35.39,35.3,34.5.HRMS(ESI)calcd forC17H15N[M+H]+234.1283, found 234.1281.
实施例35:
同实施例1,在氮气保护下,向Schlenk反应管中加入9-苯基-9H-环戊[1,2-c:4,3-c']双菲蒽-9-芴醇(92mg,0.2mmol,1.0equiv),叠氮化钠(39mg,0.6mmol,3.0equiv)和六氟异丙醇(2.0mL),在室温下向混合物中缓慢滴加三氟乙酸(0.2mL),滴加完成后将此反应体系置于室温下反应三个小时;TLC监测原料反应完全并向反应体系中滴加饱和碳酸氢钠调节pH至碱性后,加入乙酸乙酯(5.0mL*3)萃取,合并有机相后使用硫酸钠干燥,旋转蒸发除掉溶剂后得到粗品,粗品经过硅胶柱层析(PE/EA 95/5)得到纯品目标产物3z(62mg,67%)。
1H NMR(500MHz,Chloroform-d)δ8.34(d,J=8.0Hz,1H),8.17(d,J=8.5Hz,1H),8.12 (d,J=9.0Hz,1H),7.97–7.91(m,2H),7.91–7.88(m,1H),7.80(d,J=8.5Hz,1H),7.77(d,J= 8.5Hz,1H),7.68–7.64(m,2H),7.64–7.62(m,1H),7.61–7.57(m,2H),7.37(dd,J=7.5,4.5 Hz,2H),7.18(dd,J=8.5,4.5Hz,2H),7.00–6.92(m,2H),6.52–6.41(m,2H).13CNMR(126 MHz,Chloroform-d)δ159.7,144.4,139.7,132.5,131.8,130.7,130.2,130.0,129.9,129.51, 129.45,129.42,128.7,128.5,128.4,127.73,127.71,127.0,126.9,126.8,125.7,125.6,125.3,125.1, 124.6,124.1,123.92,123.85,123.8,118.2.HRMS(ESI)calcd for C35H21N[M+H]+456.1752found 456.1758。
Claims (8)
1.一种快速合成菲啶类化合物的方法,其特征在于:
以9-芴醇1作为起始原料,室温下将9-芴醇1和叠氮化物2在溶剂中混合均匀,其后缓慢滴加三氟乙酸,滴加完成后将反应体系置于室温下搅拌反应3小时;TLC点板监测原料反应完全后向反应体系中缓慢滴加碳酸氢钠饱和水溶液调节pH值至8,然后加入乙酸乙酯萃取,合并有机相,硫酸钠干燥,旋蒸除去有机溶剂后得到粗产物,分离纯化后得到目标产物3。
2.根据权利要求1所述的方法,其特征在于:
所述叠氮化物2包括叠氮化钠、三甲基硅基叠氮。
3.根据权利要求1所述的方法,其特征在于:
所述溶剂为六氟异丙醇。
5.根据权利要求1、2或4所述的方法,其特征在于:
9-芴醇和叠氮化物的摩尔比为1:3。
6.根据权利要求1、3或4所述的方法,其特征在于:
三氟乙酸的添加体积为溶剂体积的1/10。
7.根据权利要求1所述的方法,其特征在于:
所述分离纯化是通过硅胶柱层析进行分离纯化,洗脱液为PE和EA按体积比95:5混合构成。
8.根据权利要求1所述的方法,其特征在于:
所述反应在氮气气氛中进行。
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US3933893A (en) * | 1972-12-21 | 1976-01-20 | Richardson-Merrell Inc. | Derivatives of 9-phenanthrene |
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US3933893A (en) * | 1972-12-21 | 1976-01-20 | Richardson-Merrell Inc. | Derivatives of 9-phenanthrene |
US3953455A (en) * | 1972-12-21 | 1976-04-27 | Richardson-Merrell Inc. | Derivatives of 6(5H)-phenanthridinone and a method for preparation |
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