CN114380735A - 一种合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法 - Google Patents

一种合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法 Download PDF

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CN114380735A
CN114380735A CN202210154496.2A CN202210154496A CN114380735A CN 114380735 A CN114380735 A CN 114380735A CN 202210154496 A CN202210154496 A CN 202210154496A CN 114380735 A CN114380735 A CN 114380735A
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indeno
fluorene
indole
indolyl
copper
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CN114380735B (zh
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刘建明
晁君丽
岳园园
杨焱
叶雅青
郭晓慧
孙春影
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Henan Normal University
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    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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    • 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
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Abstract

本发明公开了一种合成芴和茚并[2,1‑b]吲哚基螺环吲哚的方法，属于有机化学技术领域。在惰性氛围下，以取代2‑苯基1H‑吲哚1为原料，在三氟乙酸铜和过硫酸钾存在下，有机溶剂中低温反应，得到螺环吲哚化合物2。本发明从简单易得试剂出发，经由简便的操作步骤，在温和反应条件下，经过一步反应即可得到螺环吲哚类化合物，避免了传统合成方法原料复杂、催化成本高等弊端，成功合成了不同系列螺环吲哚类化合物。

Description

一种合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法
技术领域
本发明属于有机化学技术领域，具体涉及一种合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法。
背景技术
螺环化合物是多种药物和天然生物碱的重要骨架，如有效的细胞抑制生物碱螺旋菌前列腺素就是这类化合物。螺环化合物因其独特的生物活性在高分子、农药等方面也具有广泛的应用。含吲哚中心的化合物是具有抗炎、抗疟疾、抗抑郁、抗肿瘤或其他多种活性的众多天然产物和药物的子结构。因此人们非常重视对这种化合物的研究，探索有效地构建各种螺环吲哚类化合物的方法仍然是一项艰巨的任务。
现有合成螺环吲哚类化合物方法存在一定缺陷，例如2-(2-甲氧基苯基)乙腈衍生物与各种烷基和芳基锂试剂反应以制备相应的螺环吲哚；4-(2-氟苯基)-1-甲基哌啶-4-腈在格氏试剂的作用下制备2-([1,1'-联苯]-2-基)-1'-甲基螺[吲哚-3,4'-哌啶]衍生物。这些方法都无法避免强碱或格氏试剂使用且格氏试剂制备存在一定的危险性。
因此，开发出操作简便安全合成螺环吲哚类化合物的方法是非常有必要的。
发明内容
为了克服上述所指出的诸多缺陷，进而寻求合成取代螺环吲哚类化合物的简便方法，本发明公开了一种简单、有效、便捷合成螺环吲哚类化合物的方法。从简单易得试剂出发，经由简便的操作步骤，在温和反应条件下，经过一步反应即可得到螺环吲哚类化合物，避免了传统合成方法原料复杂、催化成本高等弊端，成功合成了不同系列螺环吲哚类化合物。
本发明所述一种合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法，包括以下操作：以取代2-苯基1H-吲哚1为原料，在铜盐催化剂和氧化剂存在下，有机溶剂中低温反应，得到螺环吲哚化合物2。反应方程式如下：
Figure BDA0003509843200000011
其中，R1为氢、C1-C4烷基或卤素；R2为氢、C1-C4烷基、C1-C4烷氧基、卤素或杂环取代基。
进一步地，上述取代基更具体而言，R1选自氢、甲基、氟、氯或溴；R2选自氢、甲基、甲氧基、氟、氯、苯基、噻吩、苯并呋喃或苯并噻吩。
进一步地，在上述技术方案中，所述氧化剂选自过硫酸钠、过硫酸钾中的一种。优选氧化剂为过硫酸钾。
进一步地，在上述技术方案中，所述反应温度选自-10℃至25℃；更进一步地，优化温度为0℃。
进一步地，在上述技术方案中，所述反应溶剂选自TFA(三氟乙酸)、DCE(二氯乙烷)中的一种或两种；优选溶剂为DCE/TFA＝1/1混合溶剂。
进一步地，在上述技术方案中，所述催化剂选自醋酸铜、三氟乙酸铜、硫酸铜、溴化铜、三氟甲磺酸铜或乙酰丙酮铜。优选催化剂为三氟乙酸铜。
进一步地，在上述技术方案中，所述吲哚类化合物1、氧化剂与铜盐催化剂摩尔比为1:1-1.2:0.1-0.2。
进一步地，在上述技术方案中，反应优选在氮气氛围下进行。
为了更好的理解本发明，考察了不同反应条件对反应结果的影响。采用3-([1,1'-联苯]-2-基)-6,7-二甲基-2-苯基-1H-吲哚1a为原料，以三氟乙酸铜铜为催化剂、DCE/TFA为溶剂和氮气条件为例，结果如下：在氮气气氛下，将0.3mmol3-([1,1'-联苯]-2-基)-6,7-二甲基-2-苯基-1H-吲哚1、0.36mmol过硫酸钾、20mol％三氟乙酸铜催化剂和2mL溶剂(DCE:TFA＝1:1)依次加入到Schlenk反应管中，经液氮脱气处理后，在低温泵中0℃条件下搅拌反应24h。反应结束后，真空减压浓缩除去TFA，然后用二氯甲烷(3×20mL)和蒸馏水萃取。合并有机相并用无水硫酸钠干燥有机相。柱层析分离得到目标产物2a，收率为61％。改变其它反应条件时，结果如下：
1)将氧化剂更换为过硫酸钠，得到产物2a，收率为23％。
2)将催化剂更换为醋酸铜、硫酸铜、溴化铜、三氟甲磺酸铜和乙酰丙酮铜，所得目标产物2a产率分别为42％，31％，22％，47％和39％。
3)将反应温度升高至25℃，产物2a收率降为23％。
为了进一步理解反应机理，做了如下对比实验，结果如下：
Figure BDA0003509843200000031
根据以上实验结果，推测反应机理如下：
Figure BDA0003509843200000032
发明有益效果
1)本发明使用非贵金属铜为催化剂，避免了传统制备方法中催化成本高的缺点；
2)本发明可制备不同系列螺环吲哚化合物，具有良好的底物适用范围。
具体实施例
通过以下实例对本发明的上述内容做进一步详细说明，但不应该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实现的技术均属于本发明的范围。
实施例1-17
典型操作过程：在氮气气氛下，将0.3mmol化合物1a-1q、0.36mmol过硫酸钾、20mol％三氟乙酸铜和2mL溶剂(DCE:TFA＝1:1)依次加入到Schlen k反应管中，经液氮脱气处理后，在低温泵中0℃条件下搅拌反应24h。反应结束后，真空减压浓缩除去TFA，然后用二氯甲烷(3×20mL)和蒸馏水萃取。合并有机相并用无水硫酸钠干燥有机相。通过柱层析法分离得到目标产物2a-2q。结果如下：
Figure BDA0003509843200000041
Figure BDA0003509843200000051
Figure BDA0003509843200000061
Standaed condition：1(1.0 equiv，0.3mmol)，Cu(TFA)2H2O(20mol％，0.06mmol)，K2S2O8(1.2 equiv，0.36mmol)，Solvent(2mL)，N2，0℃，24h.
化合物2a-2q表征数据如下：
6′，7′-Dimethy1-2′-phenylspiro[fluorene-9，3′-indole](2a)，61％；1H NMR(400MHz，DMSO-d6)δ8.11(d，J＝7.6Hz，2H)，7.44(t，J＝7.6Hz，2H)，7.36(d，J＝7.2Hz，2H)，7.28-7.24(m，1H)，7.15(t，J＝8.0Hz，4H)，6.86(d，J＝7.6Hz，1H)，6.75(d，J＝7.6Hz，2H)，6.25(d，J＝7.6Hz，1H)，2.65(s，3H)，2.29(s，3H)；13C{1H}NMR(101MHz,DMSO-d6)δ175.4,154.3,144.7,141.1,140.0,136.8,132.1,130.7,129.1,128.4(4),128.3(6),127.8,127.3,123.3,121.4,118.4,71.3,19.3,13.8.HRMS,calculated for C28H22N(M+H+):372.1747,found 372.1749.
2,6',7'-Trimethyl-2'-phenylspiro[fluorene-9,3'-indole](2b),66％；1HNMR(400MHz,CDCl3)δ7.88(d,J＝7.6Hz,1H),7.81(d,J＝8.0Hz,1H),7.54(dd,J＝7.2,2.0Hz,2H),7.39(t,J＝7.6Hz,1H),7.26-7.21(m,2H),7.15-7.09(m,3H),6.87(dd,J＝7.6,16.0Hz,2H),6.69(s,1H),6.41(d,J＝7.6Hz,1H),2.79(s,3H),2.38(s,3H),2.22(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ176.8,154.9,145.5,145.2,141.8,140.7,139.1,138.4,137.1,132.9,130.4,129.7,129.1,128.4,128.1,128.0,127.8,124.5,123.9,120.5,120.5,118.9,71.8,21.6,19.8,14.2.HRMS,calculated for C29H24N(M+H+):386.1903,found386.1900.
2-Methoxy-6',7'-dimethyl-2'-phenylspiro[fluorene-9,3'-indole](2c),76％；1H NMR(400MHz,CDCl3)δ7.76(d,J＝8.0Hz,2H),7.49(d,J＝7.2Hz,2H),7.31(td,J＝7.6,1.2Hz,1H),7.20-7.15(m,1H),7.08(t,J＝7.6Hz,2H),7.00(td,J＝7.6,1.2Hz,1H),6.91(dd,J＝8.4,2.4Hz,1H),6.93(d,J＝7.6Hz,1H),6.77(d,J＝7.6Hz,1H),6.37-6.35(m,2H),3.57(s,3H),2.72(s,3H),2.32(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ176.7,160.3,155.0,147.2,145.0,141.7,140.7,137.1,134.6,132.9,130.4,129.7,128.4,128.2,128.0,127.9,127.1,123.8,121.6,119.9,118.9,114.8,108.9,72.0,55.5,19.8,14.2.HRMS,calculated for C29H24NO(M+H+):402.1852,found 402.1853.
6',7'-Dimethyl-2,2'-diphenylspiro[fluorene-9,3'-indole](2d),50％；1HNMR(400MHz,CDCl3)δ7.90(dd,J＝16.0,8.0Hz,2H),7.62(dd,J＝8.0,1.6Hz,1H),7.50(d,J＝7.6Hz,2H),7.40-7.34(m,3H),7.26(t,J＝7.6Hz,2H),7.21-7.14(m,2H),7.11-7.06(m,4H),6.84-6.81(m,2H),6.38(d,J＝7.6Hz,1H),2.73(s,3H),2.31(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ176.6,155.1,146.2,145.8,141.4,141.3,140.9,140.6,140.4,137.2,132.9,130.5,129.8,128.7,128.4,128.3,128.3,128.0,127.9,127.4,127.3,127.2,124.0,122.5,121.1,120.9,118.9,72.1,19.8,14.2.HRMS,calculated for C34H26N(M+H+):448.2060,found 448.2053.
2-Chloro-6',7'-dimethyl-2'-phenylspiro[fluorene-9,3'-indole](2e),31％；1H NMR(400MHz,CDCl3)δ7.87(d,J＝7.6Hz,1H),7.81(d,J＝8.0Hz,1H),7.46(d,J＝7.6Hz,2H),7.43-7.35(m,2H),7.23(t,J＝7.6Hz,1H),7.17-7.11(m,3H),6.88-6.83(m,3H),6.36(d,J＝7.6Hz,1H),2.74(s,3H),2.36(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ175.8,155.0,147.2,145.4,140.6,140.3,139.7,137.5,133.9,132.7,130.6,130.1,128.7,128.6,128.5,128.4,128.0,128.0,124.3,124.1,121.7,120.9,118.8,71.7,19.8,14.2.HRMS,calculated for C28H21ClN(M+H+):406.1357,found 406.1358.
2-Fluoro-6',7'-dimethyl-2'-phenylspiro[fluorene-9,3'-indole](2f),35％；1H NMR(400MHz,CDCl3)δ7.86-7.83(m,2H),7.48(d,J＝7.2Hz,2H),7.40(t,J＝7.6Hz,1H),7.26–7.21(m,1H),7.15-7.07(m,4H),6.87(dd,J＝10.4,7.6Hz,2H),6.57(dd,J＝8.4,2.4Hz,1H),6.37(d,J＝7.6Hz,1H),2.74(s,3H),2.36(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ176.0,163.0(d,J＝248.5Hz),154.9,147.7,147.6,145.4(d,J＝2.0Hz),140.8,139.9,137.8,137.7,137.5,132.7,130.6,130.0,128.5,128.4,128.1(d,J＝6.1Hz),124.0,121.9(d,J＝8.1Hz),120.5,118.8,115.5(d,J＝23.2Hz),111.5(d,J＝23.2Hz),71.9,19.8,14.2；19F NMR(376MHz,CDCl3)δ-112.81ppm.HRMS,calculated for C28H21FN(M+H+):390.1653,found 390.1658.
6',7'-Dimethyl-2'-phenylspiro[indeno[2,1-b]benzofuran-6,3'-indole](2g),48％；1H NMR(400MHz,CDCl3)δ8.14(dd,J＝6.8,2.0Hz,1H),8.00(dd,J＝7.6,1.6Hz,1H),7.92(dd,J＝7.2,2.0Hz,1H),7.53(dd,J＝7.2,2.0Hz,1H),7.48-7.33(m,5H),7.10-7.02(m,4H),6.83(dd,J＝8.0,2.4Hz,2H),2.71(s,3H),2.38(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ177.2,158.7,156.2,142.3,140.5,138.9,137.5,130.3,128.7,128.7,128.0,127.8,127.5,127.3,127.0,126.3,125.7,124.8,124.3,124.2,122.0,121.9,112.7,111.7,68.2,19.8,14.2.HRMS,calculated for C30H22NO(M+H+):412.1696,found412.1692.
6',7'-Dimethyl-2'-phenylspiro[fluoreno[4,3-b]benzofuran-7,3'-indole](2h),70％；1H NMR(400MHz,CDCl3)δ8.47(d,J＝7.6Hz,1H),7.95(d,J＝7.6Hz,1H),7.76(dd,J＝16.0,8.0Hz,2H),7.56-7.52(m,2H),7.39(t,J＝7.2Hz,1H),7.24-7.19(m,2H),7.11(t,J＝7.6Hz,2H),6.96(d,J＝7.6Hz,1H),6.89(dd,J＝7.6,4.0Hz,2H),6.42(d,J＝7.6Hz,1H),2.81(s,3H),2.38(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ176.3,156.9,155.1,151.0,145.4,145.0,140.2,139.3,137.3,132.9,130.5,129.9,128.6,128.4,128.3,128.0,127.4,126.0,125.0,124.3,124.0,123.8,123.2,120.8,120.3,118.9,118.4,112.1,72.7,19.8,14.2.HRMS,calculated for C34H24NO(M+H+):462.1852,found462.1853.
6',7'-Dimethyl-2'-phenylspiro[indeno[2,1-b]thiophene-8,3'-indole](2i),30％；1H NMR(400MHz,CDCl3)δ7.60(d,J＝7.6Hz,1H),7.51(d,J＝7.2Hz,2H),7.32(t,J＝7.2Hz,1H),7.26-7.22(m,2H),7.15(t,J＝7.6Hz,2H),7.01(t,J＝8.0Hz,1H),6.88(d,J＝7.6Hz,1H),6.77(d,J＝7.6Hz,1H),6.57(d,J＝4.8Hz,1H),6.43(d,J＝7.6Hz,1H),2.72(s,3H),2.35(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ175.4,155.1,148.9,148.2,144.0,138.5,137.9,137.4,133.1,130.6,129.9,128.9,128.5,128.3,127.9,127.8,126.5,123.8,121.5,119.8,118.7,69.3,19.8,14.1.HRMS,calculated for C26H17NS(M+H+):378.1311,found 378.1309.
6',7'-Dimethyl-2'-phenylspiro[benzo[b]indeno[1,2-d]thiophene-6,3'-indole](2j),63％；1H NMR(400MHz,CDCl3)δ8.21(d,J＝8.0Hz,1H),7.89(d,J＝7.6Hz,1H),7.70(d,J＝8.0Hz,1H),7.53(d,J＝7.6Hz,2H),7.46(t,J＝7.6Hz,1H),7.34-7.26(m,2H),7.13(t,J＝7.2Hz,1H),7.04(t,J＝7.6Hz,2H),6.97(t,J＝7.2Hz,1H),6.79(dd,J＝13.2,7.6Hz,2H),6.37(d,J＝7.6Hz,1H),2.66(s,3H),2.27(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ174.8,155.0,149.0,148.5,145.8,141.6,139.1,138.3,137.8,132.9,132.9,130.7,130.1,128.6,128.2,128.1,127.8,126.1,125.1,124.6,124.2,123.4,122.3,120.0,118.8,70.1,19.8,14.2.HRMS,calculated for C30H22NS(M+H+):428.1467,found428.1466.
6',7'-Dimethyl-2'-phenylspiro[benzo[b]fluoreno[3,4-d]thiophene-7,3'-indole](2k),70％；1H NMR(400MHz,CDCl3)δ8.16(t,J＝8.0Hz,2H),8.01(d,J＝7.2Hz,1H),7.97(d,J＝8.0Hz,1H),7.57-7.47(m,5H),7.24-7.17(m,2H),7.08(t,J＝7.6Hz,2H),7.00-6.95(m,2H),6.86(d,J＝7.6Hz,1H),6.37(d,J＝7.6Hz,1H),2.79(s,3H),2.37(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ176.3,155.1,145.9,144.4,140.9,140.0,139.7,137.4,136.7,135.9,135.2,132.9,132.8,130.6,130.0,128.5,128.5,128.3,128.0,128.0,127.1,125.0,123.9,123.2,122.9,121.9,121.4,120.1,118.9,72.5,19.8,14.3.HRMS,calculated for C34H24NS(M+H+):478.1624,found 478.1623.
4-Methoxy-6',7'-dimethyl-2'-phenylspiro[fluorene-9,3'-indole](2l),30％；1H NMR(400MHz,CDCl3)δ8.26(d,J＝7.6Hz,1H),7.51(d,J＝7.6Hz,2H),7.39(t,J＝7.6Hz,1H),7.21(t,J＝7.2Hz,1H),7.14-7.07(m,4H),6.91(d,J＝8.4Hz,1H),6.86-6.81(m,2H),6.47(d,J＝7.6Hz,1H),6.37(d,J＝8.4Hz,1H),4.09(s,3H),2.75(s,3H),2.35(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ176.6,156.3,155.0,147.1,144.6,141.1,140.6,137.1,133.0,130.4,129.7,129.6,129.3,128.4,128.2,128.0,127.9,127.4,124.5,123.3,118.8,116.1,110.3,72.2,55.6,19.8,14.2.HRMS,calculated for C28H24NO(M+H+):402.1852,found 402.1851.
4-Fluoro-6',7'-dimethyl-2'-phenylspiro[fluorene-9,3'-indole](2m),25％；1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.0Hz,1H),7.47(dd,J＝8.0,0.8Hz,2H),7.42(td,J＝7.6,1.2Hz,1H),7.25-7.21(m,1H),7.18-7.07(m,5H),6.86(t,J＝6.8Hz,2H),6.66-6.42(m,1H),6.37(d,J＝7.6Hz,1H),2.74(s,3H),2.35(s,3H)；13C{1H}NMR(101MHz,CDCl3)δ176.0,158.6(d,J＝252.5Hz),154.9,148.1,148.0,144.8,140.0,138.8(d,J＝3.0Hz),137.5,132.7,130.7,130.0,129.6(d,J＝7.1Hz),129.0,128.8,128.6,128.5(3),128.4(8),128.0(3),128.0(0),124.3(d,J＝6.1Hz),123.8,119.7(d,J＝4.0Hz),118.8,115.4(d,J＝20.2Hz),72.3,19.8,14.2；19F NMR(376MHz,CDCl3)δ-118.77.HRMS,calculated for C28H21FN(M+H+):390.1653,found 390.1654.
7'-Chloro-6'-fluoro-2'-phenylspiro[fluorene-9,3'-indole](2n),77％；1HNMR(400MHz,CDCl3)δ7.91(d,J＝8.4Hz,2H),7.49(dd,J＝8.0,1.2Hz,2H),7.43(td,J＝7.6,0.8Hz,2H),7.26-7.22(m,1H),7.17-7.09(m,4H),6.86-6.80(m,3H),6.66-6.62(m,1H)；13C{1H}NMR(101MHz,CDCl3)δ181.0,158.8(d,J＝247.5Hz),154.4,144.0,141.7,139.8(d,J＝3.0Hz),131.9,131.6,128.8,128.6,128.5,123.9,121.1,120.3(d,J＝9.1Hz),114.1(d,J＝23.2Hz),113.8(d,J＝20.2Hz),72.4；19F NMR(376MHz,CDCl3)δ-117.53ppm.HRMS,calculated for C26H16ClFN(M+H+):396.0950,found 396.0949.
6'-Bromo-2'-phenylspiro[fluorene-9,3'-indole](2o),78％；1H NMR(400MHz,CDCl3)δ8.00(d,J＝2.0Hz,1H),7.93(d,J＝8.0Hz,2H),7.47-7.41(m,4H),7.24(t,J＝8.0Hz,1H),7.20-7.10(m,5H),6.84(d,J＝8.0Hz,2H),6.50(d,J＝8.0Hz,1H)；13C{1H}NMR(101MHz,CDCl3)δ179.7,157.5,144.2,142.2,141.8,132.0,131.2,129.4,128.7,128.5,128.2,124.3,123.9,123.3,121.9,121.1,71.4.HRMS,calculated for C26H17BrN(M+H+):422.0539,found 422.0537.
6'-Methyl-2'-phenylspiro[fluorene-9,3'-indole](2p),35％；1H NMR(400MHz,DMSO-d6)δ8.12(d,J＝7.6Hz,2H),7.64(s,1H),7.46(t,J＝7.6Hz,2H),7.34(d,J＝7.2Hz,2H),7.27(t,J＝6.8Hz,2H),7.19-7.14(m,4H),6.90(d,J＝7.6Hz,1H),6.74(d,J＝7.6Hz,2H),6.43(d,J＝7.2Hz,1H),2.38(s,3H)；13C{1H}NMR(101MHz,DMSO-d6)δ176.9,155.8,144.4,141.2,139.8,138.1,131.9,130.9,128.5,128.5,128.4,127.3,123.2,121.5,121.2,70.6,21.1.HRMS,calculated for C27H20N(M+H+):358.1590,found358.1589.
2'-Phenylspiro[benzo[b]indeno[1,2-d]thiophene-6,3'-indole](2q),83％；1H NMR(400MHz,CDCl3)δ8.32(d,J＝8.0Hz,1H),8.01(d,J＝7.6Hz,1H),7.86(d,J＝7.6Hz,1H),7.80(d,J＝8.0Hz,1H),7.61-7.54(m,3H),7.46-7.36(m,3H),7.24(t,J＝7.2Hz,1H),7.16-7.06(m,4H),6.85(d,J＝7.6Hz,1H),6.73(d,J＝7.2Hz,1H)；13C{1H}NMR(101MHz,CDCl3)δ176.4,156.0,148.4,147.8,145.8,142.0,141.1,139.2,132.8,132.4,131.1,129.0,128.6,128.4,127.9,126.9,126.2,125.2,124.7,124.2,123.4,122.4,122.0,121.2,120.1,69.7.HRMS,calculated for C28H18NS(M+H+):400.1154,found 400.1153.
以上实施例描述了本发明的基本原理、主要特征及优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明原理的范围下，本发明还会有各种变化和改进，这些变化和改进均落入本发明保护的范围内。

Claims (7)

1.一种合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法，其特征在于，包括以下操作：以取代2-苯基1H-吲哚1为原料，在铜盐催化剂和氧化剂存在下，有机溶剂中低温反应，得到螺环吲哚化合物2；反应方程式如下：
Figure FDA0003509843190000011
其中，R1为氢、C1-C4烷基或卤素；R2为氢、C1-C4烷基、C1-C4烷氧基、卤素或杂环取代基。
2.根据权利要求1所述合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法，其特征在于：所述氧化剂选自过硫酸钾或过硫酸钠。
3.根据权利要求1所述合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法，其特征在于：所述铜盐催化剂选自醋酸铜、三氟乙酸铜、硫酸铜、溴化铜、三氟甲磺酸铜或乙酰丙酮铜。
4.根据权利要求1所述合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法，其特征在于：所述有机溶剂选自DCE/TFA混合溶剂。
5.根据权利要求1所述合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法，其特征在于：所述吲哚类化合物1、氧化剂与铜盐催化剂摩尔比为1:1-1.2:0.1-0.2。
6.根据权利要求1所述合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法，其特征在于：所述反应温度为-10℃至25℃。
7.根据权利要求1所述合成芴和茚并[2,1-b]吲哚基螺环吲哚的方法，其特征在于：反应在氮气氛围下进行。
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