CN103936649B - 3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物及其制备方法 - Google Patents

3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物及其制备方法 Download PDF

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CN103936649B
CN103936649B CN201410122088.4A CN201410122088A CN103936649B CN 103936649 B CN103936649 B CN 103936649B CN 201410122088 A CN201410122088 A CN 201410122088A CN 103936649 B CN103936649 B CN 103936649B
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acrylate
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刘雄利
袁伟成
黄璇
周英
俸婷婷
林冰
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Juancheng Tiantuo Biotechnology Co ltd
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Guizhou University
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Abstract

本发明公开了一种3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物，本发明以不同取代的3-(2-丙烯酸酯)-3-OBoc氧化吲哚和硫醇类化合物，经有机碱直接催化加成消除反应，合成了3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物，该类骨架包含潜在的生物活性含硫基团和丙烯酸酯类基团，可以为生物活性筛选提供化合物源，对药物的筛选和制药行业具有重要的应用价值。本发明操作简单易行，原料合成便宜易得，可以在各种有机溶剂中进行，也具有较好的空气稳定性，适用性广，对于各种取代基都有很好的兼容性。

Description

3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物及其制备方法
技术领域
本发明涉及化学技术领域，尤其是一种3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物及其制备方法。
背景技术
把具有生物活性基团拼接到一个分子骨架中在有机化学和医药化学中是极其重要的研究领域。（1）氧化吲哚是一类重要的杂环化合物，由于其在农药及医药等各方面的应用，引起来了人们的普遍关注，3-季碳氧化吲哚是其中很重要的一种，很多天然产物中的3-季碳氧化吲哚都具有很好的生物活性。其中，3-季碳硫取代氧化吲哚也存在于生物活性分子和药物分子中。例如，化合物spirobrassinin和methoxyspirobrassinin具有抗肿瘤、抗菌和产卵兴奋剂等生物活性。（2）含硫化合物普遍存在天然产物和药物分子中，在植物中的生物代谢中也包含许多的含硫化合物。如:青霉素、磺胺药、头孢、VB1等。这些化合物在解除病痛、挽救生命中起着重大作用。（3）丙烯酸酯基团也存在于一些活性分子中，例如，甲氧基丙烯酸酯类杀菌剂是一种仿生杀菌剂，是继苯并咪唑和三唑类之后的一个里程碑式的农药杀菌剂；作为化学中间体原料的甲基丙烯酸月桂酯和甲基丙烯酸异冰片酸酯也包含丙烯酸酯基团。鉴于3,3'-双取代氧化吲哚骨架化合物具有潜在的生物活性，硫代基团和丙烯酸酯类基团属于潜在的生物活性官能团。因此，把硫代基团和丙烯酸酯类基团拼接到氧化吲哚骨架，合成一系列新的潜在多活性官能团的氧化吲哚衍生物，可以为生物活性筛选提供化合物源，对药物的筛选和制药行业具有重要的应用价值。
发明内容
本发明的目的是：提供一种3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物及其制备方法，它是一类重要的医药中间体类似物和药物分子类似物，对药物筛选和制药行业具有重要的应用价值，且其合成方法非常经济简便。
本发明是这样实现的：3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物，该化合物具有如下通式（Ⅰ）的结构：
式（Ⅰ）中，R1为烷基、不同取代的芳基或不同取代的酯基；R2为不同取代的酯基，R3为烷基、不同取代的芳基或不同取代的酯基，R4为为氢、卤素或烷基。
所述的3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物，其特征在于：所述的杂芳环为含N、O或S中的一种或几种的五到十元环杂芳环基。
3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物的制备方法，将3-(2-丙烯酸酯)-3-OBoc氧化吲哚化合物与烷基硫醇在碱性催化剂条件下，按摩尔比为3:4的比例在有机溶剂中进行加成消除反应，获得3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物。
所述的有机碱为DABCO或β-ICD(β-6’-羟基异辛克宁3)及其衍生的有机碱，碱性催化剂的加入量为氧化吲哚摩尔量的1-100%。
所述的有机溶剂为乙腈、甲醇、乙醇、丙醇、异丙醇、乙醚、四氢呋喃、苯、甲苯、二甲苯、三甲苯、二氧六环、乙二醇二甲醚、异丙醚、氯仿、二氯甲烷或硝基苯。
3-(2-丙烯酸酯)-3-OBoc氧化吲哚化合物和烷基硫醇反应温度为25-100℃，反应时间为0.1-10小时。
其中，R1，R2，R3，R4如上所述。Cat.为碱性有机催化剂。
通过采用上述技术方案，以不同取代的3-(2-丙烯酸酯)-3-OBoc氧化吲哚与硫醇类化合物，经有机碱直接催化加成消除反应，合成了3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物，该类骨架包含潜在的生物活性含硫基团和丙烯酸酯类基团，可以为生物活性筛选提供化合物源，对药物的筛选和制药行业具有重要的应用价值。本发明操作简单易行，原料合成便宜易得，可以在各种有机溶剂中进行，也具有较好的空气稳定性，适用性广，对于各种取代基都有很好的兼容性。
附图说明
附图1为本发明的实施例的化合物1-24的化学结构；
附图1中，time表示反应时间，yield表示反应产率；
附图2及附图3为本发明的实施例的化合物1的核磁谱图数据；
附图4及附图5为本发明的实施例的化合物2的核磁谱图数据；
附图6及附图7为本发明的实施例的化合物3的核磁谱图数据。
具体实施方式
本发明的实施例1：3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物的制备，在圆底烧瓶中，先加入5毫升有机溶剂二氯甲烷，再依次加入3-(2-丙烯酸甲酯)-3-OBoc-N-苯基氧化吲哚0.3mmol（122.7mg），苄氧羰基亚甲基硫醇0.4mmol（72.8mg），DABCO3.4mg（10mmol%），室温搅拌反应，TLC检测反应完全后，反应液直接硅胶柱层析（300-400目）分离（石油醚：乙酸乙酯=10：1），得到淡黄色油状物。即化合物1。核磁共振和高分辨质谱测试等结果如下：核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.63(d,J=15.9Hz,1H),3.65(s,3H),3.85(d,J=15.9Hz,1H),5.12(s,2H),6.83-6.85(m,3H),7.03-7.10(m,2H),7.22-7.27(m,1H),7.34(s,5H),7.41-7.45(m,1H),7.54(d,J=4.5Hz,4H);13CNMR(CDCl3,75MHz)δ31.5,52.3,55.4,67.2,109.8,122.9,123.5,126.6,126.7,127.8,128.1,128.2,128.3,128.4,129.5,131.2,134.4,135.2,136.1,143.4,164.8,169.2,174.2;IR(KBr)ν1711,1601,1490,1368,1286,1143,767,697cm-1.HRMS(ESI)Calcd.forC27H23NNaO5S[M+Na]+:496.1189;Found:496.1188.
化合物2～24的制备方法同化合物1，投料比与化合物1相同，可得到化合物2～24，反应产率和反应时间见图1，但需强调的是本发明的化合物不限于图1所表示的内容。
本实施例制备化合物2:淡黄色油状物，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ1.65(s,9H),3.55(d,J=15.9Hz,1H),3.61(s,3H),3.70(d,J=15.9Hz,1H),5.13(s,2H),6.78(d,J=8.4Hz,2H),6.98-7.01(m,1H),7.07-7.12(m,1H),7.34(s,6H),7.87(d,J=8.1Hz,1H);13CNMR(CDCl3,75MHz)δ28.1,32.1,52.4,56.1,67.3,84.4,115.6,123.1,124.4,126.8,128.3,128.4,128.5,129.9,131.5,135.2,135.8,139.4,149.2,164.7,168.8,172.1;IR(KBr)ν1797,1723,1290,1145,1097,755cm-1.HRMS(ESI)Calcd.forC26H27NNaO7S[M+Na]+:520.1400;Found:520.1409。
采用本实施例制备化合物3:淡黄色油状物，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ1.10(t,J=7.2Hz,3H),3.25(s,3H),3.55(d,J=15.9Hz,1H),3.77(d,J=15.9Hz,1H),3.96-4.04(m,2H),5.12(s,2H),6.76(d,J=13.8Hz,2H),6.86(d,J=7.8Hz,1H),6.97-7.01(m,2H),7.28-7.35(m,6H);13CNMR(CDCl3,75MHz)δ13.8,26.5,31.4,55.3,61.1,67.2,108.4,122.4,123.2,128.2,128.3,128.4,128.5,129.6,131.1,135.3,136.1,143.3,164.3,169.2,174.9;IR(KBr)ν1707,1601,1490,1151,1086,750cm-1.HRMS(ESI)Calcd.forC23H23NNaO5S[M+Na]+:448.1189;Found:448.1189.
采用本实施例制备化合物4:白色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ0.83(t,J=7.5Hz,3H),1.14-1.19(m,2H),1.41-1.68(m,2H),3.25(s,3H),3.55(d,J=15.9Hz,1H),3.77(d,J=15.9Hz,1H),3.92-3.99(m,2H),5.12(s,2H),6.76(d,J=14.5Hz,2H),6.86(d,J=7.8Hz,1H),6.96-7.03(m,2H),7.28-7.35(m,6H);13CNMR(CDCl3,75MHz)δ13.6,18.9,26.5,30.3,31.4,55.3,65.1,67.2,108.5,122.5,123.2,128.1,128.3,128.4,128.5,129.6,131.3,135.3,136.0,143.3,164.4,169.2,174.8;IR(KBr)ν1711,1605,1499,1090,759,697cm-1.HRMS(ESI)Calcd.forC25H27NNaO5S[M+Na]+:476.1502;Found:476.1520.
采用本实施例制备化合物5:黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.24(s,3H),3.54(d,J=15.9Hz,1H),3.61(s,3H),3.75(d,J=15.9Hz,1H),5.12(s,2H),6.76-6.81(m,4H),6.97-7.04(m,1H),7.31-7.34(m,5H);13CNMR(CDCl3,75MHz)δ26.7,31.3,52.3,55.4,67.2,109.1(d,J CF =8.0Hz),111.3(d,J CF =25.3Hz),115.9(d,J CF =23.2Hz),128.2,128.3,128.5,129.5(d,J CF =8.4Hz),131.5,135.2,135.6,139.3,158.8(d,J CF =239.9Hz),164.7,168.9,174.6;IR(KBr)ν1724,1605,1490,1261,1163,1135,808,562cm-1.HRMS(ESI)Calcd.forC22H20FNNaO5S[M+Na]+:452.0938;Found:452.0927.
采用本实施例制备化合物6:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.24(s,3H),3.54(d,J=15.9Hz,1H),3.61(s,3H),3.75(d,J=15.9Hz,1H),5.12(s,2H),6.77-6.80(m,3H),6.99(d,J=2.1Hz,1H),7.27-7.35(m,6H);13CNMR(CDCl3,75MHz)δ26.7,31.2,52.3,55.1,67.2,109.5,123.6,127.6,128.2,128.3,128.5,129.5,129.6,131.6,135.1,135.4,141.9,164.6,168.9,174.4;IR(KBr)ν1719,1482,1143,1098,975cm-1.HRMS(ESI)Calcd.forC22H20ClNNaO5S[M+Na]+:468.0643;Found:468.0634.
采用本实施例制备化合物7:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.23(s,3H),3.53(d,J=15.9Hz,1H),3.62(s,3H),3.74(d,J=15.9Hz,1H),5.12(s,2H),6.73-6.78(m,3H),7.11(d,J=2.1Hz,1H),7.32-7.37(m,5H),7.41-7.44(m,1H);13CNMR(CDCl3,75MHz)δ26.7,31.3,52.4,55.0,67.3,110.0,114.8,126.4,128.3,128.4,128.5,130.0,131.7,132.5,135.2,135.5,142.4,164.7,168.9,174.4;IR(KBr)ν1718,1601,1490,1323,1143,1090,983,812,742,538cm-1.HRMS(ESI)Calcd.forC22H20BrNNaO5S[M+Na]+:512.0138;Found:512.0139.
采用本实施例制备化合物8:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ1.27(t,J=7.2Hz,3H),3.32(s,3H),3.51(d,J=15.9Hz,1H),3.62(s,3H),3.72(d,J=15.9Hz,1H),4.12-4.19(m,2H),6.82(s,2H),6.70(d,J=7.8Hz,1H),7.01-7.05(m,2H),7.29-7.36(m,1H);13CNMR(CDCl3,75MHz)δ14.0,26.6,31.3,52.2,55.2,61.5,108.5,122.4,123.2,128.0,129.6,131.1,136.0,143.3,164.8,169.2,174.9;IR(KBr)ν1728,1724,1613,1490,1311,1180,750cm-1.HRMS(ESI)Calcd.forC17H19NNaO5S[M+Na]+:372.0876;Found:372.0886.
采用本实施例制备化合物9:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.30(s,3H),3.49(d,J=15.9Hz,1H),3.60(s,3H),3.68(s,3H),3.71(d,J=15.9Hz,1H),6.78(d,J=4.8Hz,2H),6.88(d,J=7.8Hz,1H),6.98-7.01(m,2H),7.29-7.33(m,1H);13CNMR(CDCl3,75MHz)δ26.6,31.1,52.2,52.5,55.3,108.6,122.5,123.2,128.0,129.7,131.1,136.0,143.4,164.8,169.8,174.9;IR(KBr)ν1719,1601,1486,1151,1086,746cm-1.HRMS(ESI)Calcd.forC16H17NNaO5S[M+Na]+:358.0720;Found:358.0726.
采用本实施例制备化合物10:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.31(s,3H),3.62(s,3H),3.79(d,J=12.0Hz,1H),4.07(d,J=12.0Hz,1H),6.81(d,J=6.6Hz,2H),6.87(d,J=7.8Hz,1H),6.99-7.01(m,2H),7.22-7.33(m,6H);13CNMR(CDCl3,75MHz)δ26.6,33.4,52.2,56.6,108.4,122.4,123.0,127.2,128.5,128.6,129.2,129.3,130.9,136.2,143.3,165.0,175.2;IR(KBr)ν1724,1605,1490,1339,1315,1143,1086,763,701cm-1.HRMS(ESI)Calcd.forC20H19NNaO3S[M+Na]+:376.0978;Found:376.0982
采用本实施例制备化合物11:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ1.12(t,J=7.2Hz,3H),3.30(s,3H),3.79(d,J=12.0Hz,1H),3.99-4.08(m,3H),6.77(s,1H),6.86(d,J=8.1Hz,2H),6.99-7.01(m,2H),7.23-7.30(m,6H);13CNMR(CDCl3,75MHz)δ13.7,26.5,33.4,56.6,61.1,108.2,122.4,122.9,127.2,128.5,128.7,129.2,129.3,130.9,136.1,136.3,143.2,164.4,175.1;IR(KBr)ν1711,1605,1486,1339,1143,1090,750cm-1.HRMS(ESI)Calcd.forC21H21NNaO3S[M+Na]+:390.1134;Found:390.1145.
采用本实施例制备化合物12:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ0.85(t,J=7.2Hz,3H),1.16-1.24(m,2H),1.44-1.70(m,2H),3.30(s,3H),3.79(d,J=12.0Hz,1H),3.95-4.01(m,2H),4.06(d,J=12.0Hz,1H),6.77(s,1H),6.86(d,J=7.5Hz,2H),7.00(d,J=6.0Hz,2H),7.23-7.32(m,6H);13CNMR(CDCl3,75MHz)δ13.6,18.9,26.6,30.3,33.5,56.6,65.1,108.3,122.4,123.0,127.2,128.5,128.7,129.2,129.3,131.1,136.2,136.3,143.3,164.6,175.1;IR(KBr)ν1707,1609,1490,1384,1163,754cm-1.HRMS(ESI)Calcd.forC23H25NNaO3S[M+Na]+:418.1447;Found:418.1458.
采用本实施例制备化合物13:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.29(s,3H),3.64(s,3H),3.79(d,J=12.0Hz,1H),4.05(d,J=12.0Hz,1H),6.75-6.83(m,4H),6.96-7.02(m,1H),7.22-7.28(m,5H);13CNMR(CDCl3,75MHz)δ26.8,33.4,52.3,56.8,108.9(d,J CF =8.0Hz),111.2(d,J CF =25.2Hz),115.6(d,J CF =23.3Hz),127.4,128.6,129.2,130.2(d,J CF =8.2Hz),131.4,135.8,135.9,139.3,158.9(d,J CF =239.6Hz),164.9,174.9;IR(KBr)ν1703,1493,1323,1172,1135,963,812,693cm-1.HRMS(ESI)Calcd.forC20H18FNNaO3S[M+Na]+:394.0884;Found:394.0881.
采用本实施例制备化合物14:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.29(s,3H),3.64(s,3H),3.79(d,J=12.0Hz,1H),4.05(d,J=12.0Hz,1H),6.77-6.83(m,3H),6.97(d,J=2.1Hz,1H),7.22-7.30(m,6H);13CNMR(CDCl3,75MHz)δ26.7,33.4,52.4,56.5,109.3,123.5,127.4,127.6,128.6,129.2,129.3,130.2,131.5,135.7,135.8,141.9,164.9,174.7;IR(KBr)ν1715,1486,1315,1159,1094,816,679,542cm-1.HRMS(ESI)Calcd.forC20H18ClNNaO3S[M+Na]+:410.0588;Found:410.0579.
采用本实施例制备化合物15:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.28(s,3H),3.64(s,3H),3.79(d,J=12.0Hz,1H),4.05(d,J=12.0Hz,1H),6.74(d,J=8.4Hz,1H),6.79(s,1H),6.83(s,1H),7.10(d,J=2.1Hz,1H),7.22-7.28(m,5H),7.39-7.42(m,1H);13CNMR(CDCl3,75MHz)δ26.7,33.4,52.3,56.4,109.8,114.8,126.2,127.4,128.6,129.2,130.5,131.5,132.1,135.6,135.8,142.3,164.8,174.6;IR(KBr)ν1711,1605,1474,1306,1147,1098,812cm-1.HRMS(ESI)Calcd.forC20H18BrNNaO3S[M+Na]+:454.0083;Found:454.0067.
采用本实施例制备化合物16:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.62(s,3H),3.64(s,3H),3.76(d,J=12.0Hz,1H),4.04(d,J=12.0Hz,1H),6.76-6.84(m,4H),7.18-7.24(m,6H);13CNMR(CDCl3,75MHz)δ29.8,33.5,52.3,56.3,115.6,121.5,123.0,127.3,128.5,129.2,131.1,131.3,131.5,135.8,139.2,164.8,175.2;IR(KBr)ν1728,1601,1466,1319,1151,734,693cm-1.HRMS(ESI)Calcd.forC20H18ClNNaO3S[M+Na]+:410.0588;Found:410.0593.
采用本实施例制备化合物17:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ2.26(s,3H),3.29(s,3H),3.63(s,3H),3.79(d,J=12.0Hz,1H),4.06(d,J=10.2Hz,1H),6.74-6.81(m,4H),7.09(d,J=7.8Hz,1H),7.21-7.26(m,5H);13CNMR(CDCl3,75MHz)δ20.9,26.6,33.4,52.1,56.7,108.1,123.7,127.1,128.4,129.1,129.6,130.8,131.9,136.2,140.9,165.0,175.1;IR(KBr)ν1711,1499,1143,1086,804,693cm-1.HRMS(ESI)Calcd.forC21H21NNaO3S[M+Na]+:390.1134;Found:390.1149.
采用本实施例制备化合物18:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.30(s,3H),3.60(s,3H),3.74(s,3H),3.76(d,J=12.0Hz,1H),4.03(d,J=12.0Hz,1H),6.79-6.87(m,5H),6.99(d,J=6.6Hz,2H),7.18(d,J=8.1Hz,2H),7.26-7.30(m,1H);13CNMR(CDCl3,75MHz)δ26.4,32.7,52.0,55.0,56.6,108.2,113.8,122.2,122.8,127.9,128.6,129.1,130.2,130.7,136.1,143.2,158.7,164.8,175.0;IR(KBr)ν1707,1609,1515,1257,1082,1257,1082,1012,742,681cm-1.HRMS(ESI)Calcd.forC21H21NNaO4S[M+Na]+:406.1083;Found:406.1094.
采用本实施例制备化合物19:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ2.53(s,1H),2.75-2.83(m,1H),2.95-3.04(m,1H),3.28(s,3H),3.58(s,3H),3.64-3.67(m,2H),6.76(d,J=9.0Hz,2H),6.87(d,J=7.8Hz,1H),6.96-7.00(m,2H),7.27-7.32(m,1H);13CNMR(CDCl3,75MHz)δ26.6,32.1,52.2,55.4,61.2,108.5,122.6,123.0,129.0,129.4,131.1,136.5,143.1,164.9,175.9;IR(KBr)ν3437,1707,1605,1482,1384,1139,1077,763cm-1.HRMS(ESI)Calcd.forC15H17NNaO4S[M+Na]+:330.0770;Found:330.0772.
采用本实施例制备化合物20:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ2.45(s,1H),2.75-2.84(m,1H),2.96-3.04(m,1H),3.28(s,3H),3.60(s,3H),3.67(s,2H),6.74-6.81(m,4H),6.96-7.03(m,1H);13CNMR(CDCl3,75MHz)δ26.8,32.1,52.3,55.5,61.2,109.0(d,J CF =8.0Hz),111.2(d,J CF =25.2Hz),115.6(d,J CF =23.4Hz),130.6(d,J CF =8.3Hz),131.5,136.2,139.1,160.0(d,J CF =240.0Hz),164.8,175.6;IR(KBr)ν3445,1728,1687,1495,1319,1172,824,558cm-1.HRMS(ESI)Calcd.forC15H16FNNaO4S[M+Na]+:348.0676;Found:348.0678.
采用本实施例制备化合物21:白色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ2.23(s,1H),2.80-2.86(m,1H),2.99-3.07(m,1H),3.29(s,3H),3.63(s,3H),3.68-3.72(m,2H),6.77(s,1H),6.81(d,J=7.8Hz,2H),6.99(s,1H),7.29(d,J=1.8Hz,1H);13CNMR(CDCl3,75MHz)δ26.8,32.2,52.4,55.3,61.3,109.5,123.6,127.8,129.3,130.7,131.7,136.1,141.7,164.8,175.5;IR(KBr)ν3445,1715,1699,1597,1503,1147,820,546cm-1.HRMS(ESI)Calcd.forC15H16ClNNaO4S[M+Na]+:364.0381;Found:364.0386.
采用本实施例制备化合物22:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ2.23-2.27(m,1H),2.76-2.85(m,1H),2.97-3.05(m,1H),3.27(s,3H),3.62(s,3H),3.66-3.72(m,2H),6.74-6.76(m,2H),6.80(s,1H),7.11(d,J=1.8Hz,1H),7.40-7.43(m,1H);13CNMR(CDCl3,75MHz)δ26.8,32.1,52.4,55.2,61.3,110.0,115.0,126.3,131.0,131.7,132.2,136.1,142.2,164.8,175.4;IR(KBr)ν3448,1719,1695,1609,1490,1311,1151,1102,816,542cm-1.HRMS(ESI)Calcd.forC15H16BrNNaO4S[M+Na]+:407.9876;Found:407.9884.
采用本实施例制备化合物23:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ2.27(s,3H),2.34(s,1H),2.76-2.85(m,1H),2.97-3.06(m,1H),3.28(s,3H),3.60(s,3H),3.67-3.68(m,2H),6.74-6.82(m,4H),7.08-7.11(m,1H);13CNMR(CDCl3,75MHz)δ21.0,26.7,32.2,52.2,55.5,61.4,108.2,123.8,128.9,129.7,131.0,132.2,136.7,140.7,165.0,175.9;IR(KBr)ν3449,1724,1687,1605,1495,1437,1367,1311,1102,824,697,562cm-1.HRMS(ESI)Calcd.forC16H19NNaO4S[M+Na]+:344.0927;Found:344.0842.
采用本实施例制备化合物24:淡黄色固体，核磁共振和高分辨质谱测试等结果如下：1HNMR(300MHz,CDCl3)δ3.26(s,3H),3.56(d,J=15.9Hz,1H),3.59(s,3H),3.77(d,J=15.9Hz,1H),5.12(s,2H),6.77(d,J=3.3Hz,2H),6.87(d,J=7.8Hz,1H),6.96-7.01(m,2H),7.26-7.35(m,6H);13CNMR(CDCl3,75MHz)δ26.5,31.3,52.2,55.2,67.1,108.5,122.4,123.1,128.0,128.2,128.3,128.4,129.6,131.1,135.2,135.9,143.3,164.7,169.1,174.9;IR(KBr)ν1703,1601,1491,1139,975,751cm-1.HRMS(ESI)Calcd.forC22H21NNaO5S[M+Na]+:434.1033;Found:434.1031.
本发明的实施例2：化合物1:在圆底烧瓶中，先加入5毫升有机溶剂甲苯，再依次加入3-(2-丙烯酸甲酯)-3-OBoc-N-苯基氧化吲哚0.3mmol（122.7mg），苄氧羰基亚甲基硫醇0.4mmol（72.8mg），β-ICD9.3mg（10mmol%），室温搅拌反应，TLC检测反应完全后，反应液直接硅胶柱层析（300-400目）分离（石油醚：乙酸乙酯=10：1），得到淡黄色油状物。产率：86%。
采用本实施例制备，投料比与化合物1相同，可分别得到化合物2（产率78%），化合物3（产率81%），化合物4（产率75%），化合物5（产率82%），化合物6（产率76%），化合物7（产率74%），化合物8（产率75%），化合物9（产率78%），化合物10（产率81%），化合物11（产率82%），化合物12（产率84%），化合物13（产率75%），化合物14（产率76%），化合物15（产率77%），化合物16（产率75%），化合物17（产率74%），化合物18（产率76%），化合物19（产率76%），化合物20（产率71%），化合物21（产率74%），化合物22（产率72%），化合物23（产率76%），化合物24（产率70%）。

Claims (3)

1.一种3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物的制备方法，其特征在于：3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物具有如下通式（Ⅰ）的结构：
式（Ⅰ）中，R1为烷基、不同取代的芳基或不同取代的酯基；R2为不同取代的酯基，R3为烷基、不同取代的芳基或不同取代的酯基,R4为氢、卤素或烷基；
将3-(2-丙烯酸酯)-3-OBoc氧化吲哚化合物与烷基硫醇在碱性有机催化剂条件下，按摩尔比为4:3的比例在有机溶剂中进行加成消除反应，获得3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物；所述的碱性有机催化剂为DABCO、β-6’-羟基异辛克宁、β-6’-羟基异辛克宁衍生的有机碱或DABCO衍生的有机碱，碱性催化剂的加入量为氧化吲哚摩尔量的1-100%。
2.根据权利要求1所述的3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物的制备方法，其特征在于：所述的有机溶剂为乙腈、甲醇、乙醇、丙醇、异丙醇、乙醚、四氢呋喃、苯、甲苯、二甲苯、三甲苯、二氧六环、乙二醇二甲醚、异丙醚、氯仿、二氯甲烷或硝基苯。
3.根据权利要求1所述的3-(2-丙烯酸酯)-3-硫代氧化吲哚化合物的制备方法，其特征在于：3-(2-丙烯酸酯)-3-OBoc氧化吲哚化合物和烷基硫醇反应温度为25-100℃，反应时间为0.1-10小时。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101166722A (zh) * 2005-04-29 2008-04-23 惠氏公司 制备3,3-二取代的羟吲哚和硫代羟吲哚的方法
CN102070509A (zh) * 2011-01-24 2011-05-25 华东师范大学 一种制备3-烯丙基-3-羟基氧化吲哚的方法
CN102382031A (zh) * 2011-08-16 2012-03-21 河北博伦特药业有限公司 3-取代烯丙基酯氧化吲哚及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101166722A (zh) * 2005-04-29 2008-04-23 惠氏公司 制备3,3-二取代的羟吲哚和硫代羟吲哚的方法
CN102070509A (zh) * 2011-01-24 2011-05-25 华东师范大学 一种制备3-烯丙基-3-羟基氧化吲哚的方法
CN102382031A (zh) * 2011-08-16 2012-03-21 河北博伦特药业有限公司 3-取代烯丙基酯氧化吲哚及其制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
A facile approach for the asymmetric synthesis of oxindoles with a 3-sulfenylsubstituted quaternary stereocenter;Xiaowei Dou等;《Organic letters》;20130925;第15卷(第19期);第S2页最后一行至第S3页第8行 *
Catalytic asymmetric synthesis of 3-hydroxyl-2-oxindoles via enantioselective Morita-Baylis-Hillman reaction of isatins;Ci-Ci Wang等;《Tetrahedron》;20110222;第67卷(第16期);第2974页左栏第1段，第2976页表4 *

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