CN108516981A - 一种四氢喹啉螺环己二烯酮骨架化合物的合成方法 - Google Patents

一种四氢喹啉螺环己二烯酮骨架化合物的合成方法 Download PDF

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CN108516981A
CN108516981A CN201810730891.4A CN201810730891A CN108516981A CN 108516981 A CN108516981 A CN 108516981A CN 201810730891 A CN201810730891 A CN 201810730891A CN 108516981 A CN108516981 A CN 108516981A
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肖建
李帅帅
朱帅
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Qingdao Agricultural University
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Abstract

本发明涉及合成四氢喹啉螺环己二烯酮骨架化合物的方法，酚类化合物与氨基苯甲醛类化合物在六氟异丙醇的存在下，经历氮原子α位氢迁移，最终得到去芳香化产物。本发明提供的合成方法，首次实现以芳香化为驱动力的氢迁移反应。原料简单易得；在室温下即可反应，反应条件温和，无需金属或质子催化剂，操作方便，经济高效；本发明方法的反应活性高，产率高达98％，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

一种四氢喹啉螺环己二烯酮骨架化合物的合成方法
技术领域
本发明属于化学合成技术领域，具体涉及一种四氢喹啉螺环己二烯酮骨架化合物的合成方法。
背景技术
大量含螺环的四氢喹啉骨架手性化合物广泛存在与天然产物和药物中，他们含有众多重要的生物活性，因而引起了人们的浓厚兴趣。将“去芳构化”反应串联反应巧妙结合，可以从简单的芳香化合物出发高效高选择性地合成一些复杂甚至具有多维结构的分子。合成环己二烯酮螺环骨架的方法主要是以苯酚或萘酚的去芳香化反应为主，该类反应常用高价碘试剂或者过渡金属，价格昂贵，操作复杂；生成四氢喹啉螺环可以通过串联[1,5]-氢迁移/环化来实现，当前该策略大多需要路易斯酸或者布朗斯特酸来催化，或者需要高温条件。
2002年，英国科学家报道了一种四氢喹啉螺环己二烯酮的合成方法(2,8’-Disubstituted-1,1’-Binaphthyls:A New Pattern in Chiral Ligands,Chem.Eur.J.2002,8,4633-4648)，该方法以2-甲氧基-1-萘基硼酸和1,8-二溴基萘为起始原料，在贵重金属钯等为催化剂通过五步反应构建了目标化合物。然而该方法操作复杂，步骤冗长，采用贵重过渡金属催化剂等成本高，条件苛刻。
图1以钯为催化剂构建四氢喹啉螺环己二烯酮
过渡金属在上述领域中表现处巨大的潜力，可以合成药物分子中常见骨架如螺环、联苯、金属有机化合物等。但是这类反应依然存在一些显著的问题：(1)需要用价格昂贵的过渡金属催化剂，如铑和钯等，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；(2)反应条件较为苛刻，需要加入额外的氧化剂和添加剂，并需要较高的反应温度；(3)绝大多数反应在克级规模上效果不佳，底物适用范围偏窄以及较难实现不对称催化；(4)需要额外的导向基团与金属进行配位导向，而导向基团往往在反应完成后需要脱去。因此这类合成策略的原子经济性不高。
中国专利CN201711248907.X和CN201711254567.1公开了在酸性条件下，利用氢迁移策略，生成亚胺正离子，分别借助樟脑磺酸、联萘酚磷酸两种非过渡金属催化剂，生成苯并氮杂环化合物二苯并[b,e]吖庚因类化合物、八氢二吡咯并喹啉骨架化合物。这两种利用氮原子α位氢迁移构建苯并氮杂环(例如四氢喹啉)衍生物的方法，受限于苄醇在酸性条件下的脱水反应得到碳正离子，以此驱动氢迁移发生；且生成的亚胺正离子与另一苯环发生傅克反应，无法实现芳香化合物的“去芳构化”。
目前的众多氢迁移合成策略中，串联氢迁移/环化反应大多无法构建环己二烯酮结构，此外，该反应还存在其他竞争反应，例如，羟基邻位进攻氢迁移生成的亚胺正离子可以构建七元环，羟基进攻该正离子可以生成八元环，这些均不能实现去芳香化反应。
因此，为了克服现有技术中的上述问题，需要一种新的四氢喹啉螺环己二烯酮的合成方法，以改善反应的原子经济性、步骤经济性和环境友好性。
发明内容
本发明的目的在于提供一种新的四氢喹啉螺环己二烯酮骨架化合物的合成方法。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，具体的：
由苯酚类或萘酚类化合物A与氨基甲醛类化合物B进行反应即得所述四氢喹啉螺环己二烯酮化合物，其反应在醇溶剂、甲苯和1,2-二氯乙烷DCE一种或几种中进行。
所述四氢喹啉螺环己二烯酮骨架化合物为式Ⅰ、式Ⅱ、式Ⅲ和式Ⅳ所示化合物中任意一种：
其中
式Ⅰ、式Ⅱ、式Ⅲ、式Ⅳ中，虚线表示任选的单键；
n为1或2；
X选自碳和氮；
Y1、Y2独立地选自氢、氧、碳、甲氧基、二乙胺基、四氢吡咯、哌啶中任意一种；当Y1、Y2独立地选自氧、碳时，Y1、Y2构成环结构；
R1选自甲氧基、二乙胺基、四氢吡咯基、哌啶基中任意一种；并且
R2选自氢、氟、氯、溴、甲基、三氟甲基、硝基、甲氧基、氰基、对苯乙酰基、对甲氧基苯乙炔基、噻吩基、硼酸脂、丙烯酸甲酯中任意一种。
所述苯酚类或萘酚类化合物A为式Ⅴ所示化合物中任意一种，
所述氨基甲醛类化合物B为式Ⅵ、式Ⅶ所示化合物中任意一种：
其中
式Ⅴ、式Ⅵ、式Ⅶ中，虚线表示任选的单键；
n为1或2；
X选自碳和氮；
Y1、Y2独立地选自氢、氧、碳、甲氧基、二乙胺基、四氢吡咯基、哌啶基中任意一种；当Y1、Y2独立地选自氧、碳时，Y1、Y2构成环结构；
R1选自甲氧基、二乙胺基、四氢吡咯基、哌啶基中任意一种；并且
R2选自氢、氟、氯、溴、甲基、三氟甲基、硝基、甲基、甲氧基、氰基、对苯乙酰基、对甲氧基苯乙炔基、噻吩基、硼酸脂、丙烯酸甲酯中任意一种。
所述醇溶剂为三氟乙醇、六氟异丙醇、甲醇、异丙醇中任意一种。
所述反应在0℃-120℃条件下反应。
所述化合物A与化合物B的摩尔比为1.1-1.5:1。
本发明提供了式Ⅰ、式Ⅱ、式Ⅲ和式Ⅳ所示化合物的合成方法，包括以下步骤：
将化合物A和化合物B加入到六氟异丙醇或六氟异丙醇与甲苯的混合溶液中，搅拌反应，通过薄层色谱法检测反应情况，反应完毕进行浓缩、纯化，制得四氢喹啉螺环己二烯酮骨架化合物。
所述六氟异丙醇与甲苯的混合溶液，两者体积比为1:1。
本发明的技术方案取得了如下有益效果：酚类化合物与氨基苯甲醛类化合物在六氟异丙醇的存在下首先发生亲核加成生成苄醇类化合物，随后脱水，生成的去芳香化产物邻亚甲基苯醌作为氮原子α位氢迁移的受体接受氢负离子，再恢复芳香化得到两性离子，亚胺正离子受到富电子芳环的进攻最终得到去芳香化产物。
图2串联氢迁移/环化反应构建环己二烯酮结构
本发明提供了一种合成四氢喹啉螺环己二烯酮骨架化合物的方法，首次实现以芳香化为驱动力的氢迁移反应，以及邻亚甲基苯醌作为氢受体的氢迁移反应。目前对酚类化合物进行的去芳香化改造反应，由于酚的亲核性较弱，通过酚邻位预先占位，随后通过亲电进攻实现去芳香化，相比之下，本发明的合成方法不需预先合成占位基团，且不需进行氟取代以借其活化醛基。该反应在室温下即可进行，反应条件温和，无需金属或质子催化剂，操作方便，经济高效；反应活性高，产率高达98％，原料转化完全；产物分离方便，具有绿色经济性，对环境友好。
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
化合物A1化合物B1
设立17组平行试验组，将化合物A1(芝麻酚)和化合物B1(2-吡咯烷基苯甲醛)按摩尔比1.3:1加入反应瓶中，加入添加剂和1mL的溶剂，使反应体系中化合物B1浓度分别为0.05M、0.1M、0.2M。反应溶剂分别为1,2-二氯乙烷DCE、三氟乙醇TFE、六氟异丙醇HFIP、异丙醇iPrOH、甲醇MeOH。
反应在25℃下通过搅拌进行，通过TLC薄层色谱分析确定反应情况。待反应结束后，将反应产物进行旋蒸浓缩、硅胶柱上纯化分离。
利用上述反应式，各平行试验组使用不同的添加剂和溶剂，具体使用的添加剂、溶剂种类和浓度如表1所示：
表1.化合物A1与化合物B1反应产率表
注：产率为分离产率；第12组中添加剂HFIP浓度为0.1M；第16组中溶剂HFIP用量0.5mL；第17组中溶剂HFIP用量2mL。
由此可见，使用HFIP作为本发明方法的溶剂，可以明显的提高产物的产率。
实施例2
设立4组平行试验组，按照不同摩尔比加入化合物A1和化合物B1于反应瓶中，加入2mL溶剂HFIP。反应在25℃下通过搅拌进行，通过TLC薄层色谱分析确定反应情况。待反应结束后，将反应产物进行旋蒸浓缩、硅胶柱上纯化分离。
利用实施例1的反应式和操作步骤，反应产率如表2：
表2.化合物A1与化合物B1不同摩尔比反应产率表
注：产率为分离产率。
下列实施例3-34中，化合物A与化合物B按原料摩尔比1.3:1进行反应。
实施例3
原料：芝麻酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H17NO3
精确分子量：295.1208
分子量：295.3380
结构式：
产率：88％
1H核磁共振(500MHz,CDCl3)δ7.14(t,J＝7.7Hz,1H),7.02(d,J＝7.3Hz,1H),6.60(t,J＝7.3Hz,1H),6.51(d,J＝8.1Hz,1H),5.82(s,1H),5.80(s,1H),5.71(s,1H),5.20(s,1H),3.75(dd,J＝9.8,5.4Hz,1H),3.52–3.44(m,1H),3.38(d,J＝15.5Hz,1H),3.19(dd,J＝16.3,8.7Hz,1H),2.69(d,J＝15.6Hz,1H),1.99(dd,J＝5.8,3.7Hz,1H),1.96–1.85(m,2H),1.46–1.35(m,1H)；13C核磁共振((126MHz,CDCl3)δ201.2,163.8,145.18,142.9,129.3,127.6,119.2,115.36,110.4,104.6,101.5,99.3,65.43,48.4,47.11,41.1,27.5,23.5.高分辨质谱分析(ESI):calcd.for C18H17NO3[M+H]+:296.1287,实际值:296.1295.
实施例4
原料：芝麻酚、2-吡咯烷基-3-氯苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H16ClNO3
精确分子量：329.0819
分子量：329.7800
结构式：
产率：39％
1H核磁共振(500MHz,CDCl3)δ7.18(d,J＝7.7Hz,1H),6.92(d,J＝7.4Hz,1H),6.68(dd,J＝15.8,8.3Hz,1H),5.86(s,1H),5.82(s,1H),5.75(s,1H),5.26(s,1H),4.33(dd,J＝17.2,8.1Hz,1H),3.81(d,J＝5.8Hz,1H),3.45(d,J＝16.0Hz,1H),3.32(td,J＝9.2,4.5Hz,1H),2.68(d,J＝16.0Hz,1H),2.05–1.99(m,1H),1.90(td,J＝8.1,3.9Hz,1H),1.84–1.74(m,1H),1.58–1.45(m,1H)；13C核磁共振(126MHz,CDCl3)δ201.3,164.1,144.7,141.4,129.7,128.1,124.2,121.4,119.0,104.6,101.6,99.8,66.9,53.1,48.8,41.5,27.8,24.8.高分辨质谱分析(ESI):calcd.for C18H16ClNO3[M+H]+:380.1498,实际值:380.1494.
实施例5
原料：芝麻酚、4-甲基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C19H19NO3
精确分子量：309.1365
分子量：309.3650
结构式：
产率：71％
1H核磁共振(500MHz,CDCl3)δ6.91(d,J＝7.5Hz,1H),6.43(d,J＝7.4Hz,1H),6.33(s,1H),5.80(d,J＝9.4Hz,2H),5.70(s,1H),5.22(s,1H),3.73(dd,J＝9.8,5.4Hz,1H),3.52–3.43(m,1H),3.33(d,J＝15.4Hz,1H),3.18(dd,J＝16.2,8.8Hz,1H),2.66(d,J＝15.5Hz,1H),2.31(s,3H),1.98(dt,J＝10.6,4.2Hz,1H),1.95–1.81(m,2H),1.39(dd,J＝9.9,8.0Hz,1H)；13C核磁共振(126MHz,CDCl3)δ201.3,163.8,145.1,142.7,137.3,129.1,116.3,116.2,111.1,104.7,101.5,99.3,65.4,48.6,47.1,40.8,27.5,23.5,21.6.高分辨质谱分析(ESI):calcd.for C19H19NO3[M+H]+:310.1443,实际值:310.1445.
实施例6
原料：芝麻酚、4-三氟甲基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C19H16F3NO3
精确分子量：363.1082
分子量：363.3362
结构式：
产率：84％
1H核磁共振(500MHz,CDCl3)δ7.09(d,J＝7.6Hz,1H),6.82(d,J＝7.5Hz,1H),6.68(s,1H),5.82(d,J＝10.7Hz,2H),5.73(s,1H),5.11(s,1H),3.76(dd,J＝9.6,5.1Hz,1H),3.51(t,J＝8.3Hz,1H),3.37(d,J＝15.8Hz,1H),3.21(d,J＝8.0Hz,1H),2.72(d,J＝15.8Hz,1H),2.02(t,J＝6.4Hz,1H),1.99–1.84(m,2H),1.51–1.37(m,1H)；13C核磁共振(126MHz,CDCl3)δ200.7,163.9,145.5,142.8,130.3,130.0,129.7,129.5(d,J＝12.1Hz),125.7,123.5,122.8,111.7(q,J＝3.9Hz),106.5(q,J＝3.8Hz),103.7,101.6,99.4,65.4,53.5,47.6,47.2,40.8,27.5,23.4.高分辨质谱分析(ESI):calcd.for C19H16F3NO3[M+H]+:364.1161,实际值:364.1157.
实施例7
原料：芝麻酚、4-氰基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C19H16N2O3
精确分子量：320.1161
分子量:320.3480
结构式：
产率：75％
1H核磁共振(500MHz,CDCl3)δ7.07(d,J＝7.6Hz,1H),6.86(d,J＝7.6Hz,1H),6.69(s,1H),5.84(d,J＝10.8Hz,2H),5.73(s,1H),5.05(s,1H),3.74(dd,J＝10.0,5.3Hz,1H),3.47(t,J＝8.3Hz,1H),3.36(d,J＝16.1Hz,1H),3.17(dd,J＝16.6,8.7Hz,1H),2.71(d,J＝16.1Hz,1H),2.11–2.00(m,1H),2.00–1.84(m,2H),1.42(dd,J＝10.0,8.3Hz,1H)；13C核磁共振(126MHz,CDCl3)δ200.2,163.9,145.7,143.0,129.7,124.6,119.8,118.8,112.7,111.1,103.2,101.7,99.4,65.34,47.3,47.2,40.9,27.4,23.4.高分辨质谱分析(ESI):calcd.forC19H16N2O3[M+H]+:321.1239,实际值:321.1240.
实施例8
原料：芝麻酚、2-吡咯烷基-4-氯苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H16ClNO3
精确分子量：329.0819
分子量：329.7800
结构式：
产率：82％
1H核磁共振500MHz,CDCl3)δ6.91(d,J＝7.9Hz,1H),6.55(dd,J＝7.9,1.8Hz,1H),6.46(d,J＝1.7Hz,1H),5.81(d,J＝10.2Hz,2H),5.71(s,1H),5.12(s,1H),3.73(dd,J＝10.0,5.4Hz,1H),3.50–3.39(m,1H),3.29(d,J＝15.5Hz,1H),3.15(dd,J＝16.3,8.9Hz,1H),2.64(d,J＝15.6Hz,1H),2.07–1.97(m,1H),1.92(ddd,J＝15.1,11.9,7.9Hz,2H),1.39(dd,J＝10.1,7.9Hz,1H)；13C核磁共振(126MHz,CDCl3)δ200.8,163.9,145.4,143.7,133.01,130.1,117.6,115.1,110.0,103.9,101.6,99.3,65.3,47.9,47.2,40.6,27.5,23.4.高分辨质谱分析(ESI):calcd.for C18H16ClNO3[M+H]+:330.0897,实际值:330.0899.
实施例9
原料：芝麻酚、4-溴-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H16BrNO3
精确分子量：373.0314
分子量：374.2340
结构式：
产率：84％
1H核磁共振(500MHz,CDCl3)δ6.86(d,J＝7.9Hz,1H),6.70(dd,J＝7.9,1.6Hz,1H),6.61(d,J＝1.4Hz,1H),5.82(d,J＝9.6Hz,2H),5.71(s,1H),5.13(s,1H),3.73(dd,J＝10.0,5.4Hz,1H),3.50–3.40(m,1H),3.27(d,J＝15.5Hz,1H),3.15(dd,J＝16.3,9.0Hz,1H),2.64(d,J＝15.6Hz,1H),2.00(dd,J＝11.4,4.2Hz,1H),1.92(ddd,J＝15.3,11.9,7.9Hz,2H),1.39(dd,J＝10.1,7.9Hz,1H)；13C核磁共振(126MHz,CDCl3)δ200.8,163.9,145.4,143.9,130.4,121.2,118.1,117.9,112.9,103.9,101.6,99.3,65.3,47.9,47.2,40.6,27.5,23.4.高分辨质谱分析(ESI):calcd.for C18H16BrNO3[M+H]+:374.0397,实际值:374.0399.
实施例10
原料：芝麻酚、4-硼酸酯基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C24H29BNO5
精确分子量：421.2061
分子量：421.3000
结构式：
产率：70％
1H核磁共振(500MHz,CDCl3)δ7.11–6.99(m,2H),6.95(s,1H),5.80(d,J＝9.6Hz,2H),5.70(s,1H),5.18(s,1H),3.79–3.69(m,1H),3.57(s,1H),3.39(d,J＝15.8Hz,1H),3.26(d,J＝7.8Hz,1H),2.70(d,J＝15.8Hz,1H),1.96(d,J＝10.3Hz,1H),1.90(dd,J＝15.9,10.1Hz,2H),1.40(d,J＝8.9Hz,1H),1.34(s,12H)；13C核磁共振(126MHz,CDCl3)δ201.2,163.9,145.2,142.4,128.8,122.6,122.0,116.3,104.6,101.5,99.3,83.6,65.6,48.3,47.3,41.3,27.5,24.9,24.8,23.5.高分辨质谱分析(ESI)::calcd.for C24H29BNO5[M+H]+:422.2139,实际值:422.2143.
实施例11
原料：芝麻酚、4-丙烯酸甲脂基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C22H21NO5
精确分子量：379.1420
分子量：379.4120
结构式：
产率：93％
1H核磁共振(500MHz,CDCl3)δ7.65(d,J＝16.0Hz,1H),7.03(d,J＝7.6Hz,1H),6.79(d,J＝7.5Hz,1H),6.62(s,1H),6.40(d,J＝16.0Hz,1H),5.82(d,J＝10.3Hz,2H),5.72(s,1H),5.15(s,1H),3.80(s,3H),3.75(dd,J＝9.9,5.3Hz,1H),3.50(t,J＝7.9Hz,1H),3.37(d,J＝15.9Hz,1H),3.21(dd,J＝16.3,8.8Hz,1H),2.70(d,J＝16.0Hz,1H),2.09–1.99(m,1H),1.99–1.81(m,2H),1.48–1.34(m,1H)；13C核磁共振(126MHz,CDCl3)δ200.8,167.7,163.9,145.8,145.4,143.1,133.7,129.7,122.2,116.6,115.6,109.3,104.1,101.6,99.3,65.4,51.6,48.1,47.1,41.0,27.5,23.5.高分辨质谱分析(ESI):calcd.for C22H21NO5[M+H]+:380.1498,实际值:380.1494.
实施例12
原料：芝麻酚、4-对甲氧基苯乙炔基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C27H23NO4
精确分子量：425.1627
分子量：425.4840
结构式：
产率：81％
1H核磁共振(500MHz,CDCl3)δ7.47(d,J＝8.6Hz,2H),6.98(d,J＝7.6Hz,1H),6.87(d,J＝8.6Hz,2H),6.77(d,J＝7.6Hz,1H),6.65(s,1H),5.81(d,J＝9.6Hz,2H),5.71(s,1H),5.16(s,1H),3.83(s,3H),3.76(dd,J＝9.8,5.3Hz,1H),3.49(t,J＝8.0Hz,1H),3.37(d,J＝15.7Hz,1H),3.20(d,J＝7.7Hz,1H),2.69(d,J＝15.8Hz,1H),2.02(dd,J＝13.0,3.2Hz,1H),1.93(ddd,J＝15.5,11.4,7.1Hz,2H),1.47–1.34(m,1H)；13C核磁共振(126MHz,CDCl3)δ201.0,163.9,159.5,145.3,142.6,133.0,129.2,122.4,119.7,118.8,115.7,113.9,112.9,104.3,101.5,99.3,88.9,88.1,65.4,55.3,48.2,47.2,41.0,27.5,23.5.高分辨质谱分析(ESI):calcd.for C27H23NO4[M+H]+:426.1705,实际值:426.1694.
实施例13
原料：芝麻酚、4-对苯乙酰基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C26H23NO4
精确分子量：413.1627
分子量：413.4730
结构式：
产率：84％
1H核磁共振(500MHz,CDCl3)δ8.02(d,J＝8.2Hz,2H),7.69(d,J＝8.2Hz,2H),7.12(d,J＝7.7Hz,1H),6.86(d,J＝7.6Hz,1H),6.72(s,1H),5.82(d,J＝9.6Hz,2H),5.73(s,1H),5.24(s,1H),3.80(dd,J＝9.8,5.3Hz,1H),3.57(t,J＝8.0Hz,1H),3.41(d,J＝15.6Hz,1H),3.27(d,J＝7.8Hz,1H),2.75(d,J＝15.7Hz,1H),2.64(s,3H),2.03(d,J＝7.3Hz,1H),1.95(ddd,J＝15.5,11.5,7.1Hz,2H),1.50–1.37(m,1H)；13C核磁共振(126MHz,CDCl3)δ201.0,197.8,163.9,146.6,145.4,143.2,139.4,135.6,129.8,128.8,127.2,119.6,114.5,108.9,104.3,101.6,99.4,65.5,48.3,47.2,40.8,27.5,26.7,23.5.高分辨质谱分析(ESI):calcd.for C26H23NO4[M+H]+:414.1705,实际值:414.1707.
实施例14
原料：芝麻酚、4-噻吩基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C22H19NO3S
精确分子量：377.1086
分子量：377.4580
结构式：
产率：88％
1H核磁共振(500MHz,CDCl3)δ7.28(d,J＝3.4Hz,1H),7.24(d,J＝5.0Hz,1H),7.13–7.05(m,1H),7.03(d,J＝7.7Hz,1H),6.87(d,J＝7.6Hz,1H),6.72(s,1H),5.81(d,J＝9.7Hz,2H),5.72(s,1H),5.22(s,1H),3.78(dd,J＝9.8,5.4Hz,1H),3.55(dd,J＝12.1,4.9Hz,1H),3.37(d,J＝15.6Hz,1H),3.25(t,J＝8.3Hz,1H),2.71(d,J＝15.7Hz,1H),2.01(dd,J＝11.0,3.9Hz,1H),1.93(ddd,J＝16.1,11.5,4.4Hz,2H),1.50–1.35(m,1H)；13C核磁共振(126MHz,CDCl3)δ201.1,163.9,145.3,145.3,143.1,133.8,129.7,127.8,124.2,122.7,118.9,113.5,107.8,104.4,101.5,99.3,65.5,48.4,47.2,40.9,27.5,23.5.高分辨质谱分析(ESI):calcd.for C22H19NO3S[M+H]+:378.1164,实际值:378.1160.
实施例15
原料：芝麻酚、5-甲氧基-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C19H19NO4
精确分子量：325.1314
分子量：325.3640
结构式：
产率：80％
1H核磁共振(500MHz,CDCl3)δ6.75(d,J＝8.6Hz,1H),6.66(s,1H),6.46(d,J＝8.7Hz,1H),5.81(d,J＝10.3Hz,2H),5.70(s,1H),5.21(s,1H),3.74(s,3H),3.69(dd,J＝9.4,5.3Hz,1H),3.41(dd,J＝16.3,12.4Hz,2H),3.25–3.09(m,1H),2.65(d,J＝15.7Hz,1H),1.92(ddd,J＝20.3,12.0,6.5Hz,3H),1.50–1.33(m,1H)；13C核磁共振(126MHz,CDCl3)δ201.2,163.8,150.5,145.2,137.7,120.3,115.5,113.2,111.3,104.7,101.5,99.3,65.7,55.9,48.8,47.6,41.1,27.4,23.5.高分辨质谱分析(ESI):calcd.for C19H19NO4[M+H]+:326.1392,实际值:326.1390.
实施例16
原料：芝麻酚、5-氯-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H16ClNO3
精确分子量：329.0819
分子量：329.7800
结构式：
产率：77％
1H核磁共振(500MHz,CDCl3)δ7.07(d,J＝8.5Hz,1H),6.99(s,1H),6.41(d,J＝8.6Hz,1H),5.82(d,J＝8.8Hz,2H),5.71(s,1H),5.12(s,1H),3.72(dd,J＝9.5,5.1Hz,1H),3.45(t,J＝8.4Hz,1H),3.33(d,J＝15.7Hz,1H),3.15(dd,J＝16.2,8.3Hz,1H),2.63(d,J＝15.7Hz,1H),2.07–1.82(m,3H),1.47–1.33(m,1H)；13C核磁共振(126MHz,CDCl3)δ200.8,163.9,145.4,141.4,128.8,127.3,120.7,119.9,111.3,103.9,101.6,99.3,65.5,47.9,47.3,40.8,27.5,23.5.高分辨质谱分析(ESI):calcd.for C18H16ClNO3[M+Na]+:352.0716,实际值:352.0714.
实施例17
原料：芝麻酚、5-硝基-2-吡咯烷基苯甲醛
反应条件：40℃/HFIP
产物：化学式：C18H16N2O5
精确分子量：340.1059
分子量：340.3350
结构式：
产率：68％
1H核磁共振(500MHz,CDCl3)δ8.07(dd,J＝9.0,2.4Hz,1H),7.97(s,1H),6.46(d,J＝9.1Hz,1H),5.85(d,J＝6.2Hz,2H),5.75(s,1H),5.03(s,1H),3.87(dd,J＝10.5,5.2Hz,1H),3.62(t,J＝9.1Hz,1H),3.35(d,J＝15.6Hz,1H),3.29(dd,J＝17.1,9.7Hz,1H),2.75(d,J＝15.6Hz,1H),2.13–2.05(m,1H),1.98(ddd,J＝13.7,10.2,6.2Hz,2H),1.45(dd,J＝10.7,7.4Hz,1H)；13C核磁共振(126MHz,CDCl3)δ199.8,163.9,147.7,145.9,136.6,125.6,125.1,118.8,109.1,102.6,101.8,99.4,65.6,47.6,47.3,40.7,27.5,23.2.高分辨质谱分析(ESI):calcd.for C18H16N2O5[M+H]+:341.1059,实际值:341.1061.
实施例18
原料：芝麻酚、6-氟-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H16FNO3
精确分子量：313.1114
分子量：313.3284
结构式：
产率：98％
1H核磁共振(500MHz,CDCl3)δ7.06(dd,J＝15.0,7.9Hz,1H),6.35(t,J＝8.7Hz,1H),6.29(d,J＝8.2Hz,1H),5.81(d,J＝9.5Hz,2H),5.72(s,1H),5.16(s,1H),3.70(dd,J＝9.9,5.3Hz,1H),3.47(td,J＝9.1,2.2Hz,1H),3.20(dd,J＝16.3,8.7Hz,1H),3.07(d,J＝16.1Hz,1H),2.94(d,J＝16.0Hz,1H),2.06–1.96(m,1H),1.96–1.86(m,2H),1.41(dd,J＝9.6,8.2Hz,1H)；13C核磁共振(126MHz,CDCl3)δ200.9,163.9,162.5,160.6,145.4,144.3(d,J＝7.7Hz),127.9(d,J＝10.8Hz),106.4,104.1,102.2,102.1,101.6,99.4,64.8,47.5(d,J＝11.8Hz),33.5(d,J＝4.3Hz),27.5,23.4.高分辨质谱分析(ESI):calcd.for C18H16FNO3[M+H]+:314.1192,实际值:314.1193.
实施例19
原料：芝麻酚、6-氯-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H16ClNO3
精确分子量：329.0819
分子量：329.7800
结构式：
产率：82％
1H核磁共振(500MHz,CDCl3)δ7.04(t,J＝8.0Hz,1H),6.67(d,J＝7.9Hz,1H),6.41(d,J＝8.2Hz,1H),5.82(d,J＝7.8Hz,2H),5.73(s,1H),5.16(s,1H),3.70(dd,J＝9.8,5.3Hz,1H),3.46(td,J＝8.6,2.0Hz,1H),3.21(dd,J＝16.3,8.5Hz,1H),3.15(d,J＝16.4Hz,1H),3.06(d,J＝16.4Hz,1H),2.07–1.97(m,1H),1.97–1.84(m,2H),1.42(dd,J＝9.7,8.2Hz,1H)；13C核磁共振(126MHz,CDCl3)δ200.8,163.9,145.4,144.1,134.7,127.8,117.1,116.2,108.9,104.2,101.6,99.4,64.8,48.3,47.4,38.4,27.5,23.5.高分辨质谱分析(ESI):calcd.for C18H16ClNO3[M+H]+:330.0897,实际值:330.0893.
实施例20
原料：芝麻酚、6-溴-2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H16BrNO3
精确分子量：373.0314
分子量：374.2340
结构式：
产率：91％
1H核磁共振(500MHz,CDCl3)δ6.97(t,J＝8.0Hz,1H),6.86(d,J＝7.9Hz,1H),6.45(d,J＝8.1Hz,1H),5.83(d,J＝6.8Hz,2H),5.73(s,1H),5.17(s,1H),3.70(dd,J＝9.7,5.3Hz,1H),3.45(t,J＝8.9Hz,1H),3.21(d,J＝8.0Hz,1H),3.16(d,J＝16.5Hz,1H),3.03(d,J＝16.4Hz,1H),2.07–1.98(m,1H),1.97–1.85(m,2H),1.49–1.36(m,1H)；13C核磁共振(126MHz,CDCl3)δ200.7,164.0,145.4,144.2,128.3,125.6,119.5,118.7,109.5,104.1,101.6,99.4,64.9,48.5,47.3,41.4,27.4,23.6.高分辨质谱分析(ESI):calcd.forC18H16BrNO3[M+H]+:374.0392,实际值:374.0393.
实施例21
原料：芝麻酚、2-吡咯烷基-3-喹啉基甲醛
反应条件：120℃/甲苯：HFIP＝1:1
产物：化学式：C21H18N2O3
精确分子量：346.1317
分子量：346.3860
结构式：
产率：87％
1H核磁共振(500MHz,CDCl3)δ7.71(d,J＝8.4Hz,1H),7.60(s,1H),7.56–7.46(m,2H),7.17(t,J＝7.4Hz,1H),5.84(s,1H),5.81(s,1H),5.75(s,1H),5.19(s,1H),4.00(dd,J＝10.2,5.1Hz,1H),3.96(t,J＝9.5Hz,1H),3.64(dd,J＝13.9,5.1Hz,1H),3.47(d,J＝15.7Hz,1H),2.84(d,J＝15.5Hz,1H),2.03–1.98(m,1H),1.94(dd,J＝16.8,8.4Hz,2H),1.52–1.43(m,1H)；13C核磁共振(126MHz,CDCl3)δ200.1,163.9,152.4,145.7,135.1,129.0,127.0,125.8,122.9,121.8,118.0,103.2,101.7,99.3,65.4,48.5,46.7,40.9,28.1,23.2.高分辨质谱分析(ESI):calcd.for C21H18N2O3[M+H]+:347.1317,实际值:347.1319.
实施例22
原料：芝麻酚、2-全氢异吲哚基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C22H23NO3
精确分子量：349.1678
分子量：349.4300
结构式：
产率：52％；dr＝1.7:1
1H核磁共振(500MHz,CDCl3)δ7.13(t,J＝7.6Hz,3H),6.99(t,J＝7.3Hz,3H),6.56(dt,J＝14.4,7.3Hz,3H),6.50(d,J＝8.1Hz,1H),6.46(d,J＝8.1Hz,2H),5.83(d,J＝9.7Hz,3H),5.79(d,J＝2.9Hz,3H),5.71(d,J＝2.4Hz,2H),5.16(s,2H),5.13(s,1H),4.02(d,J＝9.6Hz,1H),3.68(d,J＝8.8Hz,2H),3.58(t,J＝7.9Hz,2H),3.35(d,J＝15.4Hz,1H),3.27(d,J＝15.3Hz,2H),3.22(d,J＝3.3Hz,2H),2.77–2.71(m,2H),2.68(dd,J＝15.4,4.9Hz,3H),2.11(s,1H),1.99–1.88(m,3H),1.80–1.64(m,7H),1.58(d,J＝4.7Hz,2H),1.48(dt,J＝7.9,4.1Hz,2H),1.38(dd,J＝23.2,10.9Hz,3H),1.25(t,J＝11.9Hz,4H),1.18–1.09(m,6H)；13C核磁共振(126MHz,CDCl3)δ201.9,201.5,163.94,163.7,151.3,148.2,144.8,144.6,143.3,142.7,141.2,129..0,127.7,127.6,118.8,118.6,114.9,114.6,110.0,109.3,108.1,106.7,105.4,105.1,101.5,101.5,101.1,99.3,99.1,98.3,70.3,65.5,53.8,51.8,47.8,47.6,43.2,42.4,42.4,40.8,37.3,29.6,28.9,28.6,26.7,25.7,25.2,21.6.高分辨质谱分析(ESI):calcd.for C22H23NO3[M+H]+:350.1756,实际值:350.1754.
实施例23
原料：芝麻酚、2-四氢异喹啉基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C23H19NO3
精确分子量：357.1365
分子量：357.4090
结构式：
产率：70％
1H核磁共振(500MHz,CDCl3)δ7.16(dd,J＝17.0,8.9Hz,2H),7.07(s,4H),6.79(d,J＝7.9Hz,1H),6.71(t,J＝6.6Hz,1H),5.65(s,1H),5.57(s,1H),5.54(s,2H),4.88(s,1H),3.94(d,J＝9.8Hz,1H),3.71(d,J＝16.1Hz,1H),3.32(t,J＝11.1Hz,1H),3.03(t,J＝11.1Hz,1H),2.84–2.65(m,2H)；13C核磁共振(126MHz,CDCl3)δ201.7,163.5,144.9,144.1,136.5,133.9,129.4,128.3,127.9,127.2,126.9,125.9,120.7,116.8,112.2,105.4,101.2,99.6,65.0,53.6,44.4,40.9,30.0.高分辨质谱分析(ESI):calcd.for C23H19NO3[M+H]+:358.1443,实际值:358.1441.
实施例24
原料：芝麻酚、8-吡咯烷基-1-萘基甲醛
反应条件：25℃/HFIP:甲苯＝1:1；两种反应物与哌啶(摩尔比8-吡咯烷基-1-萘基甲醛：哌啶＝1:2)在1.0mL甲苯中，120℃反应12h,冷却到25℃，再加入1.0mLHFIP反应10min；
产物：化学式：C22H19NO3
精确分子量：347.1521
分子量：347.4140
结构式：
产率：56％
1H核磁共振(500MHz,CDCl3)δ7.62(d,J＝7.9Hz,3H),7.29(dd,J＝13.4,6.8Hz,8H),7.04(d,J＝6.7Hz,1H),6.93(d,J＝6.8Hz,2H),6.72(d,J＝6.9Hz,3H),5.89(s,2H),5.87(s,2H),5.85(s,3H),5.76(s,1H),5.65(d,J＝9.2Hz,3H),4.40(d,J＝12.9Hz,1H),4.17(d,J＝9.4Hz,2H),3.54(dt,J＝15.3,8.2Hz,4H),3.46(d,J＝13.7Hz,2H),3.10(dd,J＝17.2,9.3Hz,3H),2.53(dd,J＝22.1,13.3Hz,3H),2.07(td,J＝12.4,6.2Hz,3H),2.03–1.96(m,2H),1.82–1.73(m,4H),1.69–1.64(m,1H),1.39(dd,J＝12.7,6.9Hz,2H)；13C核磁共振(126MHz,CDCl3)δ200.7,199.5,163.4,162.7,150.3,149.9,144.3,143.9,135.5,134.7,133.6,127.1,126.9,126.8,126.6,126.5,126.1,126.0,125.5,125.4,125.1,119.4,118.7,107.6,107.5,107.5,107.2,101.5,99.9,98.3,72.5,71.1,60.0,58.5,51.3,51.1,44.5,43.7,28.5,28.1,25.4,23.7.高分辨质谱分析(ESI):calcd.for C22H19NO3[M+H]+:346.1443,实际值:346.1446.
实施例25
原料：3-甲氧基苯酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C18H19NO2
精确分子量：281.1416
分子量：281.3550
结构式：
产率：53％
1H核磁共振(500MHz,CDCl3)δ7.15(t,J＝7.7Hz,1H),7.03(d,J＝7.4Hz,1H),6.63(t,J＝7.4Hz,1H),6.52(d,J＝8.1Hz,1H),6.44(d,J＝10.2Hz,1H),6.24(d,J＝10.2Hz,1H),5.69(s,1H),3.90(dd,J＝9.5,6.1Hz,1H),3.78(s,3H),3.58(d,J＝15.7Hz,1H),3.47(t,J＝8.1Hz,1H),3.25(q,J＝8.2Hz,1H),2.65(d,J＝15.8Hz,1H),2.05–1.95(m,1H),1.96–1.88(m,1H),1.84(dt,J＝12.7,6.5Hz,1H),1.47–1.34(m,1H)；13C核磁共振(126MHz,CDCl3)δ187.9,177.4,145.1,142.94129.,129.2,127.8,118.5,115.8,110.8,103.5,62.5,56.1,47.3,42.6,38.2,27.6,23.2.高分辨质谱分析(ESI):calcd.for C18H19NO2[M+H]+:282.1416,实际值:282.1413.
实施例26
原料：3,4-二甲氧基苯酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C19H21NO3
精确分子量：311.1521
分子量：311.3810
结构式：
产率：67％
1H核磁共振(500MHz,CDCl3)δ7.14(t,J＝7.7Hz,1H),7.05(d,J＝7.4Hz,1H),6.61(t,J＝7.3Hz,1H),6.53(d,J＝8.1Hz,1H),5.58(s,1H),4.92(s,1H),3.85(s,3H),3.72(dd,J＝9.6,5.5Hz,1H),3.50(s,3H),3.47(dd,J＝8.6,2.7Hz,1H),3.40(d,J＝15.6Hz,1H),3.20(dd,J＝16.3,8.6Hz,1H),2.66(d,J＝15.7Hz,1H),2.01–1.91(m,2H),1.90–1.85(m,1H),1.38(dd,J＝15.1,5.7Hz,1H)；13C核磁共振(126MHz,CDCl3)δ201.3,166.6,147.8,142.9,129.4,127.4,119.5,115.4,110.5,107.1,101.9,65.4,56.6,55.5,47.7,47.2,40.5,27.3,23.5.高分辨质谱分析(ESI):calcd.for C19H21NO3[M+H]+:312.1521实际值:312.1523.
实施例27
原料：3,5-二甲氧基苯酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C19H21NO3
精确分子量：311.1521
分子量：311.3810
结构式：
产率：58％
1H核磁共振(500MHz,CDCl3)δ7.09(t,J＝7.6Hz,1H),6.97(d,J＝7.4Hz,1H),6.60(t,J＝7.3Hz,1H),6.50(d,J＝8.0Hz,1H),5.63(s,1H),5.51(s,1H),4.03–3.91(m,1H),3.76(s,3H),3.60(d,J＝16.3Hz,2H),3.35(s,3H),3.12(dd,J＝15.7,7.8Hz,1H),2.74(d,J＝16.6Hz,1H),1.95–1.80(m,3H),1.46(td,J＝7.9,2.3Hz,1H)；13C核磁共振(126MHz,CDCl3)δ188.1,175.0,173.1,144.1,127.7,126.7,120.4,115.4,111.0,102.4,101.9,61.6,56.5,55.8,48.4,45.2,35.7,27.4,23.5.高分辨质谱分析(ESI):calcd.for C19H21NO3[M+H]+:312.1600,实际值:312.1602.
实施例28
原料：3-二乙胺基苯酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C21H26N2O
精确分子量：322.2045
分子量：322.4520
结构式：
产率：97％
1H核磁共振(500MHz,CDCl3)δ7.12(t,J＝7.6Hz,1H),7.03(d,J＝7.3Hz,1H),6.58(t,J＝7.3Hz,1H),6.50(d,J＝8.1Hz,1H),6.39(dd,J＝10.5,2.2Hz,1H),6.16(d,J＝10.5Hz,1H),5.33(d,J＝2.1Hz,1H),3.86(dd,J＝9.9,5.1Hz,1H),3.54–3.43(m,2H),3.37(q,J＝7.1Hz,4H),3.18(d,J＝7.5Hz,1H),2.62(d,J＝15.8Hz,1H),1.99–1.87(m,3H),1.34–1.28(m,1H),1.22(t,J＝7.1Hz,6H)；13C核磁共振(126MHz,CDCl3)δ197.4,156.5,143.9,143.2,129.1,127.3,119.9,118.5,114.9,110.1,96.6,64.4,47.2,45.7,44.9,39.7,27.8,23.5.高分辨质谱分析(ESI):calcd.for C21H26N2O[M+H]+:323.2045,实际值:323.2047.
实施例29
原料：3-吡咯烷基苯酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C21H24N2O
精确分子量：320.1889
分子量：320.4360
结构式：
产率：96％
1H核磁共振(500MHz,CDCl3)δ7.12(t,J＝7.7Hz,1H),7.02(d,J＝7.3Hz,1H),6.57(t,J＝7.3Hz,1H),6.49(d,J＝8.1Hz,1H),6.37(d,J＝10.3Hz,1H),6.14(d,J＝10.3Hz,1H),5.21(s,1H),3.87(dd,J＝9.9,5.0Hz,1H),3.54(s,2H),3.50–3.41(m,2H),3.32(s,2H),3.18(d,J＝8.0Hz,1H),2.60(d,J＝15.8Hz,1H),2.00(s,4H),1.95(dd,J＝10.7,5.4Hz,3H),1.35–1.28(m,1H)；13C核磁共振(126MHz,CDCl3)δ197.0,155.9,144.0,143.2,129.1,127.3,119.9,119.9,115.0,110.1,96.9,64.3,48.2,47.9,47.2,46.2,39.9,27.9,25.4,24.8,23.6.高分辨质谱分析(ESI):calcd.for C21H24N2O[M+H]+:321.1887,实际值:321.1891.
实施例30
原料：3-哌啶基苯酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C22H26N2O
精确分子量：334.2045
分子量：334.4630
结构式：
产率：87％
1H核磁共振(500MHz,CDCl3)δ7.12(t,J＝7.6Hz,1H),7.03(d,J＝7.3Hz,1H),6.59(d,J＝7.2Hz,1H),6.50(d,J＝8.0Hz,1H),6.46(d,J＝10.5Hz,1H),6.12(d,J＝10.5Hz,1H),5.45(s,1H),3.84(dd,J＝9.8,4.7Hz,1H),3.53–3.36(m,6H),3.18(d,J＝7.8Hz,1H),2.62(d,J＝15.8Hz,1H),2.00–1.85(m,3H),1.67(dd,J＝25.1,4.2Hz,6H),1.32(d,J＝10.2Hz,1H)；13C核磁共振(126MHz,CDCl3)δ198.3,157.9,143.3,143.2,129.2,127.3,119.8,118.8,115.0,110.2,98.5,64.4,48.1,47.2,45.9,39.7,27.8,25.6,24.4,23.5.高分辨质谱分析(ESI):calcd.for C22H26N2O[M+H]+:335.2123,实际值:335.2115.
实施例31
原料：1-萘酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C21H19NO
精确分子量：301.1467
分子量：301.3890
结构式：
产率：71％
1H核磁共振(500MHz,CDCl3)δ7.59(t,J＝7.4Hz,1H),7.38(t,J＝7.5Hz,1H),7.25(d,J＝3.2Hz,1H),7.16(t,J＝7.7Hz,1H),7.05(d,J＝7.3Hz,1H),6.67(d,J＝10.0Hz,1H),6.62(t,J＝7.3Hz,1H),6.55(d,J＝8.1Hz,1H),5.82(d,J＝10.0Hz,1H),3.85(dd,J＝9.8,5.7Hz,1H),3.51(t,J＝8.6Hz,1H),3.46(d,J＝15.5Hz,1H),3.21(dd,J＝16.7,8.6Hz,1H),2.73(d,J＝15.5Hz,1H),1.93(dt,J＝17.1,7.4Hz,2H),1.80(dt,J＝11.9,6.0Hz,1H),1.46–1.33(m,1H)；13C核磁共振(126MHz,CDCl3)δ201.9,143.0,138.3,134.6,133.2,129.4,128.0,127.6,127.6,126.7,126.4,119.2,115.4,110.4,65.2,47.7,47.2,39.7,27.6,23.6.高分辨质谱分析(ESI):calcd.for C21H19NO[M+H]+:302.1545,实际值:302.1543.
实施例32
原料：4-氯-1-萘酚、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C21H18ClNO
精确分子量：335.1077
分子量：335.8310
结构式：
产率：75％
1H核磁共振(500MHz,CDCl3)δ8.12(d,J＝7.5Hz,1H),7.81(d,J＝7.7Hz,1H),7.71(t,J＝7.5Hz,1H),7.50(t,J＝7.4Hz,1H),7.18(t,J＝7.5Hz,1H),7.06(d,J＝7.1Hz,1H),6.65(t,J＝7.1Hz,1H),6.57(d,J＝7.9Hz,1H),5.99(s,1H),3.90–3.74(m,1H),3.49(t,J＝10.9Hz,2H),3.26(q,J＝8.0Hz,1H),2.80(d,J＝15.6Hz,1H),2.03–1.95(m,1H),1.91(d,J＝8.8Hz,1H),1.85–1.77(m,1H),1.46–1.33(m,1H).13C核磁共振(126MHz,CDCl3)δ199.85,142.74,135.81,134.82,130.15,129.93,129.54,129.49,129.17,127.80,127.02,125.62,118.55,115.75,110.71,65.50,49.71,47.02,39.54,27.69,23.46.高分辨质谱分析(ESI):calcd.for C21H18ClNO[M+H]+:336.1150,实际值:336.1152.
实施例33
原料：1-萘酚、8-吡咯烷基-1-萘甲醛
反应条件：25℃/HFIP
产物：化学式：C21H19NO2
精确分子量：317.1416
分子量：351.4490
结构式：
产率：53％；dr＝1.5:1
1H核磁共振(500MHz,CDCl3)δ8.11(t,J＝9.2Hz,2H),7.64(d,J＝8.1Hz,2H),7.59(q,J＝6.8Hz,2H),7.43–7.35(m,3H),7.29(dd,J＝14.7,8.1Hz,10H),7.09(d,J＝6.7Hz,1H),6.92(d,J＝6.7Hz,1H),6.81(d,J＝9.8Hz,1H),6.74(t,J＝7.1Hz,2H),6.69(d,J＝9.8Hz,1H),6.55(d,J＝9.8Hz,1H),6.36(d,J＝9.8Hz,1H),4.52(d,J＝13.0Hz,1H),4.27(d,J＝9.4Hz,1H),3.62(d,J＝9.0Hz,1H),3.56(dd,J＝21.3,11.7Hz,4H),3.11(dd,J＝16.2,10.2Hz,2H),2.55–2.46(m,2H),2.24–2.09(m,2H),2.03–1.91(m,3H),1.81–1.72(m,1H),1.72–1.64(m,2H),1.49–1.42(m,1H),1.36(dd,J＝12.5,7.3Hz,2H)；13C核磁共振(126MHz,CDCl3)δ201.3,199.8,150.5,149.8,138.1,137.6,136.6,136.5,135.6,134.9,134.5,134.4,133.8,130.9,128.8,128.2,128.1,127.4,127.4,127.2,126.9,126.9,126.8,126.7,126.6,126.4,126.4,126.0,125.6,125.6,125.5,125.2,124.8,119.4,118.8,107.6,107.4,72.2,70.4,59.7,57.9,51.2,50.7,42.6,42.4,31.6,28.9,27.7,25.5,23.6,22.7,14.2.高分辨质谱分析(ESI):calcd.for C25H23NO[M+H]+:354.1780,实际值:354.1778.
实施例34
原料：2,3-二羟基萘、2-吡咯烷基苯甲醛
反应条件：25℃/HFIP
产物：化学式：C21H19NO2
精确分子量：317.1416
分子量：317.3880
结构式：
产率：78％；dr＝5:1
1H核磁共振(500MHz,CDCl3)δ7.33(dtd,J＝18.1,7.4,1.8Hz,3H),7.26–7.18(m,12H),7.15(t,J＝7.1Hz,4H),7.04(d,J＝7.6Hz,1H),7.02–6.96(m,4H),6.92(s,4H),6.81(s,1H),6.76(d,J＝8.0Hz,4H),6.72(dd,J＝14.4,7.1Hz,4H),6.69–6.65(m,1H),6.63(d,J＝8.1Hz,4H),6.43(s,4H),3.89(dd,J＝9.1,6.3Hz,1H),3.81(d,J＝16.8Hz,4H),3.67–3.61(m,1H),3.57(dd,J＝8.4,5.9Hz,4H),3.48–3.41(m,4H),3.41–3.32(m,2H),3.17(dd,J＝15.9,7.4Hz,4H),2.92(d,J＝16.8Hz,1H),2.83(d,J＝16.8Hz,4H),2.04–1.98(m,1H),1.87–1.79(m,2H),1.79–1.66(m,8H),1.52–1.43(m,4H),1.11–0.98(m,4H),0.88(t,J＝6.9Hz,1H)；13C核磁共振(126MHz,CDCl3)δ197.7,145.8,143.5,139.3,137.9,130.8,129.0,128.4,128.1,127.4,127.2,127.1,126.7,121.3,118.5,116.4,115.9,111.2,110.8,110.6,67.5,67.4,51.2,48.4,48.1,46.9,39.6,37.7,29.3,27.3,27.2,26.4,23.1,22.9.高分辨质谱分析(ESI):calcd.for C21H19NO2[M+H]+:318.1416,实际值:318.1419.
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 (8)

1.一种四氢喹啉螺环己二烯酮骨架化合物的合成方法，其特征在于：
由苯酚类或萘酚类化合物A与氨基甲醛类化合物B进行反应即得所述四氢喹啉螺环己二烯酮化合物，其反应在醇溶剂、甲苯和1,2-二氯乙烷一种或几种中进行。
2.根据权利要求1所述的合成方法，其特征在于：
所述四氢喹啉螺环己二烯酮骨架化合物为式Ⅰ、式Ⅱ、式Ⅲ和式Ⅳ所示化合物中任意一种：
其中
式Ⅰ、式Ⅱ、式Ⅲ、式Ⅳ中，虚线表示任选的单键；
n为1或2；
X选自碳和氮；
Y1、Y2独立地选自氢、氧、碳、甲氧基、二乙胺基、四氢吡咯、哌啶中任意一种；当Y1、Y2独立地选自氧、碳时，Y1、Y2构成环结构；
R1选自甲氧基、二乙胺基、四氢吡咯基、哌啶基中任意一种；并且
R2选自氢、氟、氯、溴、甲基、三氟甲基、硝基、甲氧基、氰基、对苯乙酰基、对甲氧基苯乙炔基、噻吩基、硼酸脂、丙烯酸甲酯中任意一种。
3.根据权利要求1或2所述的合成方法，其特征在于：
所述苯酚类或萘酚类化合物A为式Ⅴ所示化合物中任意一种；
所述氨基甲醛类化合物B为式Ⅵ、式Ⅶ所示化合物中任意一种：
其中
式Ⅴ、式Ⅵ、式Ⅶ中，虚线表示任选的单键；
n为1或2；
X选自碳和氮；
Y1、Y2独立地选自氢、氧、碳、甲氧基、二乙胺基、四氢吡咯基、哌啶基中任意一种；当Y1、Y2独立地选自氧、碳时，Y1、Y2构成环结构；
R1选自甲氧基、二乙胺基、四氢吡咯基、哌啶基中任意一种；并且
R2选自氢、氟、氯、溴、甲基、三氟甲基、硝基、甲基、甲氧基、氰基、对苯乙酰基、对甲氧基苯乙炔基、噻吩基、硼酸脂、丙烯酸甲酯中任意一种。
4.根据权利要求1-3任一项所述的合成方法，其特征在于：所述醇溶剂为三氟乙醇、六氟异丙醇、甲醇、异丙醇中任意一种。
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0℃-120℃条件下进行。
6.根据权利要求5所述的合成方法，其特征在于：所述化合物A与化合物B的摩尔比为1.1-1.5:1。
7.根据权利要求5或6任一项所述的合成方法，其特征在于：包括以下步骤：
将化合物A和化合物B加入到六氟异丙醇或六氟异丙醇与甲苯混合溶液中，搅拌反应，反应完毕进行浓缩、纯化，制得四氢喹啉螺环己二烯酮骨架化合物。
8.根据权利要求7所述的合成方法，其特征在于：所述六氟异丙醇与甲苯的混合溶液，两者体积比为1:1。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113461700A (zh) * 2021-03-31 2021-10-01 青岛农业大学 一种氧气促进的去芳香化反应在构建螺环二烯酮骨架中的应用

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113461700A (zh) * 2021-03-31 2021-10-01 青岛农业大学 一种氧气促进的去芳香化反应在构建螺环二烯酮骨架中的应用
CN113461700B (zh) * 2021-03-31 2022-05-13 青岛农业大学 一种氧气促进的去芳香化反应在构建螺环二烯酮骨架中的应用

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