CN115785096B - 高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法 - Google Patents

高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法 Download PDF

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CN115785096B
CN115785096B CN202211468031.0A CN202211468031A CN115785096B CN 115785096 B CN115785096 B CN 115785096B CN 202211468031 A CN202211468031 A CN 202211468031A CN 115785096 B CN115785096 B CN 115785096B
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CN115785096A (zh
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张新迎
梁淼淼
于彩云
徐园双
范学森
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Henan Normal University
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Abstract

本发明公开了一种高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法，属于有机合成技术领域。以邻烯基苯胺类化合物1和重氮吡唑啉酮类化合物2为原料，在钌或铱催化剂存在下，有机溶剂中升温反应，在含氧氛围或惰性气体氛围下，分别得到吡唑啉酮螺二氢喹啉类化合物3或吡唑啉酮螺吲哚啉类化合物4。本发明采用相同的原料，仅仅通过对反应条件的精准调控，即可高选择性地合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物，具有原料简单易得、操作简便、条件温和、选择性易控及底物适用范围广等优点，具有潜在的工业应用前景。

Description

高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化 合物的方法
技术领域
本发明属于有机合成技术领域，具体涉及高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法。
背景技术
螺杂环骨架通常具有较强的刚性和独特的三维立体结构，可为新药设计提供必要的特异空间，从而在现代药物开发中发挥着重要作用。其中，二氢喹啉螺环和吲哚啉螺环骨架广泛存在于具有显著抗肿瘤、抗菌、抗病毒和抗氧化活性的天然生物碱和人工合成化合物中，具有重要的药用价值。
因此，研究并开发从简单易得的原料出发，通过对反应条件的精准调控，高选择性地合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物，具有十分重要的理论意义和实用前景。
发明内容
本发明解决的技术问题是提供了一种高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法，该合成方法以邻烯基苯胺和重氮吡唑啉酮为原料，通过对反应条件的精准调控，高选择性地合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物，具有原料简单易得、操作简便、条件温和、选择性易控及底物适用范围广等优点，具有潜在的工业应用前景。
本发明为解决上述技术问题采用如下技术方案，一种高选择性合成吡唑啉酮螺二氢喹啉或吡唑啉酮螺吲哚啉类化合物的方法，包括如下操作：以邻烯基苯胺类化合物1和重氮吡唑啉酮类化合物2为原料，在钌或铱催化剂存在下，有机溶剂中升温反应，在含氧氛围或惰性气体氛围下，分别得到吡唑啉酮螺二氢喹啉类化合物3或吡唑啉酮螺吲哚啉类化合物4；反应方程式表示为：
其中：R1为氢、C1-4烷基、C1-4烷氧基、卤素、氰基或甲叉二氧基，R1为一元或多元取代，R2为氢、C1-4烷基、三氟甲基、苯基或取代苯基，R3为氢、C1-4烷基、苯基或取代苯基，R2和R3可以组合成1,3-丙二基或1,4-丁二基，R4为叔丁基、萘基、苯基或取代苯基，R5为C1-4烷基、C1-4烷氧基、C1-4烷氧酰基、苯基或取代苯基，以上所述取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基或卤素，苯环上的取代为一元或多元取代。
进一步地，在上述技术方案中，所述钌催化剂为二氯双(4-甲基异丙基苯基)钌(II)([Ru(p-cymene)Cl2]2)；铱催化剂为二氯(五甲基环戊二烯基)合铱(III)二聚体([IrCp*Cl2]2)。
进一步地，在上述技术方案中，所述有机溶剂为起到溶解原料的作用，优选1,4-二氧六环、四氢呋喃、1,2-二氯乙烷、二氯甲烷、乙腈、甲苯或甲醇。
进一步地，在上述技术方案中，所述含氧氛围为氧气或空气存在下。
进一步地，在上述技术方案中，所述惰性气体为氩气或氮气。
进一步地，在上述技术方案中，所述邻烯基苯胺类化合物1、重氮吡唑啉酮类化合物2与钌或铱催化剂摩尔比为1:1-1.5:0.025-0.05。其中，优选条件下，当生成产物3时，邻烯基苯胺类化合物1与重氮吡唑啉酮类化合物2摩尔比为1:1.5；当生成产物4时，邻烯基苯胺类化合物1与重氮吡唑啉酮类化合物2摩尔比为1:1.2。
进一步地，在上述技术方案中，所述反应温度为50-110℃；优选反应温度为80-100℃。
发明有益效果：
本发明与现有技术相比具有以下优点：(1)合成方法简单、高效，以邻烯基苯胺和重氮吡唑啉酮类化合物为原料，在钌(II)盐或铱(III)盐催化下，仅通过调控反应的气体氛围，即可高选择性、高产率地分别合成吡唑啉酮螺二氢喹啉和吡唑啉酮螺吲哚啉类化合物；(2)原料价廉易得；(3)反应条件温和，操作简便；(4)底物的适用范围广。
说明书附图
图1为实施例1中化合物3a的X-射线单晶衍射图。
图2为实施例3中化合物4o的X-射线单晶衍射图。
具体实施方式
以下通过实施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的实施例，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
向15mL反应瓶中，依次加入1a(26.6mg,0.2mmol)、2a(60.0mg,0.3mmol)、有机溶剂(2mL)和催化剂(0.01mmol)，盖上塞子密封，将其置于油浴中升温搅拌反应。待反应结束后，冷却至室温，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1)得黄色固体产物3a和/或白色固体产物4a。
通过改变反应的有机溶剂、催化剂、温度、时间、气体氛围以及底物的当量比，得到一系列的结果，见表1。
表1各种条件下化合物3a和4a的合成a
实施例2
向15mL反应瓶中，依次加入1a(26.6mg,0.2mmol)、2a(60.0mg,0.3mmol)、乙腈(2mL)和二氯双(4-甲基异丙基苯基)钌(II)([Ru(p-cymene)Cl2]2,6.2mg,0.01mmol)，盖上塞子密封，将其置于100℃油浴中搅拌反应5h。待反应结束后，冷却至室温，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1)得黄色固体产物3a(41.2mg,68％)。
向15mL反应瓶中，依次加入1a(26.6mg,0.2mmol)、2a(48.0mg,0.24mmol)、乙腈(2mL)和二氯双(4-甲基异丙基苯基)钌(II)([Ru(p-cymene)Cl2]2,6.2mg,0.01mmol)，盖上塞子密封，抽真空充氩气，置于100℃油浴中搅拌反应10h。待反应结束后，冷却至室温，抽滤，旋干，过硅胶柱分离(石油醚/乙酸乙酯＝10/1)得白色固体产物4a(48.8mg,80％)。
实施例3
依照实施例2的方法和步骤，通过改变反应物1和2，合成出系列吡唑啉酮螺二氢喹啉类化合物3或吡唑啉酮螺吲哚啉类化合物4，具体结果见表2和表3。
表2系列吡唑啉酮螺二氢喹啉类化合物3的合成a,b
表3各种吡唑啉酮螺吲哚啉类化合物4的合成a,b
代表性产物表征数据如下：
3,4'-Dimethyl-1-phenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3a)
1H NMR(400MHz,CDCl3):δ7.85(d,J＝8.0Hz,2H),7.33(t,J＝7.6Hz,2H),7.13(t,J＝7.2Hz,1H),7.09(d,J＝7.6Hz,1H),6.95(t,J＝7.6Hz,1H),6.66(t,J＝7.6Hz,1H),6.41(d,J＝7.6Hz,1H),4.94(s,1H),4.43(s,1H),2.11(s,3H),2.05(s,3H).13C{1H}NMR(100MHz,CDCl3):δ173.3,162.0,141.3,138.1,135.7,129.8,128.9,125.1,124.3,118.9,118.6,118.5,113.6,113.1,69.7,18.9,13.7.HRMS(ESI)m/z:[M+H]+Calcd for C19H18N3O304.1444；Found 304.1435.
3,4',6'-Trimethyl-1-phenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3b)
1H NMR(400MHz,CDCl3):δ7.88(d,J＝8.0Hz,2H),7.37(t,J＝7.2Hz,2H),7.16(t,J＝7.2Hz,1H),6.94(s,1H),6.84(d,J＝8.0Hz,1H),6.40(d,J＝8.0Hz,1H),4.99(s,1H),4.14(s,1H),2.23(s,3H),2.14(s,3H),2.07(d,J＝1.2Hz,3H).13C{1H}NMR(100MHz,CDCl3):δ173.3,161.9,138.8,138.1,135.8,130.2,128.9,127.8,125.1,124.9,119.2,118.6,113.8,113.0,69.5,20.7,19.0,13.8.HRMS(ESI)m/z:[M+H]+Calcd for C20H20N3O318.1601；Found 318.1598.
6'-Methoxy-3,4'-dimethyl-1-phenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3c)
1H NMR(600MHz,CDCl3):δ7.90(d,J＝7.8Hz,2H),7.39(t,J＝7.2Hz,2H),7.18(t,J＝7.2Hz,1H),6.76(d,J＝2.4Hz,1H),6.67(dd,J1＝8.4Hz,J2＝2.4Hz,1H),6.48(d,J＝9.0Hz,1H),5.09(s,1H),3.96(br s,1H),3.77(s,3H),2.18(s,3H),2.09(d,J＝1.2Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ173.3,162.3,152.9,137.1,135.9,135.0,131.8,120.3,120.0,117.9,114.9,114.5,113.8,110.8,69.6,55.9,19.0,13.8.HRMS(ESI)m/z:[M+H]+Calcd for C20H20N3O2334.1550；Found 334.1539.
3,4'-Dimethyl-5-oxo-1-phenyl-1,5-dihydro-1'H-spiro[pyrazole-4,2'-quinoline]-6'-carbonitrile(3e)
1H NMR(400MHz,CDCl3):δ7.79(d,J＝8.0Hz,2H),7.34(t,J＝8.0Hz,2H),7.30(s,1H),7.19-7.15(m,2H),6.44(d,J＝8.4Hz,1H),5.23(s,1H),5.06(s,1H),2.15(s,3H),2.06(s,3H).13C{1H}NMR(150MHz,CDCl3):δ172.3,161.1,145.1,137.6,134.3,133.7,129.0,128.3,125.5,119.9,118.9,118.7,114.9,113.1,100.5,69.7,18.7,13.7.HRMS(ESI)m/z:[M+H]+Calcd for C20H17N4O 329.1397；Found 329.1387
7'-(tert-Butyl)-3,4'-dimethyl-1-phenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3f)
1H NMR(400MHz,CDCl3):δ7.91(d,J＝7.6Hz,2H),7.39(t,J＝7.2Hz,2H),7.17(t,J＝7.6Hz,1H),7.07(d,J＝8.0Hz,1H),6.75(dd,J1＝8.0Hz,J2＝2.0Hz,1H),6.52(d,J＝2.0Hz,1H),4.95(s,1H),4.14(br s,1H),2.20(s,3H),2.08(d,J＝1.2Hz,3H),1.26(s,9H).13C{1H}NMR(100MHz,CDCl3):δ173.2,162.0,153.3,140.7,138.1,135.6,128.9,125.1,124.1,118.7,116.6,115.9,112.6,110.2,69.8,34.6,31.2,18.9,13.9.HRMS(ESI)m/z:[M+H]+Calcd for C23H26N3O 360.2070；Found 360.2061.
7'-Fluoro-3,4'-dimethyl-1-phenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3h)
1H NMR(600MHz,CDCl3):δ7.80(d,J＝7.8Hz,2H),7.32(t,J＝7.2Hz,2H),7.14(t,J＝7.2Hz,1H),7.03(dd,J1＝7.8Hz,J2＝6.0Hz,1H),6.33(td,J1＝8.4Hz,J2＝2.4Hz,1H),6.16(dd,J1＝10.2Hz,J2＝2.4Hz,1H),4.92(s,1H),4.73(s,1H),2.13(s,3H),2.05(d,J＝1.2Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ173.1,163.9(d,1JC-F＝244.1Hz),161.8,143.0(d,3JC-F＝12.3Hz),137.9,135.2,128.9,125.8(d,3JC-F＝9.2Hz),125.2,118.7,115.2(d,5JC-F＝2.0Hz),112.5(d,4JC-F＝2.6Hz),105.0(d,2JC-F＝21.8Hz),100.1(d,2JC-F＝26.9Hz),69.7,19.0,13.7.19F NMR(565MHz,CDCl3):δ-111.85–-111.89(m).HRMS(ESI)m/z:[M+H]+Calcd for C19H17FN3O 322.1350；Found 322.1339.
3,8'-Dimethyl-1-phenyl-5'H-spiro[pyrazole-4,6'-[1,3]dioxolo[4,5-g]quinolin]-5(1H)-one(3j)
1H NMR(600MHz,CDCl3):δ7.83(d,J＝8.4Hz,2H),7.34(t,J＝7.8Hz,2H),7.14(t,J＝7.2Hz,1H),6.64(s,1H),6.10(s,1H),5.83(d,J＝6.6Hz,2H),4.88(s,1H),4.34(s,1H),2.15(s,3H),2.02(s,3H).13C{1H}NMR(150MHz,CDCl3):δ173.6,162.0,148.4,140.5,138.0,137.1,135.6,128.9,125.1,118.7,112.1,111.3,104.5,100.8,95.7,69.6,19.3,13.8.HRMS(ESI)m/z:[M+H]+Calcd for C20H18N3O3348.1343；Found 348.1325.
3-Methyl-1,4'-diphenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3n)
1H NMR(400MHz,CDCl3):δ7.87(d,J＝7.6Hz,2H),7.38-7.32(m,7H),7.15(t,J＝7.2Hz,1H),7.00(td,J1＝7.6Hz,J2＝1.2Hz,1H),6.91(d,J＝7.2Hz,1H),6.60(td,J1＝7.6Hz,J2＝0.8Hz,1H),6.54(d,J＝8.0Hz,1H),5.12(d,J＝2.0Hz,1H),4.48(s,1H),2.20(s,3H).13C{1H}NMR(100MHz,CDCl3):δ173.1,161.6,142.3,141.7,138.0,137.9,130.0,129.0,128.8,128.4,128.2,126.8,125.2,118.7,118.6,115.3,113.6,69.6,13.9.HRMS(ESI)m/z:[M+H]+Calcd for C24H20N3O 366.1601；Found 366.1597.
3,8'-Dimethyl-1,4'-diphenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3p)
1H NMR(400MHz,CDCl3):δ7.90(d,J＝7.6Hz,2H),7.39-7.32(m,7H),7.16(t,J＝7.6Hz,1H),6.95(d,J＝7.2Hz,1H),6.80(d,J＝7.6Hz,1H),6.56(t,J＝7.6Hz,1H),5.14(d,J＝1.2Hz,1H),4.26(s,1H),2.23(s,3H),2.14(s,3H).13C{1H}NMR(150MHz,CDCl3):δ173.5,161.6,142.6,139.5,138.4,138.0,131.5,128.93,128.88,128.3,128.1,125.2,125.0,120.7,118.7,118.3,118.0,114.8,69.7,17.0,13.8.HRMS(ESI)m/z:[M+H]+Calcd forC25H22N3O 380.1757；Found 380.1763.
3-Methyl-1,3'-diphenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3r)
1H NMR(600MHz,CDCl3):δ7.78(d,J＝7.8Hz,2H),7.37(t,J＝7.2Hz,2H),7.25-7.23(m,3H),7.19-7.17(m,3H),7.06(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.03(d,J＝7.8Hz,1H),6.77(s,1H),6.73(td,J1＝7.8Hz,J2＝1.2Hz,1H),6.54(d,J＝7.8Hz,1H),4.20(s,1H),2.14(s,3H).13C{1H}NMR(150MHz,CDCl3):δ172.3,161.3,140.0,137.7,137.0,129.9,129.2,128.94,128.87,128.7,128.4,128.0,126.8,125.4,119.4,119.2,119.0,112.9,71.1,14.1.HRMS(ESI)m/z:[M+H]+Calcd for C24H20N3O 366.1601；Found 366.1600.
3'-Methyl-1'-phenyl-7,8,9,10-tetrahydro-5H-spiro[phenanthridine-6,4'-pyrazol]-5'(1'H)-one(3t)
1H NMR(400MHz,CDCl3):δ7.92(d,J＝7.6Hz,2H),7.39(t,J＝7.6Hz,2H),7.18(t,J＝7.6Hz,1H),7.11(d,J＝7.6Hz,1H),6.99(td,J1＝7.6Hz,J2＝1.2Hz,1H),6.71(td,J1＝7.6Hz,J2＝1.2Hz,1H),6.47(dd,J1＝7.6Hz,J2＝0.8Hz,1H),4.16(s,1H),2.49-2.46(m,2H),2.11(s,3H),1.94-1.87(m,1H),1.79-1.67(m,4H),1.61-1.52(m,1H).13C{1H}NMR(100MHz,CDCl3):δ173.3,161.0,139.9,137.9,130.7,129.0,128.6,125.2,122.8,122.2,120.3,118.8,118.7,112.8,72.0,25.1,24.3,22.2,22.1,13.8.HRMS(ESI)m/z:[M+H]+Calcd for C22H22N3O344.1757；Found 344.1754.
1-(4-Fluorophenyl)-3,4'-dimethyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3w)
1H NMR(400MHz,CDCl3):δ7.86-7.83(m,2H),7.13(d,J＝7.6Hz,1H),7.07-7.00(m,3H),6.71(t,J＝7.6Hz,1H),6.47(d,J＝7.6Hz,1H),5.00(s,1H),4.30(s,1H),2.17(s,3H),2.09(s,3H).13C{1H}NMR(150MHz,CDCl3):δ173.1,162.0,159.8(d,1JC-F＝242.6Hz),141.1,135.9,134.2(d,4JC-F＝3.2Hz),129.8,124.4,120.3(d,3JC-F＝7.4Hz),119.0,118.7,115.6(d,2JC-F＝21.8Hz),113.4,113.0,69.6,18.9,13.7.19F NMR(565MHz,CDCl3):δ-116.98–-117.02(m).HRMS(ESI)m/z:[M+H]+Calcd for C19H17FN3O 322.1350；Found 322.1340.
3,4'-Dimethyl-1-(m-tolyl)-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3z)
1H NMR(600MHz,CDCl3):δ7.70(s,1H),7.69(d,J＝8.4Hz,1H),7.25(t,J＝7.8Hz,1H),7.12(d,J＝7.8Hz,1H),7.02(td,J1＝7.8Hz,J2＝1.2Hz,1H),6.99(d,J＝7.2Hz,1H),6.70(td,J1＝7.8Hz,J2＝1.2Hz,1H),6.48(dd,J1＝7.8Hz,J2＝1.2Hz,1H),4.99(s,1H),4.25(s,1H),2.36(s,3H),2.16(s,3H),2.08(d,J＝1.2Hz,3H).13C{1H}NMR(100MHz,CDCl3):δ173.2,161.8,141.2,138.8,137.9,135.7,129.7,128.7,125.9,124.3,119.3,119.1,118.7,115.9,113.6,113.0,69.6,21.6,18.9,13.7.HRMS(ESI)m/z:[M+H]+Calcd forC20H20N3O 318.1601；Found318.1593.
1-(2,6-Dimethylphenyl)-3,4'-dimethyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3ee)
1H NMR(600MHz,CDCl3):δ7.19(t,J＝7.2Hz,1H),7.13-7.09(m,3H),7.04(td,J1＝7.8Hz,J2＝1.8Hz,1H),6.70(td,J1＝7.8Hz,J2＝1.2Hz,1H),6.52(dd,J1＝7.8Hz,J2＝0.6Hz,1H),5.05(s,1H),4.19(s,1H),2.25(s,3H),2.20(s,3H),2.13(s,3H),2.11(d,J＝1.2Hz,3H).13C{1H}NMR(100MHz,CDCl3):δ174.0,161.8,141.1,136.6,135.8,134.2,129.7,129.2,128.6,128.4,124.4,119.2,118.7,113.6,113.1,68.3,19.0,18.3,18.2,13.8.HRMS(ESI)m/z:[M+H]+Calcd for C21H22N3O 332.1757；Found 332.1744.
1-(tert-Butyl)-3,4'-dimethyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3gg)
1H NMR(600MHz,CDCl3):δ7.09(dd,J1＝7.2Hz,J2＝0.6Hz,1H),7.01(td,J1＝7.2Hz,J2＝1.2Hz,1H),6.67(td,J1＝7.2Hz,J2＝0.6Hz,1H),6.48(dd,J1＝7.8Hz,J2＝0.6Hz,1H),4.90(s,1H),4.01(br s,1H),2.06(d,J＝1.8Hz,3H),2.04(s,3H),1.49(s,9H).13C{1H}NMR(150MHz,CDCl3):δ175.5,159.7,141.5,134.9,129.5,124.2,119.3,118.4,114.5,112.8,69.4,57.5,28.1,18.9,13.7.HRMS(ESI)m/z:[M+H]+Calcd for C17H22N3O284.1757；Found 284.1754.3-Ethyl-4'-methyl-1-phenyl-1'H-spiro[pyrazole-4,2'-quinolin]-5(1H)-one(3hh)
1H NMR(600MHz,CDCl3):δ7.91(d,J＝8.4Hz,2H),7.37(t,J＝7.8Hz,2H),7.16(t,J＝7.8Hz,1H),7.11(d,J＝7.8Hz,1H),7.00(t,J＝7.2Hz,1H),6.69(t,J＝7.8Hz,1H),6.45(d,J＝7.8Hz,1H),5.00(s,1H),4.24(d,J＝10.8Hz,1H),2.59-2.55(m,2H),2.07(s,3H),1.25(t,J＝7.2Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ173.5,165.7,141.2,138.2,135.3,129.7,128.9,125.0,124.3,119.0,118.65,118.59,114.0,113.0,69.8,21.5,18.9,9.7.HRMS(ESI)m/z:[M+H]+Calcd for C20H20N3O 318.1601；Found 318.1602.
Ethyl 4'-methyl-5-oxo-1-phenyl-1,5-dihydro-1'H-spiro[pyrazole-4,2'-quinoline]-3-carboxylate(3kk)
1H NMR(600MHz,CDCl3):δ7.89(d,J＝7.8Hz,2H),7.39(t,J＝7.8Hz,2H),7.24(t,J＝7.8Hz,1H),7.12(d,J＝7.8Hz,1H),7.03(td,J1＝7.2Hz,J2＝1.2Hz,1H),6.70(t,J＝7.2Hz,1H),6.47(d,J＝7.2Hz,1H),5.01(s,1H),4.46(s,1H),4.15-4.03(m,2H),2.08(d,J＝1.8Hz,3H),0.91(t,J＝7.2Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ174.3,159.2,150.0,141.1,137.3,136.0,129.7,129.1,126.3,124.1,119.3,119.2,118.6,113.0,111.7,68.3,62.0,19.0,13.4.HRMS(ESI)m/z:[M+H]+Calcd for C21H20N3O3362.1499；Found 362.1488.
3,3,3'-Trimethyl-1'-phenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4a)
1H NMR(400MHz,CDCl3):δ7.85(d,J＝8.4Hz,2H),7.35(t,J＝8.0Hz,2H),7.15(t,J＝7.6Hz,1H),7.07(t,J＝7.2Hz,1H),7.00(d,J＝7.2Hz,1H),6.83(t,J＝7.2Hz,1H),6.68(d,J＝8.0Hz,1H),4.37(s,1H),1.96(s,3H),1.37(s,3H),1.33(s,3H).13C{1H}NMR(100MHz,CDCl3):δ172.7,162.2,147.5,138.0,136.3,128.9,128.2,125.0,121.9,120.5,118.6,110.7,79.6,50.5,26.0,23.3,15.7.HRMS(ESI)m/z:[M+H]+Calcd for C19H20N3O 306.1601；Found 306.1593.
5-Methoxy-3,3,3'-trimethyl-1'-phenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4c)
1H NMR(600MHz,CDCl3):δ7.87(d,J＝7.8Hz,2H),7.38(t,J＝7.8Hz,2H),7.17(t,J＝7.8Hz,1H),6.68-6.62(m,3H),4.06(s,1H),3.77(s,3H),1.97(s,3H),1.37(s,3H),1.32(s,3H).13C{1H}NMR(150MHz,CDCl3):δ172.5,162.4,155.0,140.8,138.5,138.0,128.9,125.0,118.7,112.6,111.8,109.1,79.7,55.9,50.6,25.9,22.9,15.7.HRMS(ESI)m/z:[M+H]+Calcd for C20H22N3O2336.1707；Found 336.1703.
5-Bromo-3,3,3'-trimethyl-1'-phenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4e)
1H NMR(600MHz,CDCl3):δ7.82(d,J＝7.8Hz,2H),7.36(t,J＝7.8Hz,2H),7.18-7.16(m,2H),7.09(d,J＝2.4Hz,1H),6.56(d,J＝8.4Hz,1H),4.40(s,1H),2.00(s,3H),1.36(s,3H),1.32(s,3H).13C{1H}NMR(150MHz,CDCl3):δ172.3,161.6,146.7,138.6,137.8,131.0,128.9,125.22,125.15,118.6,112.3,112.0,79.7,50.5,25.6,23.5,15.8.HRMS(ESI)m/z:[M+H]+Calcd for C19H19BrN3O 384.0706；Found 384.0702.
6-(tert-Butyl)-3,3,3'-trimethyl-1'-phenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4g)
1H NMR(400MHz,CDCl3):δ7.89(d,J＝8.0Hz,2H),7.38(t,J＝7.6Hz,2H),7.17(t,J＝7.2Hz,1H),6.92(d,J＝7.6Hz,1H),6.88(dd,J1＝7.6Hz,J2＝1.6Hz,1H),6.78(d,J＝1.2Hz,1H),4.14(s,1H),2.01(s,3H),1.38(s,3H),1.34(s,3H),1.29(s,9H).13C{1H}NMR(100MHz,CDCl3):δ172.8,162.4,151.8,147.5,138.1,133.5,128.9,125.0,121.3,118.7,117.7,108.2,79.6,50.4,34.8,31.5,26.0,23.7,15.8.HRMS(ESI)m/z:[M+H]+Calcd forC23H28N3O 362.2227；Found 362.2229.
6-Fluoro-3,3,3'-trimethyl-1'-phenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4i)
1H NMR(600MHz,CDCl3):δ7.85(d,J＝7.8Hz,2H),7.39(t,J＝7.8Hz,2H),7.18(t,J＝7.2Hz,1H),6.91(dd,J1＝7.8Hz,J2＝5.4Hz,1H),6.52(t,J＝7.8Hz,1H),6.43(d,J＝9.0Hz,1H),4.31(s,1H),2.03(s,3H),1.37(s,3H),1.33(s,3H).13C{1H}NMR(150MHz,CDCl3):δ172.3,163.3(d,1JC-F＝240.6Hz),161.6,148.9(d,3JC-F＝10.7Hz),137.9,131.7(d,4JC-F＝2.6Hz),128.9,125.2,122.5(d,3JC-F＝9.5Hz),118.7,106.7(d,2JC-F＝22.5Hz),98.5(d,2JC-F＝27.5Hz),79.8,49.9,25.8,23.8,15.8.19F NMR(565MHz,CDCl3):δ-114.45–-114.49(m).HRMS(ESI)m/z:[M+H]+Calcd for C19H19FN3O 324.1507；Found 324.1503.
3,3,3',5,7-Pentamethyl-1'-phenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4l)
1H NMR(400MHz,CDCl3):δ7.89(d,J＝7.6Hz,2H),7.39(t,J＝7.2Hz,2H),7.18(t,J＝7.6Hz,1H),6.76(s,1H),6.68(s,1H),3.88(s,1H),2.27(s,3H),2.15(s,3H),1.95(s,3H),1.37(s,3H),1.32(s,3H).13C{1H}NMR(100MHz,CDCl3):δ172.7,162.5,143.4,138.1,136.5,130.5,129.9,128.9,125.0,120.3,120.1,118.7,79.5,50.7,26.2,23.0,21.0,16.6,15.6.HRMS(ESI)m/z:[M+H]+Calcd for C21H24N3O 334.1914；Found 334.1910.
3,3'-Dimethyl-1',3-diphenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4n)
1H NMR(600MHz,CDCl3):δ7.81(d,J＝7.8Hz,2H),7.37(t,J＝7.2Hz,2H),7.26-7.20(m,6H),7.16(t,J＝7.8Hz,1H),7.08(d,J＝7.8Hz,1H),6.92(td,J1＝7.2Hz,J2＝0.6Hz,1H),6.82(d,J＝7.8Hz,1H),4.32(s,1H),1.85(s,3H),1.27(s,3H).13C{1H}NMR(150MHz,CDCl3):δ173.3,162.6,149.1,141.7,137.9,133.7,128.9,128.7,128.5,127.7,127.3,125.1,124.9,120.7,118.7,110.9,80.0,58.7,24.4,14.7.HRMS(ESI)m/z:[M+H]+Calcd for C24H22N3O 368.1757；Found 368.1760.
3,3',7-Trimethyl-1',3-diphenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4q)
1H NMR(600MHz,CDCl3):δ7.82(d,J＝8.4Hz,2H),7.38(t,J＝7.8Hz,2H),7.27-7.23(m,5H),7.18(t,J＝7.2Hz,1H),7.04(d,J＝7.2Hz,1H),6.95(d,J＝7.8Hz,1H),6.87(t,J＝7.2Hz,1H),4.11(s,1H),2.23(s,3H),1.85(s,3H),1.30(s,3H).13C{1H}NMR(150MHz,CDCl3):δ173.3,162.8,147.6,141.8,137.9,133.2,129.6,128.9,128.5,127.7,127.3,125.1,122.4,120.9,120.4,118.8,79.8,59.2,24.8,16.8,14.6.HRMS(ESI)m/z:[M+H]+Calcd for C25H24N3O382.1914；Found 382.1909
3”-Methyl-1”-phenyldispiro[cyclopentane-1,3'-indoline-2',4”-pyrazol]-5”(1”H)-one(4r)
1H NMR(400MHz,DMSO-d6):δ7.82(d,J＝7.6Hz,2H),7.45(t,J＝7.6Hz,2H),7.20(t,J＝7.6Hz,1H),7.04-7.00(m,2H),6.70(td,J1＝7.6Hz,J2＝0.8Hz,1H),6.63(d,J＝7.2Hz,1H),6.47(s,1H),2.71-2.66(m,1H),2.04-2.00(m,1H),1.84(s,3H),1.78-1.68(m,2H),1.57-1.54(m,2H),1.40-1.35(m,2H).13C{1H}NMR(100MHz,DMSO-d6):δ172.9,162.9,149.2,138.3,136.7,129.5,128.3,125.2,122.4,119.4,118.5,109.4,78.6,60.3,36.7,34.2,25.3,24.7,15.5.HRMS(ESI)m/z:[M+H]+Calcd for C21H22N3O 332.1757；Found332.1756.
1'-(4-Fluorophenyl)-3,3,3'-trimethylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4u)
1H NMR(600MHz,CDCl3):δ7.81(dd,J1＝9.6Hz,J2＝5.4Hz,2H),7.09(t,J＝7.2Hz,1H),7.05-7.00(m,3H),6.85(t,J＝7.2Hz,1H),6.70(d,J＝7.8Hz,1H),4.38(s,1H),1.98(s,3H),1.37(s,3H),1.34(s,3H).13C{1H}NMR(150MHz,CDCl3):δ172.6,162.4,159.8(d,1JC-F＝242.9Hz),147.4,136.2,134.2(d,4JC-F＝1.5Hz),128.3,121.9,120.6,120.3(d,3JC-F＝8.1Hz),115.5(d,2JC-F＝21.9Hz),110.7,79.6,50.5,26.0,23.2,15.7.19F NMR(565MHz,CDCl3):δ-117.19–-117.24(m).HRMS(ESI)m/z:[M+H]+Calcd for C19H19FN3O 324.1507；Found 324.1502.
1'-(4-Iodophenyl)-3,3,3'-trimethylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4x)
1H NMR(600MHz,CDCl3):δ7.65(s,4H),7.09(t,J＝7.8Hz,1H),7.01(d,J＝7.2Hz,1H),6.86(t,J＝7.8Hz,1H),6.70(d,J＝7.8Hz,1H),3.55(br s,1H),1.99(s,3H),1.36(s,3H),1.33(s,3H).13C{1H}NMR(100MHz,CDCl3):δ172.8,162.6,147.3,137.8,137.7,136.1,128.3,122.0,120.7,120.2,110.7,88.6,79.6,50.6,25.8,23.4,15.7.HRMS(ESI)m/z:[M+H]+Calcd for C19H19IN3O 432.0567；Found 432.0565.
1'-(3-Chlorophenyl)-3,3,3'-trimethylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4aa)
1H NMR(400MHz,CDCl3):δ7.89(t,J＝2.0Hz,1H),7.78-7.75(m,1H),7.25(t,J＝8.0Hz,1H),7.13-7.07(m,2H),7.00(d,J＝7.2Hz,1H),6.85(t,J＝7.2Hz,1H),6.70(d,J＝7.6Hz,1H),4.41(s,1H),2.00(s,3H),1.36(s,3H),1.33(s,3H).13C{1H}NMR(100MHz,CDCl3):δ173.0,162.7,147.4,138.9,136.0,134.6,129.9,128.3,124.8,121.9,120.6,118.4,116.2,110.7,79.8,50.7,25.7,23.5,15.7.HRMS(ESI)m/z:[M+H]+Calcd forC19H19ClN3O 340.1211；Found 340.1203.
3,3,3'-Trimethyl-1'-(o-tolyl)spiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4cc)
1H NMR(600MHz,CDCl3):δ7.32-7.31(m,1H),7.28-7.24(m,3H),7.10(td,J1＝7.8Hz,J2＝1.2Hz,1H),7.04(d,J＝7.2Hz,1H),6.86(t,J＝7.2Hz,1H),6.74(d,J＝7.8Hz,1H),4.20(s,1H),2.31(s,3H),1.92(s,3H),1.43(s,3H),1.42(s,3H).13C{1H}NMR(100MHz,CDCl3):δ173.2,162.2,147.3,136.7,136.1,134.4,131.1,128.3,128.2,126.6,125.5,122.0,120.7,110.9,78.5,50.0,26.9,22.2,18.9,15.6.HRMS(ESI)m/z:[M+H]+Calcd forC20H22N3O 320.1757；Found 320.1751.
1'-(3,4-Dimethylphenyl)-3,3,3'-trimethylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4ee)
1H NMR(400MHz,CDCl3):δ7.64(s,1H),7.57(dd,J1＝8.4Hz,J2＝2.4Hz,1H),7.12(d,J＝8.0Hz,1H),7.09(td,J1＝7.6Hz,J2＝1.2Hz,1H),7.00(d,J＝6.8Hz,1H),6.84(td,J1＝7.6Hz,J2＝0.8Hz,1H),6.72(d,J＝7.6Hz,1H),4.22(s,1H),2.27(s,3H),2.24(s,3H),1.98(s,3H),1.38(s,3H),1.34(s,3H).13C{1H}NMR(100MHz,CDCl3):δ172.4,161.9,147.5,137.2,136.4,135.8,133.5,129.9,128.2,121.9,120.6,119.9,116.3,110.7,79.4,50.4,25.9,23.4,20.0,19.3,15.7.HRMS(ESI)m/z:[M+H]+Calcd for C21H24N3O 334.1914；Found334.1910.
3'-Ethyl-3,3-dimethyl-1'-phenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4gg)
1H NMR(400MHz,CDCl3):δ7.88(d,J＝7.6Hz,2H),7.36(t,J＝7.2Hz,2H),7.15(t,J＝7.2Hz,1H),7.08(td,J1＝7.6Hz,J2＝0.8Hz,1H),6.99(d,J＝7.2Hz,1H),6.84(td,J1＝7.6Hz,J2＝0.8Hz,1H),6.69(d,J＝7.6Hz,1H),4.31(s,1H),2.36-2.30(m,1H),2.23-2.17(m,1H),1.37(s,3H),1.31(s,3H),1.19(t,J＝7.2Hz,3H).13C{1H}NMR(100MHz,CDCl3):δ173.0,166.0,147.7,138.2,136.4,128.8,128.2,124.9,121.9,120.5,118.6,110.6,79.7,50.6,26.4,22.9,22.8,9.4.HRMS(ESI)m/z:[M+H]+Calcd for C20H22N3O 320.1757；Found320.1751.
5-Bromo-3'-isopropyl-3,3-dimethyl-1'-phenylspiro[indoline-2,4'-pyrazol]-5'(1'H)-one(4ii)1H NMR(600MHz,CDCl3):δ7.82(d,J＝7.8Hz,2H),7.34(t,J＝9.0Hz,2H),7.18(dd,J1＝8.4Hz,J2＝1.8Hz,1H),7.15(t,J＝7.8Hz,1H),7.08(d,J＝1.8Hz,1H),6.55(d,J＝8.4Hz,1H),4.39(br s,1H),2.54-2.50(m,1H),1.35(s,3H),1.30(s,3H),1.27(d,J＝6.6Hz,3H),1.20(d,J＝6.6Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ172.7,168.9,146.9,138.7,137.9,130.9,128.8,125.2,125.0,118.5,112.1,111.8,80.2,51.3,29.6,25.8,23.8,23.5,18.8.HRMS(ESI)m/z:[M+H]+Calcd for C21H23BrN3O 412.1019；Found412.1024.
实施例4
本发明所合成的产物吡唑啉酮螺二氢喹啉类化合物3或吡唑啉酮螺吲哚啉类化合物4可进行一系列反应，从而合成进一步的衍生物。例如：
在25mL两颈瓶中，依次加入3a(60.7mg,0.2mmol)和Pd/C(10wt％,10mg)，之后加入甲醇将其溶解，抽真空，充氢气，室温下反应24小时。待反应结束后，过滤、浓缩，过硅胶柱分离(石油醚/乙酸乙酯＝10/1)得到白色固体产物5(53.7mg,88％)。该化合物的表征数据如下：1H NMR(400MHz,CDCl3):δ7.91(d,J＝7.8Hz,2H),7.40(t,J＝7.8Hz,2H),7.21-7.18(m,2H),7.07(t,J＝7.8Hz,1H)6.81(t,J＝7.8Hz,1H),6.62(d,J＝7.8Hz,1H),4.02(s,1H),3.07-3.03(m,1H),2.19(s,3H),2.03(dd,J1＝13.2Hz,J2＝4.8Hz,1H),1.97(d,J＝12.6Hz,1H),1.43(d,J＝7.2Hz,3H).13C{1H}NMR(150MHz,CDCl3):δ173.9,164.0,141.2,138.0,128.9,127.5,126.0,125.2,125.1,118.9,118.7,114.8,65.6,37.9,27.1,19.3,15.3.HRMS(ESI)m/z:[M+H]+Calcd for C19H20N3O 306.1601；Found 306.1595.
向15mL反应管中，依次加入3d(38.2mg,0.1mmol)、3,6-二氢-2H-吡喃-4-硼酸频哪醇酯(23.1mg,0.11mmol)、磷酸钾(25.5mg,0.112mmol)、四(三苯基膦)钯(5.8mg,0.005mmol)和无水甲醇(1mL)。抽真空充氩气，将反应体系置于80℃油浴中反应14小时。反应结束后，将反应体系冷却至室温，用硅藻土过滤，滤液旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1)得到黄色固体产物6(23.9mg,62％)。该化合物的表征数据如下：1H NMR(600MHz,CDCl3):δ7.86(d,J＝8.4Hz,2H),7.35(t,J＝7.8Hz,2H),7.17-7.15(m,2H),7.04(dd,J1＝7.8Hz,J2＝1.2Hz,1H),6.44(d,J＝8.4Hz,1H),5.96(s,1H),5.02(s,1H),4.48(s,1H),4.300-4.296(m,2H),3.91(t,J＝5.4Hz,2H),2.457-2.455(m,2H),2.16(s,3H),2.11(s,3H).13C{1H}NMR(150MHz,CDCl3):δ173.1,161.8,140.6,138.0,135.7,133.7,130.9,128.9,126.1,125.1,120.6,119.6,118.8,118.6,114.0,112.9,69.6,65.9,64.6,27.3,19.0,13.8.HRMS(ESI)m/z:[M+H]+Calcd for C24H24N3O2386.1863；Found 386.1860.
在25mL两颈瓶中，加入4a(61.1mg,0.2mmol)，抽真空充氩气，之后加入干燥二氯甲烷(2mL)将其溶解。随后将反应瓶置于冰水浴中，缓慢滴加二异丁基氢化铝(1M甲苯溶液,0.67mL,1.0mmol)，滴加完毕后于0℃下反应3小时。然后，加饱和氯化铵溶液淬灭反应，用乙醚萃取。有机相水洗、干燥、过滤、浓缩，过硅胶柱分离(石油醚/乙酸乙酯＝10/1)得到白色固体产物7(18.6mg,32％)。该化合物的表征数据如下：1H NMR(600MHz,CDCl3):δ7.28-7.24(m,2H),7.06-7.03(m,4H),6.85-6.81(m,2H),6.62-6.61(m,1H),4.12(br s,1H),3.92(d,J＝9.6Hz,1H),3.74(d,J＝9.6Hz,1H),1.73(s,3H),1.30(s,3H),1.27(s,3H).13C{1H}NMR(150MHz,CDCl3):δ152.3,147.5,146.2,137.1,129.2,127.9,121.8,120.0,119.4,113.1,108.9,83.5,54.1,44.9,27.1,20.6,13.9.HRMS(ESI)m/z:[M+H]+Calcd forC19H22N3292.1808；Found 292.1804.
向15mL反应管中，依次加入4e(38.4mg,0.1mmol)、3,6-二氢-2H-吡喃-4-硼酸频哪醇酯(23.1mg,0.11mmol)、磷酸钾(25.5mg,0.112mmol)、四(三苯基膦)钯(5.8mg,0.005mmol)和无水甲醇(2mL)。抽真空充氩气，将反应体系置于80℃油浴中反应14小时。反应结束后，将反应体系冷却至室温，用硅藻土过滤，滤液旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1)得到黄色固体产物8(31.4mg,81％)。该化合物的表征数据如下：1H NMR(600MHz,CDCl3):δ7.86(d,J＝7.8Hz,2H),7.37(t,J＝7.8Hz,2H),7.17(t,J＝7.2Hz,1H),7.13(dd,J1＝8.4Hz,J2＝2.4Hz,1H),7.07(d,J＝1.8Hz,1H),6.68(d,J＝8.4Hz,1H),6.03-6.02(m,1H),4.34(s,1H),4.32-4.31(m,2H),3.92(t,J＝5.4Hz,2H),2.51-2.49(m,2H),2.00(s,3H),1.39(s,3H),1.36(s,3H).13C{1H}NMR(150MHz,CDCl3):δ172.5,162.0,147.0,138.0,136.6,133.8,133.1,128.9,125.0,124.8,120.1,118.6,118.3,110.3,79.7,65.9,64.6,50.4,27.4,25.9,23.5,15.8.HRMS(ESI)m/z:[M+H]+Calcd for C24H26N3O2388.2020；Found 388.2013.
向15mL反应管中，依次加入4e(38.4mg,0.1mmol)、2-二环己膦基-2'-(N,N-二甲胺基)联苯(5.9mg,0.015mmol)、三(二亚苄基丙酮)二钯(9.2mg,0.01mol)、叔丁醇钠(19.2mg,0.2mmol)、吗啉(26.1mg,0.3mmol)和1,4二氧六环(1mL)。抽真空充氩气，将反应体系置于100℃油浴中反应12小时。反应结束后，用硅藻土过滤，滤液用二氯甲烷萃取，有机相干燥后，抽滤、旋干，过硅胶柱分离(石油醚/乙酸乙酯＝5/1)得到黄色固体产物9(28.6mg,73％)。该化合物的表征数据如下：1H NMR(600MHz,CDCl3):δ7.88(d,J＝7.2Hz,2H),7.38(t,J＝7.8Hz,2H),7.17(t,J＝7.2Hz,1H),6.69-6.68(m,3H),4.06(br s,1H),3.86(t,J＝4.8Hz,4H),3.09-3.05(m,4H),1.98(s,3H),1.37(s,3H),1.33(s,3H).13C{1H}NMR(150MHz,CDCl3):δ172.5,162.4,146.7,141.2,138.1,138.0,128.9,125.0,118.7,116.2,111.8,111.7,79.6,67.1,51.2,50.7,26.1,23.0,15.7.HRMS(ESI)m/z:[M+H]+Calcd forC23H27N4O2391.2129；Found 391.2127.
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 (1)

1.合成吡唑啉酮螺吲哚啉类化合物的方法，其特征在于，包括如下操作：以邻烯基苯胺类化合物1和重氮吡唑啉酮类化合物2为原料，在二氯双(4-甲基异丙基苯基)钌(II)催化剂存在下，乙腈溶剂中升温100℃反应，在氩气氛围下，得到吡唑啉酮螺吲哚啉类化合物4；反应方程式表示为：
其中：R1为氢、C1-4烷基、C1-4烷氧基、卤素或氰基，R1为一元或多元取代，R2为氢、C1-4烷基或三氟甲基，R3为氢或C1-4烷基，R4为萘基、苯基或取代苯基，R5为C1-4烷基、C1-4烷氧基、苯基或取代苯基，以上所述取代苯基苯环上的取代基为C1-4烷基、C1-4烷氧基或卤素，苯环上的取代为一元或多元取代；所述邻烯基苯胺类化合物1、重氮吡唑啉酮类化合物2与催化剂摩尔比为1:1.2:0.05。
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114805171A (zh) * 2022-05-05 2022-07-29 河南师范大学 N-芳基吲哚类化合物及其合成方法
CN115124542A (zh) * 2022-07-08 2022-09-30 河南师范大学 羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法
CN115197228A (zh) * 2022-07-13 2022-10-18 河南师范大学 吡唑啉酮[螺]二氢酞嗪和1,3-茚二酮[螺]二氢酞嗪类化合物的合成方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114805171A (zh) * 2022-05-05 2022-07-29 河南师范大学 N-芳基吲哚类化合物及其合成方法
CN115124542A (zh) * 2022-07-08 2022-09-30 河南师范大学 羟基苯取代吡唑酮并吲唑[螺]吡唑酮类化合物的合成方法
CN115197228A (zh) * 2022-07-13 2022-10-18 河南师范大学 吡唑啉酮[螺]二氢酞嗪和1,3-茚二酮[螺]二氢酞嗪类化合物的合成方法

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
Catalytic System-Controlled Divergent Reaction Strategies for the Construction of Diversified Spiropyrazolone Skeletons from Pyrazolidinones and Diazopyrazolones;Feifei Fang等;《Angew. Chem. Int. Ed.》;第60卷;21327-21333 *
Co(III), Rh(III) & Ir(III)-Catalyzed Direct C􀀀 H Alkylation/Alkenylation/Arylation with Carbene Precursors;Saiprasad Nunewar等;《Chem Asian J.》;第16卷;443-459 *
Evaluation of the Antibacterial Activity of Cellulose Nanofibers/Polylactic Acid Composites Coated With Ethanolic Extract of Propolis;Ali Abdulkhani等;《POLYMER COMPOSITES》;13-19 *
Recent quinone diazide based transformations via metal–carbene formation;Satabdi Bera等;《New J. Chem.》;第45卷;10135-10149 *
RONALDT . COUTTS等.Derivatives of 2Pyrazolin-5-one. 111. The Preparation and Properties of Some l'-Phenylspiro[indoline-2,4'-[2]pyrazoline]-5'-ones.《CAN. J. CHEM.》.1975,第53卷3645-3655. *
Straightforward Construction and Functionalizations of Nitrogen- Containing Heterocycles Through Migratory Insertion of Metal- Carbenes/Nitrenes;Satabdi Bera等;《Chem. Rec.》;第21卷;3411-3428 *
Synthesis of N‑Arylindoles from 2‑Alkenylanilines and Diazonaphthalen-2(1H)‑ones through Simultaneous Indole Construction and Aryl Introduction;Caiyun Yu等;《The Journal of Organic Chemistry》;第87卷;7392-7404 *

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