CN108948025A - 一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法 - Google Patents

一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法 Download PDF

Info

Publication number
CN108948025A
CN108948025A CN201811006868.7A CN201811006868A CN108948025A CN 108948025 A CN108948025 A CN 108948025A CN 201811006868 A CN201811006868 A CN 201811006868A CN 108948025 A CN108948025 A CN 108948025A
Authority
CN
China
Prior art keywords
pyrrolo
spirocyclization
quinoxaline compounds
nmr
ppm
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201811006868.7A
Other languages
English (en)
Other versions
CN108948025B (zh
Inventor
严汝龙
倪吉祥
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lanzhou University
Original Assignee
Lanzhou University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Lanzhou University filed Critical Lanzhou University
Priority to CN201811006868.7A priority Critical patent/CN108948025B/zh
Publication of CN108948025A publication Critical patent/CN108948025A/zh
Application granted granted Critical
Publication of CN108948025B publication Critical patent/CN108948025B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/20—Spiro-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

本发明提供了一种新型的利用邻氨基N‑苯基吡咯为原料在比较温和的反应条件下与苯醌合成多取代螺环化的吡咯并[1,2‑a]喹喔啉化合物的方法。本发明在三氟乙酸酐为催化剂的反应条件下，通入氩气，四氢呋喃为溶剂，简单高效的合成了多取代螺环化的吡咯并[1,2‑a]喹喔啉化合物。该反应首次利用邻氨基N‑苯基吡咯和苯醌为底物合成多取代螺环化的吡咯并[1,2‑a]喹喔啉化合物，且所用催化剂为三氟乙酸酐，反应需要的步骤少。同时本发明还具有原料制备简单，操作安全，收率较高等特点，具有极大的工业化应用价值。

Description

一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法
技术领域
本发明属于有机合成技术领域，具体涉及一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法。
背景技术
螺环化合物是一类重要的有机化合物，不仅是一系列功能材料和天然产物的核心结构单元，而且在生物、医药等领域有着广泛的应用，具有细胞毒性，保肝活性，抗菌活性等潜在药效。因此螺环化合物合成的方法学研究一直被人们所关注。
近年来螺环化合物的合成方法取得了较好的进展。列举如下：
(1)以2-吡咯苯胺和靛红为底物：
Alarifi小组发现以2-吡咯苯胺和靛红为原料，用阳离子交换树脂IR120作为非均相催化剂，以水作为溶剂，加热回流，生成了螺环化的吡咯并[1,2-a]喹喔啉化合物。1
(2)以异喹啉酮和苯醌为底物：
Wang小组发现在以异喹啉酮和苯醌为原料，用[Cp*IrCl2]2作为催化剂，NaOAc作为碱，异喹啉酮和苯醌通过催化环化，生成了螺环化的异喹啉酮化合物。2
(3)以多取代噻吩，二苯乙炔和苯醌为底物：
Sahoo小组用多取代噻吩，二苯乙炔和苯醌为原料，以[RuCl2(p-cymene)]2作为催化剂，通过催化环化形成螺环化的异喹啉酮化合物。3
(4)以甲基对苯醌，叠氮基三甲基硅烷和N-碘代丁二酰亚胺为底物：
Yao小组发现以甲基对苯醌，叠氮基三甲基硅烷和N-碘代丁二酰亚胺为原料，用过氧化苯甲酸叔丁酯作为氧化剂，通过氧化环化生成螺环化合物。4
(5)以甲基对苯醌和炔丙基丙二酸酯为底物：
Lin小组发现在以甲基对苯醌和炔丙基丙二酸酯为原料，用硝酸银作为催化剂，Cs2CO3作为碱,通过催化环化生成螺环化合物。5
(6)以甲基对苯醌和乙烯基环丙烷为底物：
Yao小组发现在以甲基对苯醌和乙烯基环丙烷为原料，用Pd2(dba)3CHCl3和phosphine-thiourea作为协同催化剂，DBU(1,8-二氮杂二环十一碳-7-烯)作为添加剂，通过催化环化生成螺环化合物。6
(7)以β-炔基酮和甲基对苯醌为底物：
Jiang小组发现在以β-炔基酮和甲基对苯醌为原料，用三氟醋酸银与路易斯酸协同催化，β-炔基酮和对甲苯醌通过催化环化，生成螺环化合物。7
(8)以吲哚酮衍生物和甲氧基苯醌为底物：
Yan-Kai Liu小组发现以吲哚酮衍生物和甲氧基苯醌为底物时，基于底物的性质，利用复杂催化剂改变条件合成了多种螺环化合物。8
以上几种方法的缺点是原料制备方法复杂，反应条件苛刻，有些需要昂贵的金属催化剂或氧化剂，成本较高，无法实现工业化应用，其次至今没有提供很好的能够简单合成螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法。
本发明所要解决的技术问题在于提供简单高效全新的螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法。
为解决上述技术问题，本发明采用的技术方案是：一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法，包括以下步骤：在反应器中加入具有通式I和II的化合物，溶剂THF(四氢呋喃)，催化剂三氟乙酸酐，通入氩气，放在100℃的油浴锅中，反应48小时，薄层色谱监测反应进程，直至反应完全；减压蒸出溶剂，残渣用石油醚/乙酸乙酯＝10/1的流动相经硅胶柱层析分离纯化，得到化合物III，反应方程式如下：
方程式中：R为氢、烷基、卤素，R1为氢、烷基、芳基。
上述的这种螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法，其特征在于，用廉价易得的三氟醋酸酐作为催化剂，在催化氧化条件下与苯醌形成亚胺，进而吡咯对亚胺进行亲核环化得到最终产物。
本发明与现有技术相比具有以下优点：
1、本发明所用原料廉价易得，反应条件温和，操作简便，底物兼容性好，产率较高等优点
2、本发明利用酸催化形成亚胺、进而吡咯对亚胺进行亲核环化，生成螺环化的吡咯并[1,2-a]喹喔啉化合物。
下面通过实施例，对本发明技术方案做进一步的详细说明。具体实施方式
实施例1：本实施例的制备方法包括以下步骤：
在反应管中依次加入化合物Ia(0.30mmol)、IIa(0.45mmol)、TFAA(0.06mmol)、THF(2ml)，在100℃的油浴锅中，反应48.0h，薄层色谱监测反应进程，直至反应完全，减压蒸出溶剂，残渣用石油醚/乙酸乙酯＝10/1的流动相经硅胶柱层析分离纯化，得到化合物IIIaa，收率80％。反应方程式如下：
实施例1所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.36-7.33(d,J＝7.8Hz,1H),7.24-7.24(m,1H),7.06-7.00(m,3H),6.94-6.89(m,1H),6.81-6.78(d,J＝7.8Hz,1H),6.32-6.30(m,1H)6.19-6.15(m,2H),6.02-6.01(m,1H),4.16(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.8,148.3,132.6,126.9,125.2,124.5,123.5,120.4,116.1,116.0,114.8,110.8,106.0,53.6；HRMS calcd for C16H13N2O[M+H]+249.1023；found:249.1025.
实施例2所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.41-7.40(m,1H),7.07-7.02(m,2H),6.98-6.93(m,1H),6.81-6.79(d,J＝6.9Hz,1H),6.69-6.67(d,J＝6.6Hz,1H),6.32-6.29(m,1H),6.24-6.20(m,2H),6.02-6.01(m,1H),4.07(br s,1H),2.64(s,3H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.8,148.0,134.8,127.7,126.5,126.3,125.2,124.9,124.6,120.6,114.8,109.7,104.6,53.3,21.5；HRMS calcd for C17H15N2O[M+H]+263.1179；found:263.1170.
实施例3所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.22-7.21(m,1H),7.16(s,1H),7.05-7.02(m,2H),6.84-6.82(d,J＝7.8Hz,1H),6.70-6.67(d,J＝8.1Hz,1H),6.30-6.28(m,1H),6.18-6.15(m,2H),6.00-5.99(m,1H),4.03(br s,1H),2.34(s,3H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.9,148.4,130.2,130.1,126.9,125.8,124.5,123.8,116.1,115.9,115.4,110.7,105.9,53.7,20.9；HRMS calcd for C17H15N2O[M+H]+263.1179；found:263.1181.
实施例4所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.26-7.24(m,1H),7.21-7.20(m,1H),7.05-7.01(m,2H),6.73-6.70(m,1H),6.60(s,1H),6.29-6.27(m,1H),6.18-6.14(m,2H),6.00-5.98(m,1H),4.12(br s,1H),2.28(s,3H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.9,148.5,135.1,132.4,126.8,123.3,122.3,121.0,116.6,115.8,114.6,110.5,105.7,53.6,21.0；HRMScalcd for C17H15N2O[M+H]+263.1179；found:263.1182.
实施例5所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.21-7.20(m,1H),7.11(s,1H),7.06-7.02(m,2H),6.58(s,1H),6.28-6.27(m,1H),6.18-6.14(m,2H),6.00-5.97(m,1H),3.96(br s,1H),2.24(s,3H),2.20(s,3H)；13C NMR(100MHz,CDCl3,ppm):δ＝185.0,148.6,133.6,130.3,128.7,126.9,123.6,122.5,117.5,116.0,115.9,110.4,105.7,53.8,19.4,19.3；HRMScalcd for C18H17N2O[M+H]+277.1336；found:277.1330.
实施例6所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.28-7.25(m,1H),7.22-7.21(m,1H)，7.08-7.05(d,J＝9.9Hz,2H),6.95-6.91(m,1H),6.80-6.79(d,J＝1.8Hz,1H),6.30-6.28(m,1H),6.19-6.16(d,J＝9.9Hz,2H),6.00-5.99(m,1H),4.09(br s,1H),1.30(s,9H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.9,148.6,132.0,130.9,126.8,123.3,122.2,117.5,115.9,114.3,113.2,110.5,105.7,53.7,34.5,31.3；HRMS calcd for C20H21N2O[M+H]+305.1649；found:305.1645.
实施例7所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.90-7.89(m,1H),7.07-7.03(m,2H),6.98-6.94(m,1H),6.58-6.56(m,1H),6.45-6.43(m,1H),6.25-6.23(m,1H),6.19-6.15(m,2H),5.99-5.98(m,1H),4.17(br s,1H),3.95(s,3H)；13C NMR(100MHz,CDCl3,ppm):δ＝185.0,150.0,148.4,134.9,127.2,125.2,124.0,122.3,116.2,114.8,109.4,109.1,104.6,104.4,55.9,53.3；HRMS calcd for C17H15N2O2[M+H]+279.1128；found:279.1125.
实施例8所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.30-7.26(m,1H),7.18-7.17(m,1H),7.02-6.99(d,J＝9.9Hz,2H),6.62-6.53(m,2H),6.30(s,1H),6.18-6.15(d,J＝9.9Hz,2H),6.01-6.00(d,J＝1.8Hz,1H),4.33(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.7,161.8,158.6,147.9,134.1-134.0(d,J＝10.5Hz,1C),127.0,123.0,120.8,115.9,115.8-115.7(d,J＝9.8Hz,1C),110.9,106.8-106.5(d,J＝23.3Hz,1C),106.1,103.3-103.0(d,J＝26.3Hz,1C),53.6；HRMS calcd for C16H12FN2O[M+H]+267.0928；found:267.0931.
实施例9所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.29-7.25(m,1H),7.18-7.17(m,1H),7.02-6.99(d,J＝9.9Hz,2H),6.63-6.52(m,2H),6.31-6.29(m,1H),6.18-6.15(d,J＝9.9Hz,2H),6.01-6.00(d,J＝2.4Hz,1H),4.37(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.8,161.8-158.6(d,J＝241.5Hz,1C),148.0,134.1-134.0(d,J＝10.5Hz,1C),128.8,127.0,125.5,123.0,120.8,115.9,115.8-115.7(d,J＝9.8Hz,1C),110.9,106.8-106.5(d,J＝23.3Hz,1C),106.1,103.3-103.0(d,J＝26.3Hz,1C),53.6；HRMS calcd for C16H12FN2O[M+H]+267.0928；found:267.0930.
实施例10所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.20-7.14(m,1H),7.11-7.10(m,1H),7.02-6.99(d,J＝10.2Hz,2H),6.68-6.62(m,1H),6.33-6.31(m,1H),6.20-6.16(m,2H),6.03-6.01(m,1H),4.26(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.6,147.7,145.9-145.7(d,J＝13.5Hz,1C),142.7,129.1,127.2,123.4,120.2,116.1,111.4,106.6,105.0-104.6(d,J＝28.5Hz,1C),104.7-104.3(d,J＝29.3Hz,1C),53.5；HRMS calcd for C16H11F2N2O[M+H]+285.0834；found:285.0830.
实施例11所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.43-7.40(d,J＝8.1Hz,1H),7.26-7.25(m,1H),7.18-7.15(m,1H),7.05-6.99(m,3H),6.37-6.35(m,1H),6.21-6.17(m,2H),6.07-6.05(m,1H),4.39(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.8,147.9,133.1,127.4,123.9,117.5-117.4(d,J＝3.8Hz,1C),116.6,115.1,113.1-113.0(d,J＝3.8Hz,1C),112.1,107.3,53.8；HRMS calcd for C17H12F3N2O[M+H]+317.0896；found:317.0890.
实施例12所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.33(s,1H),7.18-7.17(m,1H),7.02-6.97(m,3H),6.74-7.71(d,J＝8.1Hz,1H),6.33-6.32(m,1H),6.20-6.16(d,J＝9.9Hz,1H),6.03-6.02(m,1H),4.20(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.7,147.9,131.2,127.1,125.2,125.1,125.0,123.5,117.0,116.1,115.1,111.4,106.6,53.6；HRMS calcd forC16H12ClN2O[M+H]+283.0633；found:283.0636.
实施例13所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝7.26(s,1H),7.20-7.19(m,1H),7.02-6.98(m,2H),6.88-6.86(m,1H),6.80-6.79(m,1H),6.33-6.31(m,1H),6.20-6.16(m,2H),6.02-6.01(m,1H),4.27(br s,1H)；13C NMR(100MHz,CDCl3,ppm):δ＝184.8,147.9,133.8,130.3,127.1,123.3,123.1,120.2,116.1,115.9,115.8,111.2,106.4,53.6；HRMS calcd forC16H12ClN2O[M+H]+283.0633；found:283.0637.
实施例14所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.28-7.26(m,1H),7.23-7.21(m,1H),7.14-7.11(m,1H),7.03-6.99(d,J＝9.9Hz,2H),6.87-6.82(m,1H),6.34-6.32(m,1H),6.23-6.18(m,2H),6.04-6.03(m,1H),4.69(br s,1H),3.83-3.80(m,2H),3.26-3.23(m,2H),2.21-2.14(m,2H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.6,147.7,129.6,127.1,125.2,123.4,120.5,119.8,113.1,111.5,106.5,53.5；HRMS calcd for C16H12ClN2O[M+H]+283.0633；found:283.0629.
实施例15所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.32(s,1H),7.16-7.15(m,1H),7.03-6.97(m,2H),6.65(s,1H),6.31-6.29(m,1H),6.20-6.14(m,2H),6.01-5.99(m,1H),4.10(br s,1H),2.30(s,3H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.7,148.0,132.7,131.2,127.1,125.2,123.4,123.3,118.0,116.0,115.3,111.1,106.3,53.6,19.6；HRMS calcd for C17H14ClN2O[M+H]+297.0789；found:297.0780.
实施例16所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,DMSO-d6,ppm):δ＝7.77-7.75(d,J＝7.2Hz,1H),7.51-7.50(m,1H),7.11(s,1H),7.01-6.97(m,2H),6.81-6.78(d,J＝10.4Hz,1H),6.25-6.23(m,1H),6.13-6.09(m,1H),5.91-5.90(m,1H),4.15(br s,1H)；13C NMR(75MHz,DMSO-d6,ppm):δ＝185.5,156.7,153.5,149.6,134.7-134.6(d,J＝9.8Hz,1C),126.6,123.3,121.3,117.6-116.8(d,J＝64.5Hz,1C),111.7,108.7-108.5(d,J＝20.0Hz,1C),106.5,104.1-103.8(d,J＝26.3Hz,1C),53.3；HRMS calcd for C16H11ClFN2O[M+H]+301.0539；found:301.0541.
实施例17所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.27-7.24(m,1H),7.20-7.19(m,1H),7.03-6.98(m,2H),6.89-6.85(m,1H),6.80-6.79(d,J＝2.4Hz,1H),6.33-6.31(m,1H),6.21-6.16(m,2H),6.03-6.01(m,1H),4.27(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.5,147.5,132.2,128.2,127.3,123.8,123.3,123.1,117.0,116.3,116.2,111.7,106.9,53.5；HRMScalcd for C16H11Cl2N2O[M+H]+317.0243；found:317.0247.
实施例18所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.21-7.18(m,2H),7.02-6.94(m,4H),6.32-6.30(m,1H),6.19-6.15(m,2H),6.02-6.01(m,1H),4.31(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.7,147.9,134.0,127.0,123.5,123.2,123.0,118.7,117.7,116.0,115.9,111.2,106.5,53.6；HRMS calcd for C16H12BrN2O[M+H]+327.0128；found:327.0130.
实施例19所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.36-7.35(m,1H),7.03-6.98(m,2H),6.95-6.94(m,1H),6.84-6.83(m,1H),6.33-6.30(m,1H),6.26-6.20(m,2H),6.03-6.01(m,1H),4.13(br s,1H),2.61(s,3H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.7,147.4,136.0,128.2,127.9,127.1,126.0,123.9,120.5,117.5,117.3,110.1,105.0,53.2,21.3；HRMS calcdfor C17H14BrN2O[M+H]+341.0284；found:341.0290.
实施例20所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.90-7.88(m,1H),7.71-7.69(m,1H),7.09-7.06(m,1H),7.03-7.02(m,1H),6.99-6.94(m,2H),6.32-6.30(m,1H),6.17-6.12(m,2H),6.05-6.04(m,1H),4.41(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.8,148.3,138.8,137.0,128.2,126.7,123.1,122.3,120.9,117.0,111.3,107.6,53.5；HRMS calcd for C15H12N3O[M+H]+250.0975；found:250.0976.
实施例21所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.71(s,1H),7.67-7.66(m,1H),7.03-6.98(m,2H),6.89-6.88(m,1H),6.31-6.29(m,1H),6.18-6.13(m,2H),6.04-6.02(m,1H),4.20(brs,1H),2.27(s,3H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.7,148.2,138.8,135.2,130.6,127.7,126.7,123.0,116.8,110.9,107.2,53.6,18.0；HRMS calcd for C16H14N3O[M+H]+264.1132；found:264.1137.
实施例22所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.67-7.65(m,1H),7.06-6.95(m,4H),6.33-6.31(m,1H),6.18-6.15(m,2H),6.06-6.05(m,1H),4.29(br s,1H)；13C NMR(75MHz,CDCl3,ppm):δ＝184.5,147.7,139.2,136.2,126.9,126.8,124.7,123.0,120.5,117.5,111.7,108.2,53.5；HRMS calcd for C15H11ClN3O[M+H]+284.0585；found:284.0588.
实施例23所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.36-7.33(d,J＝7.8Hz,1H),7.23-7.22(m,1H),7.05-6.99(m,2H),6.93-6.88(m,1H),6.83-6.77(m,2H),6.31-6.29(m,1H),6.19-6.15(d,J＝9.6Hz,1H),5.99-5.97(m,1H),4.14(br s,1H),1.87(s,3H)；13C NMR(75MHz,CDCl3,ppm):δ＝185.6,148.2,143.7,133.4,132.9,127.0,125.2,124.5,124.3,120.2,116.1,115.8,114.8,110.7,105.5,53.9,15.6；HRMS calcd for C17H15N2O[M+H]+263.1179；found:263.1171.
实施例24所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.34-7.31(d,J＝7.5Hz,1H),7.21-7.20(m,1H),7.02-6.97(m,1H),6.91-6.86(m,1H),6.83-6.82(m,1H),6.78-6.76(m,1H),6.29-6.27(m,1H),6.01-5.98(d,J＝9.9Hz,1H),5.94-5.92(m,1H),4.13(br s,1H),1.24(s,9H)；13C NMR(75MHz,CDCl3,ppm):δ＝185.1,146.0,144.8,141.9,133.0,127.8,125.1,124.7,124.5,120.1,116.0,115.7,114.7,110.7,105.5,54.0,34.6,29.1；HRMS calcd for C20H21N2O[M+H]+305.1649；found:305.1640.
实施例25所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(300MHz,CDCl3,ppm):δ＝7.34-7.31(d,J＝7.8Hz,1H),7.23-7.22(m,1H),7.02-6.97(m,1H),6.87-6.81(m,1H),6.76-6.73(m,1H),6.71(s,1H),6.30-6.26(m,1H),6.04(s,1H),5.89-5.85(m,1H),4.04(br s,1H),2.98-2.89(m,1H),1.92(s,3H),1.03-1.02(d,J＝1.5Hz,3H),1.01-1.00(d,J＝1.5Hz,3H)；13C NMR(75MHz,CDCl3,ppm):δ＝185.2,159.1,142.2,140.5,133.3,126.7,125.2,124.6,123.4,119.2,115.0,114.9,114.5,106.2,56.7,25.9,21.5,19.1；HRMS calcd for C20H21N2O[M+H]+305.1649；found:305.1655.
实施例26所得产品的结构、核磁、高分辨质谱数据如下：
1H NMR(400MHz,CDCl3,ppm):δ＝8.15-8.13(d,J＝7.6Hz,1H),7.80-7.78(d,J＝8.0Hz,1H),7.59-7.54(m,1H),7.49-7.45(m,1H),7.41-7.39(d,J＝8.0Hz,1H),7.24-7.23(m,1H),7.12-7.09(d,J＝10.0Hz,1H),7.05-7.01(m,1H),6.94-6.90(m,1H),6.78-6.76(m,1H),6.23-6.22(m,1H),6.18-6.15(d,J＝10.4Hz,1H),5.53-5.51(m,1H),4.31(br s,1H)；13C NMR(100MHz,CDCl3,ppm):δ＝183.9,148.4,144.8,133.6,133.3,130.8,129.6,128.6,128.2,126.2,125.3,124.5,120.1,115.9,115.2,114.8,110.9,107.0,54.9；HRMS calcdfor C20H15N2O[M+H]+299.1179；found:299.1182.
参考文献：
1.A.Kamal,K.S.Babu,J.Kovvuri,V.Manasa,A.Ravikumar,A.Alarifi,TetrahedronLetters.,2015,56,7012.
2.T.Zhou,L.-B.Li,B.Li,H.B.Song,B.Q.Wang,Org.Lett.,2015,17,4204.
3.K.Mukherjee,M.Shankar,K.Ghosh,A.K.Sahoo,Org.Lett.,2018,20,1914
4.R.Pan,L.Y.Hu,C.Han,A.J.Lin,H.Q.Yao,Org.Lett.,2018,20,1974.
5.Z.B.Yuan,L.N.Liu,R.Pan,H.Q.Yao,A.J.Lin,J.Org.Chem.,2017,82,8743.
6.Z.B.Yuan,W.W.Wei,A.J.Lin,H.Q.Yao,Org.Lett.,2016,18,3370
7.S.Liu,X.-C.Lan,K.Chen,W.-J.Hao,G.G.Li,S.-J.Tu,B.Jiang,Org.Lett.,2017,19,3831.
8.L.Qiao,Z.-W.Duan,X.-N.Wu,D.-H.Li,Q.-Q.Gu,Y.-K.Liu,Org.Lett.,2018,20,1630.

Claims (5)

1.一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法，包括以下步骤：在反应器中加入具有通式I和II的化合物，溶剂，催化剂，通入氩气，放在100℃的油浴锅中，反应48.0h，薄层色谱监测反应进程，直至反应完全；减压蒸出溶剂，残渣用石油醚/乙酸乙酯＝10/1的流动相经硅胶柱层析分离纯化，得到化合物III，反应方程式如下
方程式中：R选自氢、烷基、卤素，R1选自氢、烷基、芳基。上述的一种螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法，其特征在于，用廉价易得的三氟乙酸酐作为催化剂，在催化氧化条件下与苯醌形成亚胺，进而吡咯对亚胺进行亲核环化得到最终产物。
2.螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法，其特征在于，所述催化剂为醋酸，特戊酸，三氟乙酸，三氟醋酸酐，三氟醋酸银，[双(三氟乙酰氧基)碘]苯，对甲苯磺酸。
3.根据权利要求1所述的一种多取代螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法，其特征在于，所述溶剂为四氢呋喃，乙腈，二氯乙烷，乙醚，丙酮，甲苯。
4.根据权利要求1所述的一种多取代螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法，其特征在于，所述通式化合物I和II、催化剂的用量的摩尔比为1:1.0-2.0:0.1-0.5
5.根据权利要求1所述的一种多取代螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法，其特征在于，所述反应温度为80-120℃。
CN201811006868.7A 2018-08-30 2018-08-30 一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法 Active CN108948025B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201811006868.7A CN108948025B (zh) 2018-08-30 2018-08-30 一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201811006868.7A CN108948025B (zh) 2018-08-30 2018-08-30 一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法

Publications (2)

Publication Number Publication Date
CN108948025A true CN108948025A (zh) 2018-12-07
CN108948025B CN108948025B (zh) 2021-05-04

Family

ID=64474955

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201811006868.7A Active CN108948025B (zh) 2018-08-30 2018-08-30 一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法

Country Status (1)

Country Link
CN (1) CN108948025B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110003147A (zh) * 2019-05-10 2019-07-12 兰州大学 一种多取代的3-亚苄基四氢呋喃化合物的制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108409743A (zh) * 2018-03-07 2018-08-17 兰州大学 一种烷基腈取代的吡咯并[1,2-a]喹喔啉化合物的制备方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108409743A (zh) * 2018-03-07 2018-08-17 兰州大学 一种烷基腈取代的吡咯并[1,2-a]喹喔啉化合物的制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MAN WANG，等: "Expedient synthesis of pyrrolo[1,2-a]quinoxalines through one-pot three-component reactions of o-phenylenediamines，2-alkoxy-2,3-dihydrofurans and ketones", 《TETRAHEDRON》 *
ZHENYU AN,等: "FeCl3-Catalyzed synthesis of pyrrolo[1,2-a]-quinoxaline derivatives from 1-(2-aminophenyl)-pyrroles through annulation and cleavage of cyclic ethers", 《CHEM. COMMUN.》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110003147A (zh) * 2019-05-10 2019-07-12 兰州大学 一种多取代的3-亚苄基四氢呋喃化合物的制备方法
CN110003147B (zh) * 2019-05-10 2023-05-09 兰州大学 一种多取代的3-亚苄基四氢呋喃化合物的制备方法

Also Published As

Publication number Publication date
CN108948025B (zh) 2021-05-04

Similar Documents

Publication Publication Date Title
CN101798279B (zh) 铁催化的吡咯及吡咯并环类化合物的制备方法
CN105175328B (zh) 一种利用芳香胺、芳香醛、酮合成喹啉衍生物的方法
CN111808071B (zh) 一种铑催化吡啶与炔烃环化合成多取代氨基异喹啉化合物的方法
CN106866670A (zh) 一种螺[3,5`‑吡咯[2,1‑a]异喹啉‑氧化吲哚]类化合物及其制备方法
CN104844601B (zh) 一种合成光学活性螺环氧化吲哚四氢喹啉衍生物的方法
CN108948025B (zh) 一种新型螺环化的吡咯并[1,2-a]喹喔啉化合物的制备方法
CN108864164B (zh) 一种一级胺导向的2-炔基吲哚类化合物的合成方法
CN111362895A (zh) 一种萘并呋喃衍生物的合成方法、萘并呋喃衍生物及应用
CN110483387B (zh) 一种一锅法合成烟酰亚胺酰胺衍生物的方法
Arai et al. Palladium-catalyzed intramolecular CH arylation of five-membered N-heterocycles
CN108409743B (zh) 一种烷基腈取代的吡咯并[1,2-a]喹喔啉化合物的制备方法
Yavari et al. A Synthesis of Novel Perinaphthenones from Acetylenic Esters and Acenaphthoquinone–Malononitrile Adduct in the Presence of Triphenylphosphine
CN113880781B (zh) 一种以葡萄糖为碳源合成3-三氟甲基取代的1,2,4-三氮唑化合物的方法
Zhegalova et al. Wolff rearrangement of β‐alkynyl‐α‐diazo‐β‐ketoesters: light‐induced acetylene–allene isomerization and its use for activation of enediynes
CN110240572B (zh) 一种反式-1,1-环丙烷二羧酸酯的合成方法
Nandakumar et al. Palladium-catalyzed intramolecular hydroarylation of 2-bromobenzyl propargyl ethers: A new access to exocyclic isochromans
Kurohara et al. Synthesis of Alkoxycarbonyldifluoromethyl-Substituted Semisquarates and Their Transformations
Babaoglu et al. Indium-mediated Blaise-type reaction of bromomalonates with nitriles and isocyanates
CN107382782B (zh) 一种多芳基取代萘酚衍生物的合成方法
CN108218758B (zh) 一种2，4-二取代吡咯衍生物的制备方法
Silva et al. 1, 6-Conjugate Addition of Carbon Nucleophiles to (E)-2-Styrylchromones: Unexpected Synthesis of a Stereochemically Complex Pentasubstituted Spirocyclohexane
CN107216331B (zh) 一种四氢萘啶并四氢喹唑啉衍生物及其合成方法和应用
CN111978167A (zh) 一种多取代环己-2-烯酮的一步合成方法
CN105198806A (zh) 一种利用芳香胺、二酮合成喹啉衍生物的方法
CN108558751B (zh) 3-硝基喹啉衍生物的合成工艺

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant