CN110528020A - 一种电催化下异噁唑并异喹啉酮衍生物的制备方法 - Google Patents
一种电催化下异噁唑并异喹啉酮衍生物的制备方法 Download PDFInfo
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- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 238000006555 catalytic reaction Methods 0.000 title claims abstract description 13
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- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
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Abstract
本发明公开了属于有机合成技术领域的一种电催化下异噁唑并异喹啉酮衍生物的制备方法。所述方法为：向反应器中，加入摩尔比为1:1的取代N‑烷氧基苯甲酰胺类物质与四正丁基六氟磷酸铵，加入95％乙醇作为溶剂，通过电催化策略促进反应进行。待反应完毕后，使用旋转蒸发仪浓缩得到粗产物，再经过硅胶柱层析分离得到目标产物。本发明提供的多取代异噁唑并异喹啉酮衍生物的合成方法具有科学合理，合成途径绿色环保，无需金属催化剂；反应溶剂为95％乙醇，代替了有毒溶剂；底物在弱电流下即可反应；合成方法简单，反应快速；目标化合物收率高，产品易于纯化等特点。其反应方程式如下：
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种电催化下异噁唑并异喹啉酮衍生物的制备方法。
背景技术
异喹啉酮类、异噁唑类化合物在自然界中广泛存在，其衍生物具有多种生物活性以及药用价值：如抗高血压、抗心律失常、抗肿瘤、抗抑郁、抗菌、抗血栓、舒张血管等多种生物活性；((a)Chem.Abstr.1987,106,159297.(b)J.Med.Chem.1987,30,2208.(c)Bioorg.Med.Chem.Lett.2006,16,3180.)氯唑西林、伐地考昔、苯唑西林、氟氯西林、达那唑、双氯西林等众多的药物分子中也都存在异噁唑结构。((a)J.Med.Chem.2000,43,775-777.(b)J.Med.Chem.2000,43,1661-1663.(c)J.Heterocycl.Chem.1976,13,449-453.)
异噁唑并异喹啉酮衍生物作为异喹啉酮和异噁唑这两种化合物的结合，很可能同时具备这两种化合物的生物活性以及药用价值。因此，发展一种快速高效地合成异噁唑并异喹啉酮衍生物的新方法具有重要的实用意义。
兰州大学于炜课题组报道了合成异噁唑并异喹啉酮衍生物的方法：在铜催化下连有炔基的N-烷氧基苯甲酰胺类物质分子内环化合成异噁唑并异喹啉酮衍生物。(ACSCatal.2018,8,8925-8931)反应式见式Ⅰ：
上述方法具有使用金属催化剂以及有毒溶剂、反应时间长等明显的缺陷。
发明内容
为了克服上述合成异噁唑并异喹啉酮衍生物现有技术的缺陷，本发明提供了一种在电催化促进下制备多取代异噁唑并异喹啉酮衍生物的方法。
电催化合成反应具有很多显著的优势：可以避免使用有毒或难以处理的催化剂，电子是绿色的反应试剂，反应产物纯度高容易分离，对环境几乎无污染；在电催化反应中，可通过改变电极电压或电流来调控反应速率以避免副反应的发生，从而提高目标产品的选择性以及收率。
一种电催化策略下多取代异噁唑并异喹啉酮衍生物的制备方法，所述异噁唑并异喹啉酮衍生物具有式Ⅱ所示的结构：
R1取代基团选自氢、氟、氯、叔丁基、甲基；R2取代基团选自苯基、氟、氯、甲基。其特征在于，向反应器中，加入摩尔比为1:1的取代N-烷氧基苯甲酰胺类物质与四正丁基六氟磷酸铵，加入95％乙醇作为溶剂，通过电催化策略促进反应进行。待反应完毕后，使用旋转蒸发仪浓缩得到粗产物，再经过硅胶柱层析分离得到目标产物。
其化学过程见反应式Ⅲ：
所述的取代N-烷氧基苯甲酰胺、四正丁基六氟磷酸铵的摩尔比值为1：1。所述溶剂为95％乙醇，通过电催化策略促进反应进行，所用电流为2mA，反应温度80℃，反应时间为4h。
本发明的有益效果为：本发明提供的多取代异噁唑并异喹啉酮衍生物合成方法科学合理，提供了一种合成多取代异噁唑并异喹啉酮衍生物新途径，通过本方法得到了具有多种取代基的异噁唑并异喹啉酮衍生物，其特点为：合成途径绿色环保，无需金属催化剂；反应溶剂为95％乙醇，代替了有毒溶剂；底物在弱电流下即可反应；合成方法简单，反应快速；目标化合物收率高，产品易于纯化。
附图说明
图1为实施例2制备的化合物2b的NMR图谱；
图2为实施例6制备的化合物2f的NMR图谱；
图3为实施例9制备的化合物2i的NMR图谱。
具体实施方式
下面结合附图和具体的实施例对本发明进一步详细的说明：
下述实施例中所述试验方法，如无特殊说明，均为常规方法；所述试剂和材料，如无特殊说明，均可从商业途径获得。
实施例1
异噁唑并异喹啉酮衍生物2a的制备
向10mL无隔膜电解槽加入N-烷氧基苯甲酰胺1a(0.1mmol,26.5mg)、四正丁基六氟磷酸铵(0.1mmol，38.7mg)，阴、阳电极均采用石墨毡电极(2cm x 1cm x 0.5cm)。后向体系充换氮气，加入95％乙醇(5mL)。于80℃、2mA恒定电流下进行电解，反应4h。反应完毕后，使用旋转蒸发仪除去溶剂得到粗产物，粗产物经柱层析分离(200-300目硅胶，石油醚/乙酸乙酯＝1/1)，使用旋转蒸发仪除去溶剂，得到目标产物无取代异噁唑并异喹啉酮衍生物2a，其收率为93％。
谱图解析数据2a:
1H NMR(CDCl3,400MHz):δ8.54(d,J＝7.1Hz,1H),7.59-7.43(m,5H),7.38-7.32(m,3H),4.58(t,J＝7.6Hz,2H),3.39(t,J＝7.6Hz,2H)；13C NMR(CDCl3,100MHz):δ153.95,136.20,135.02,132.52,131.63,130.31,128.93,128.10,127.47,126.32,126.30,124.71,113.03,69.55,32.46.
实施例2
用1b代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2b:
1H NMR(500MHz,CDCl3):δ8.51(d,J＝8.0Hz,1H),7.56(d,J＝7.6Hz,1H),7.40-7.32(m,4H),7.27(d,J＝6.7Hz,2H),4.54(t,J＝7.6Hz,2H),3.24(t,J＝7.6Hz,2H)；13C NMR(125MHz,CDCl3)δ153.12,137.66,135.25,135.03,132.48,130.51,130.18,128.78,128.24,127.67,126.94,126.47,111.44,69.50,33.19.
实施例3
用1c代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2c:
1H NMR(500MHz CDCl3):δ8.47(d,J＝3.6Hz,1H),7.53-7.49(m,2H),7.48–7.42(m,2H),7.34-7.28(m,3H),4.58(t,J＝7.6Hz,2H),3.39(t,J＝7.6Hz,2H)；13C NMR(125MHz,CDCl3):δ152.76,134.51,134.43,132.89,132.53,132.02,130.14,129.01,128.29,127.29,126.71,126.34,112.60,69.69,32.36
实施例4
用1d代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2d:
1H NMR(500MHz,CDCl3):δ8.52(d,J＝2.0Hz,1H),7.61(dd,J＝8.6,2.1Hz,1H),7.49(t,J＝7.3Hz,2H),7.44(t,J＝7.3Hz,1H),7.38–7.29(m,3H),4.56(t,J＝7.5Hz,2H),3.38(t,J＝7.5Hz,2H),1.38(s,9H)；13C NMR(125MHz,CDCl3):δ154.10,149.69,135.13,133.83,131.63,130.22,129.64,128.80,127.94,125.99,124.49,123.29,112.58,69.52,34.94,32.27,31.24.
实施例5
用1e代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2e:
1H NMR(CDCl3,500MHz):δ8.34(s,1H),7.50(t,J＝7.5Hz,2H),7.44(t,J＝6.9Hz,1H),7.36(d,J＝8.5Hz,1H),7.34(d,J＝7.8Hz,2H),7.27(d,J＝8.2Hz,1H),4.57(t,J＝7.5Hz,2H),3.38(t,J＝7.6Hz,2H),2.48(s,3H)；13C NMR(CDCl3,125MHz):δ153.90,136.50,135.16,133.90,133.17,131.51,130.27,128.86,128.00,127.00,126.23,124.65,113.02,109.98,69.58,32.32,21.20.
实施例6
用1f代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2f:
1H NMR(CDCl3,500MHz):δ8.15(d,J＝9.3,2.5Hz,1H),7.53–7.48(m,2H),7.48–7.42(m,1H),7.38–7.31(m,3H),7.28–7.24(m,1H),4.58(t,J＝7.6Hz,2H),3.38(t,J＝7.6Hz,2H)；13C NMR(CDCl3,125MHz):δ161.10(d,1JC,F＝248.2Hz),152.94,134.69,132.76,131.90,130.15,128.98,128.24,127.87(d,3JC,F＝7.6Hz),127.14(d,3JC,F＝7.4Hz),120.31(d,2JC,F＝23.5Hz),112.66,112.46(d,2JC,F＝23.2Hz),69.74,32.25.
实施例7
用1g代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2g:
1H NMR(CDCl3,400MHz):δ8.53(d,J＝8.0Hz,1H),7.59–7.53(m,1H),7.49(t,J＝7.5Hz,1H),7.37–7.28(m,3H),7.21(m,2H),4.58(t,J＝7.6Hz,2H),3.38(t,J＝7.6Hz,2H)；13C NMR(CDCl3,100MHz):δ162.51(d,1JC,F＝247.9Hz),153.93,136.17,132.77,132.05(d,3JC,F＝8.1Hz),131.75,130.88(d,4JC,F＝3.5Hz),127.54,126.42,126.27,124.47,116.04(d,2JC,F＝21.5Hz),111.94,69.53,32.44.
实施例8
用1h代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2h:
1H NMR(500MHz,CDCl3):δ8.52(dd,J＝8.0,1.4Hz,1H),7.54–7.42(m,2H),7.39-7.34(m,2H),7.31-7.28(m,1H),7.19(d,J＝7.3Hz,1H),7.05(d,J＝7.8Hz,1H),4.57(t,J＝7.7Hz,2H),3.37–3.12(m,2H),2.06(s,3H)；13C NMR(125MHz,CDCl3):δ154.00,137.59,136.08,134.05,132.35,131.69,130.58,130.46,128.60,127.40,126.41,126.24,126.16,124.50,112.21,69.45,32.12,19.63.
实施例9
用1i代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2i:
1H NMR(CDCl3,500MHz):δ8.51(d,J＝8.0Hz,1H),7.58-7.52(m,1H),7.50-7.44(m,3H),7.35-7.26(m,3H),4.58(t,J＝7.6Hz,2H),3.38(t,J＝7.6Hz,2H)；13C NMR(CDCl3,125MHz):δ153.87,135.88,134.18,133.43,132.75,131.77,131.69,129.22,127.52,126.44,126.24,124.39,111.72,69.53,32.43.
实施例10
用1j代替实例1中的1a,其他条件同实例1,实验结果见表1。
谱图解析数据2j:
1H NMR(500 MHz,CDCl3):δ8.54(d,J＝8.1 Hz,1H),7.72(d,J＝8.2 Hz,2H),7.67(d,J＝8.5 Hz,2H),7.60–7.53(m,1H),7.51–7.46(m,4H),7.44-7.37(m,3H),4.58(t,J＝7.6 Hz,2H),3.44(t,J＝7.6 Hz,2H)；13C NMR(125 MHz,CDCl3):δ153.95,140.91,140.38,136.16,133.92,132.65,131.69,130.75,128.95,127.68,127.58,127.48,127.08,126.35,126.31,124.75,112.68,69.63,32.55。
表1
Claims (2)
1.一种电催化下多取代异噁唑并异喹啉酮衍生物的制备方法，所述异噁唑并异喹啉酮衍生物具有式Ⅰ所示的结构：
R1取代基团选自氢、氟、氯、叔丁基、甲基；R2取代基团选自苯基、氟、氯、甲基。其特征在于，向反应器中，加入摩尔比为1：1的取代N-烷氧基苯甲酰胺类物质与四正丁基六氟磷酸铵，加入95％乙醇作为溶剂，通过电催化策略促进反应进行。待反应完毕后，使用旋转蒸发仪浓缩得到粗产物，再经过硅胶柱层析分离得到目标产物。其化学过程见反应式Ⅱ：
2.按照权利要求1所述的制备方法，其特征在于：所述的取代N-烷氧基苯甲酰胺、四正丁基六氟磷酸铵的摩尔比值为1:1，所述溶剂为95％乙醇，所用电流为2mA，反应温度80℃，反应时间为4h。
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111945181A (zh) * | 2020-08-17 | 2020-11-17 | 湖南科技学院 | 一种3-烷硒基喹啉酮化合物的电化学合成方法 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3838027A (en) * | 1971-09-13 | 1974-09-24 | Astra Ab | Alpha-(n-acyl)-amino acids and a process for preparing same |
| US4670109A (en) * | 1985-01-25 | 1987-06-02 | Firmenich Sa | Process for the preparation of isoxazoles |
| EP0492823A2 (en) * | 1990-12-26 | 1992-07-01 | Minnesota Mining And Manufacturing Company | Perfluorinated t-amino cyclic ethers |
| CN109369673A (zh) * | 2018-12-10 | 2019-02-22 | 青岛科技大学 | 一种异噁唑并异喹啉酮衍生物的制备方法 |
| CN109457268A (zh) * | 2018-11-29 | 2019-03-12 | 福建医科大学 | 一种电催化苯甲酰胺类化合物合成苯并噁唑的方法 |
-
2019
- 2019-09-19 CN CN201910889188.2A patent/CN110528020B/zh active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3838027A (en) * | 1971-09-13 | 1974-09-24 | Astra Ab | Alpha-(n-acyl)-amino acids and a process for preparing same |
| US4670109A (en) * | 1985-01-25 | 1987-06-02 | Firmenich Sa | Process for the preparation of isoxazoles |
| EP0492823A2 (en) * | 1990-12-26 | 1992-07-01 | Minnesota Mining And Manufacturing Company | Perfluorinated t-amino cyclic ethers |
| CN109457268A (zh) * | 2018-11-29 | 2019-03-12 | 福建医科大学 | 一种电催化苯甲酰胺类化合物合成苯并噁唑的方法 |
| CN109369673A (zh) * | 2018-12-10 | 2019-02-22 | 青岛科技大学 | 一种异噁唑并异喹啉酮衍生物的制备方法 |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| CN112410807A (zh) * | 2020-11-18 | 2021-02-26 | 青岛科技大学 | 一种电催化下四取代磺化烯醚的制备方法 |
| CN112410807B (zh) * | 2020-11-18 | 2022-05-20 | 青岛科技大学 | 一种电催化下四取代磺化烯醚的制备方法 |
| CN113355684A (zh) * | 2021-07-12 | 2021-09-07 | 青岛科技大学 | 一种电催化下多取代异喹啉盐衍生物的制备方法 |
| CN113355684B (zh) * | 2021-07-12 | 2022-10-04 | 青岛科技大学 | 一种电催化下多取代异喹啉盐衍生物的制备方法 |
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