CN108822030A - 一种合成1,2,3,4-四氢喹啉类化合物的方法 - Google Patents

一种合成1,2,3,4-四氢喹啉类化合物的方法 Download PDF

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CN108822030A
CN108822030A CN201810856091.7A CN201810856091A CN108822030A CN 108822030 A CN108822030 A CN 108822030A CN 201810856091 A CN201810856091 A CN 201810856091A CN 108822030 A CN108822030 A CN 108822030A
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quinoline
methylene chloride
tetrahydroquinolinesas
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杨春华
杨占涛
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Anyang Normal University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C07D215/06—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/18—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

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Abstract

本发明公开了一种1,2,3,4‑四氢喹啉类化合物的合成方法，属有机化学合成技术领域。该方法以单质碘为催化剂，硼烷为还原剂，用喹啉类化合物催化还原反应制得。与现有合成方法相比，本发明方法最大的特点是使用廉价的I2作催化剂，无需金属参与反应，反应条件温和，快速高效，催化效率高，操作简单，选择性好，产物转化率高，达80%以上，极具推广应用价值，有利于工业化生产。

Description

一种合成1,2,3,4-四氢喹啉类化合物的方法
技术领域
本发明属于有机化学合成技术领域，涉及1,2,3,4-四氢喹啉类化合物的合成方法，具体涉及非金属催化条件下，采用硼烷作还原剂，实现喹啉还原合成1,2,3,4-四氢喹啉类化合物。
背景技术
四氢喹啉骨架广泛存在于药物、农产品及天然产物中，往往具有很好的生物活性。发展和探索高效合成四氢喹啉类化合物的合成新方法具有重要的意义，喹啉的还原作为一种高效的方法，得到了较好的发展。喹啉的还原大都采用氢气作还原剂，且需要稀有金属作催化剂，该方法往往需要高温高压，反应条件较为苛刻(J.Am.Chem.Soc.,2011,133,9878–9891；J.Am.Chem.Soc.,2011,133,7547–7562；J.Am.Chem.Soc.,2003,125,10536–10537；J.Am.Chem.Soc.,2015,137,11718–11724；Angew.Chem.,Int.Ed.,2008,47,8464–8467；Chem.Rev.,2012,112,2557–2590；Angew.Chem.,Int.Ed.,2017,56,3216–3220)。近年来采用硼烷或者硅烷作还原剂的方法也有报道，这些方法中需要较为昂贵的催化剂，稀有金属或者B(C6F5)3(Angew.Chem.,Int.Ed.,2017,56,7720–7738；Angew.Chem.,Int.Ed.,2013,52,10076–10079；Angew.Chem.,Int.Ed.,2017,56,5817–5820；J.Am.Chem.Soc.,2014,136,16780–16783；J.Am.Chem.Soc.,2015,137,15176–15184；J.Am.Chem.Soc.,2015,137,4916–4919；Nat.Chem.,2014,6,1100)。目前，为满足工业化生产需求，探索采用廉价催化剂合成1,2,3,4-喹啉类化合物的方法尤为必要。
发明内容
本发明目的在于克服现有技术缺陷，提供一种单质碘催化喹啉还原合成1,2,3,4-喹啉类化合物的方法，实现适用性广、收率高且催化剂廉价的工业化生产需求。
为实现上述目的，本发明采用如下技术方案：
所述1,2,3,4-四氢喹啉的制备方法通过如下步骤实现：在氮气气氛下，将式I所示的喹啉类化合物，催化剂单质碘，还原剂频哪醇硼烷溶于有机溶剂中，搅拌反应。反应结束后分离纯化，即得到式II所示的1,2,3,4-四氢喹啉类化合物。
式I和式II中，R代表氢，C1-4烷基，苯基，C1-4烷氧基，卤素，硝基，C1-4酯基，R为在喹啉苯环或杂环上任意单取代。
具体的，所述催化剂I2的加入量优选为喹啉化合物摩尔量的20％；还原剂频哪醇硼烷的用量优选为喹啉化合物摩尔量的4倍。进一步优选，所述溶剂为二氯甲烷或者甲苯。
本发明优点在于：反应中使用非金属I2作催化剂，催化效率高，且反应条件温和，操作简单，选择性好，产物转化率高，达80％以上，适用性广。与现有合成方法相比，本发明方法最大的特点是使用廉价的I2作催化剂，无需金属参与反应，反应条件温和，快速高效，极具推广应用价值，有利于工业化生产。
具体实施方式
为了更好的解释本发明的实施，对技术方案进一步地详细介绍，但本发明的保护范围并不限于此。
实施例1
1,2,3,4-四氢喹啉的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和喹啉(0.25mmol)，置换空气，分别加入二氯甲烷(1mL)和频哪醇硼烷(1mmol)；室温下搅拌24小时后，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到1,2,3,4-四氢喹啉，无色油状物，收率91％。1H NMR(400MHz,CDCl3)δ7.00–6.96(m,2H),6.63(t,J＝7.4Hz,1H),6.49(d,J＝7.8Hz,1H),3.72(brs,1H),3.33–3.30(m,2H),2.79(t,J＝6.4Hz,2H),1.99–1.93(m,2H)；13CNMR(100MHz,CDCl3)δ144.9,129.6,126.8,121.5,117.0,114.3,42.1,27.1,22.3.
实施例2
2-苯基-四氢喹啉的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和2-苯基喹啉(0.25mmol)，置换空气，分别加入甲苯(1mL)和频哪醇硼烷(1mmol)；加热到100℃搅拌24小时后，反应液冷却至室温，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到2-苯基-四氢喹啉，无色油状物，收率84％。1H NMR(400MHz,CDCl3)δ7.44–7.27(m,5H),7.05(t,J＝7.4Hz,2H),6.69(t,J＝7.4Hz,1H),6.58(d,J＝7.7Hz,1H),4.49–4.46(m,1H),4.07(brs,1H),2.97–2.93(m,1H),2.81–2.76(m,1H),2.20–2.13(m,1H),2.08–1.99(m,1H).13C NMR(100MHz,CDCl3)δ144.9,144.8,129.4,128.7,127.6,127.0,126.7,121.0,117.3,114.1,56.4,31.1,26.5.
实施例3
3-氯-四氢喹啉的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和3-氯喹啉(0.25mmol)，置换空气，分别加入二氯甲烷(1mL)和频哪醇硼烷(1mmol)；室温下搅拌24小时后，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到3-氯-四氢喹啉，黄色油状物，收率81％。1H NMR(400MHz,CDCl3)δ7.07(dd,J＝11.3,3.9Hz,1H),7.00(d,J＝7.2Hz,1H),6.72(dd,J＝10.7,4.1Hz,1H),6.58(d,J＝8.0Hz,1H),4.47–4.42(m,1H),3.72(brs,1H),3.65–3.61(m,1H),3.41(dd,J＝11.8,7.5Hz,1H),3.32(dd,J＝16.3,4.4Hz,1H),3.09(dd,J＝16.3,7.6Hz,1H).13C NMR(100MHz,CDCl3)δ142.9,129.7,127.6,118.2,118.1,114.5,52.6,48.9,37.2.
实施例4
4-甲基-四氢喹啉的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和4-甲基-喹啉(0.25mmol)，置换空气，分别加入二氯甲烷(1mL)和频哪醇硼烷(1mmol)；室温下搅拌24小时后，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到4-甲基-四氢喹啉，无色油状物，收率80％。1H NMR(400MHz,CDCl3)δ7.08(d,J＝7.5Hz,1H),7.03–6.95(m,1H),6.68–6.61(m,1H),6.50(d,J＝8.0Hz,1H),3.87(brs,1H),3.36–3.29(m,2H),3.02–2.92(m,1H),2.01–1.96(m,1H),1.72–1.70(m,1H),1.31(d,J＝7.0Hz,3H).13C NMR(100MHz,CDCl3)δ144.4,128.6,126.9,126.7,117.1,114.3,39.1,30.3,30.0,22.8.
实施例5
5-硝基-四氢喹啉的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和5-硝基-喹啉(0.25mmol)，置换空气，分别加入二氯甲烷(1mL)和频哪醇硼烷(1mmol)；室温下搅拌24小时后，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到5-硝基-四氢喹啉，黄色固体，收率82％。1H NMR(400MHz,CDCl3)δ7.12(d,J＝8.0Hz,1H),7.03(t,J＝8.0Hz,1H),6.65(d,J＝8.0Hz,1H),4.22(brs,1H),3.35–3.32(m,2H),2.93(t,J＝6.4Hz,2H),1.95–1.89(m,2H).13C NMR(100MHz,CDCl3)δ150.5,146.1,126.7,118.0,115.2,112.3,41.0,24.0,21.2.
实施例6
6-甲氧基-四氢喹啉的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和6-甲氧基-喹啉(0.25mmol)，置换空气，分别加入二氯甲烷(1mL)和频哪醇硼烷(1mmol)；室温下搅拌24小时后，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到6-甲氧基-四氢喹啉，无色油状物，收率85％。1H NMR(400MHz,CDCl3)δ6.62–6.57(m,2H),6.47(d,J＝8.5Hz,1H),3.74(s,3H),3.28–3.25(m,2H),2.77(t,J＝6.5Hz,2H),1.97–1.91(m,2H).13C NMR(100MHz,CDCl3)δ151.8,138.9,122.9,115.6,114.9,112.9,55.8,42.3,27.2,22.4.
实施例7
1,2,3,4-四氢喹啉-6-甲酸甲酯的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和喹啉-6-甲酸甲酯(0.25mmol)，置换空气，分别加入二氯甲烷(1mL)和频哪醇硼烷(1mmol)；室温下搅拌24小时后，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到1,2,3,4-四氢喹啉-6-甲酸甲酯，白色固体，收率88％。1H NMR(400MHz,CDCl3)δ7.65–7.64(m,2H),6.40–6.38(m,1H),4.41(brs,1H),3.84(s,3H),3.35–3.32(m,2H),2.76(t,J＝6.3Hz,2H),1.95–1.89(m,2H).13C NMR(100MHz,CDCl3)δ167.6,148.9,131.3,129.2,119.9,117.3,112.7,51.5,41.7,27.0,21.4.
实施例8
8-氟-四氢喹啉的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和8-氟-喹啉(0.25mmol)，置换空气，分别加入二氯甲烷(1mL)和频哪醇硼烷(1mmol)；室温下搅拌24小时后，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到8-氟-四氢喹啉，黄色油状物，收率87％。1H NMR(400MHz,CDCl3)δ6.83–6.74(m,2H),6.54–6.49(m,1H),4.01(brs,1H),3.37–3.34(m,2H),2.80(t,J＝6.4Hz,2H),2.00–1.94(m,2H).13C NMR(100MHz,CDCl3)δ152.2,149.9,133.4,133.2,124.6,124.6,123.7,115.7,115.6,112.4,112.2,41.4,26.7,21.9.
实施例9
8-溴-四氢喹啉的具体合成步骤如下：
在反应瓶中加入单质碘(0.05mmol)和8-溴-喹啉(0.25mmol)，置换空气，分别加入二氯甲烷(1mL)和频哪醇硼烷(1mmol)；室温下搅拌24小时后，加入二氯甲烷(5mL)稀释反应液，分离有机相，水相用二氯甲烷(5mL)萃取，合并有机相，无水硫酸钠干燥，过滤，浓缩得粗品，粗品经柱层析分离(乙酸乙酯:石油醚1％～10％)得到8-溴-四氢喹啉，无色油状物，收率85％。1H NMR(400MHz,CDCl3)δ7.22(d,J＝8.5Hz,1H),6.87(d,J＝7.4Hz,1H),6.44(t,J＝7.7Hz,1H),4.41(brs,1H),3.39–3.36(m,2H),2.76(t,J＝6.3Hz,2H),1.94–1.88(m,2H)；13CNMR(100MHz,CDCl3)δ141.8,130.1,128.5,122.9,117.0,108.8,42.1,27.5,21.8.。

Claims (2)

1.一种1,2,3,4-四氢喹啉类化合物的合成方法，其特征在于，通过如下步骤实现：在氮气气氛下，将式I所示的喹啉类化合物，催化剂单质碘，还原剂频哪醇硼烷溶于有机溶剂中，搅拌反应，反应后分离纯化，得到式II所示的1,2,3,4-四氢喹啉类化合物；
式I和式II中，
R代表氢，C1-4烷基，苯基，C1-4烷氧基，卤素，硝基，C1-4酯基，R为在喹啉苯环或杂环上任意单取代。
2.如权利要求1所述的1,2,3,4-四氢喹啉类化合物的合成方法，其特征在于，所述溶剂为二氯甲烷或者甲苯；所述催化剂I2的加入量为喹啉摩尔量的20%；频哪醇硼烷的用量为喹啉化合物摩尔量的4倍。
CN201810856091.7A 2018-07-31 2018-07-31 一种合成1,2,3,4-四氢喹啉类化合物的方法 Pending CN108822030A (zh)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112266364A (zh) * 2020-10-23 2021-01-26 云南民族大学 一种四氢喹喔啉化合物的制备方法
CN114409691A (zh) * 2022-02-11 2022-04-29 安阳师范学院 一种苯并硅氧硼杂环化合物的制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHUN-HUA YANG ET AL.: "Iodine catalyzed reduction of quinolines under mild reaction conditions", 《CHEM. COMMUN.》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112266364A (zh) * 2020-10-23 2021-01-26 云南民族大学 一种四氢喹喔啉化合物的制备方法
CN112266364B (zh) * 2020-10-23 2023-11-17 云南民族大学 一种四氢喹喔啉化合物的制备方法
CN114409691A (zh) * 2022-02-11 2022-04-29 安阳师范学院 一种苯并硅氧硼杂环化合物的制备方法

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