CN110156673A - 二氯二茂锆催化制备喹啉类化合物的方法 - Google Patents
二氯二茂锆催化制备喹啉类化合物的方法 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
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- 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
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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
- C07D215/16—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
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
本发明公开了一种二氯二茂锆催化制备喹啉类化合物的方法，该方法以3‑丁炔‑2‑酮类化合物和邻氨基苯硫醇类化合物作为原料，以二氯二茂锆作为催化剂，以L‑苯丙氨酸、酪氨酸等作为催化剂配体，以N,N‑二甲基甲酰胺为溶剂，以单质碘、过氧化氢、过氧叔丁醇等作为氧化剂，可高效高产率制备喹啉类化合物。本发明所用催化剂用量少、廉价、对空气稳定，反应的条件温和，操作简单，反应结束后将产物萃取洗涤及简单的柱层析分离，即可得到喹啉类化合物，为喹啉类化合物的制备开启了低成本的高效途径，具有广阔的应用前景。
Description
技术领域
本发明属于喹啉类化合物的合成技术领域，具体涉及一种二氯二茂锆催化3-丁炔-2-酮类化合物和邻氨基苯硫醇类化合物反应，高效制备喹啉类化合物的方法。
背景技术
喹啉类化合物是一类广泛存在的生物碱类化合物，常用在医药、农药、染料等中，因其具有广泛的生物学和药理作用而受到人们的重视。喹啉药效基团有重要的功能，它被报道具有药理活性的多样性，如：抗癌、抗疟疾、抗结核、抗菌、抗炎、抗氧化剂、抗高血压、抗艾滋病、治疗红斑狼疮及神经退行性疾病等，在药物及有机合成中具有重要意义。
目前，合成喹啉类化合物的方法多种多样，用于催化的金属催化剂有Rh、Ru、Pt、Pd、Ir、Mo、Co、Bi、Ga、Sc、Hf、Fe、Ni、Au、Ag、Cu等，非金属催化剂有甲酸、高氯酸、硫酸、氢氧化钾等。然而，现有方法或多或少都有需要进一步完善的地方，如强酸强碱、高温高压、催化剂毒性大、合成步骤繁琐等，反应条件苛刻，成本较高，反应时间较长，因此，开发更多稳定、廉价、高效、条件温和的催化方法，对喹啉类化合物的制备具有重要意义。
发明内容
本发明所要解决的技术问题在于克服现有喹啉类化合物制备方法存在的缺点，提供一种操作简单、反应条件温和、高效制备喹啉类化合物的方法。
解决上述技术问题所采用的技术方案是：将式I所示3-丁炔-2-酮类化合物和式II所示邻氨基苯硫醇类化合物加入N,N-二甲基甲酰胺中，并加入二氯二茂锆和配体，在室温～40℃下搅拌反应4～6小时后，再加入氧化剂，继续反应1～3小时，分离纯化产物，得到式III所式喹啉类化合物；
式中R1和R2各自独立的代表芳基或取代芳基，具体如：苯基、C1～C4烷基取代苯基、C1～C4烷氧基取代苯基、卤代苯基、三氟甲基取代苯基、硝基取代苯基等；R3、R4、R5、R6各自独立的代表H、氟、氯、溴、C1～C4烷基、C1～C4烷氧基中任意一种。
上述的配体为L-苯丙氨酸、酪氨酸中任意一种，优选L-苯丙氨酸。
上述的氧化剂为单质碘、双氧水、过氧叔丁醇中任意一种，优选单质碘。
上述制备方法中，优选所述3-丁炔-2-酮类化合物与邻氨基苯硫醇类化合物的摩尔比为1:1～1.5。
上述制备方法中，优选所述二氯二茂锆的加入量是3-丁炔-2-酮类化合物摩尔量的4％～6％。
上述制备方法中，优选所述配体的加入量是3-丁炔-2-酮类化合物摩尔量的8％～12％。
上述制备方法中，优选所述氧化剂的加入量是3-丁炔-2-酮类化合物摩尔量的1.1～1.5倍。
本发明以N,N-二甲基甲酰胺为溶剂，以二氯二茂锆为催化剂，以L-苯丙氨酸或酪氨酸为配体，以单质碘、双氧水或过氧叔丁醇为氧化剂，高效催化3-丁炔-2-酮类化合物和邻氨基苯硫醇类化合物直接反应得到喹啉类化合物。本发明所用催化剂用量少、廉价、无毒、对空气稳定，反应条件温和，操作简单，反应结束后将产物柱层析分离即可得到具有广泛的生物活性和药用价值的喹啉类化合物，为喹啉类化合物的制备开辟了新的低成本操作简单的高效途径，具有广阔的应用前景。
具体实施方式
下面结合实施例对本发明进一步详细说明，但本发明的保护范围不仅限于这些实施例。
实施例1
制备结构式如下的2,4-二苯基喹啉
向反应瓶中加入0.103g(0.5mmol)1,4-二苯基-3-丁炔-2-酮、0.0073g(0.025mmol)二氯二茂锆、0.0082g(0.05mmol)L-苯丙氨酸、64μL(0.6mmol)邻氨基苯硫醇、1mL DMF，在30℃下搅拌反应5小时，再加入0.1518g(0.6mmol)碘，继续在30℃下搅拌反应2小时，停止反应，加入10mL饱和硫代硫酸钠水溶液，加入10mL乙酸乙酯萃取3次，将有机相旋转蒸发除去乙酸乙酯，用硅胶柱分离(洗脱剂是石油醚与二氯甲烷的体积比为2:1的混合液)，得到2,4-二苯基喹啉，其产率为93％，产物的波谱数据为：1H NMR(400MHz,CDCl3)δ8.16(d,J＝8.4Hz,1H),8.10(d,J＝7.4Hz,2H),7.81(d,J＝8.3Hz,1H),7.72(s,1H),7.63(t,J＝7.5Hz,1H),7.45(d,J＝5.4Hz,4H),7.42(d,J＝7.2Hz,3H),7.40-7.36(m,2H)；13C NMR(101MHz,CDCl3)δ156.91,149.18,148.86,139.70,138.45,130.17,129.59,129.53,129.36,128.86,128.62,128.42,127.61,126.35,125.80,125.66,119.37.
对比例1
在实施例1中，所用的DMF用等体积的乙醇替换，其它步骤与实施例1相同，得到2,4-二苯基喹啉，其产率为17％。
对比例2
在实施例1中，所用的L-苯丙氨酸用等摩尔量的5-磺基水杨酸替换，其它步骤与实施例1相同，得到2,4-二苯基喹啉，其产率为24％。
实施例2
制备结构式如下的2-(4-氯苯基)-4-苯基喹啉
本实施例中，用等摩尔的1-(4-氯苯基)-4-苯基-3-丁炔-2-酮替换实施例1中所用的1,4-二苯基-3-丁炔-2-酮，其它步骤与实施例1相同，得到2-(4-氯苯基)-4-苯基喹啉，其产率为84％，产物的波谱数据为：1H NMR(400MHz,CDCl3)δ8.12(d,J＝8.4Hz,1H),8.05(d,J＝8.4Hz,2H),7.80(d,J＝8.3Hz,1H),7.68-7.60(m,2H),7.44(s,5H),7.38(d,J＝8.2Hz,3H)；13C NMR(101MHz,CDCl3)δ155.51,149.41,148.78,138.27,138.03,135.58,130.11,129.70,129.55,129.01,128.84,128.65,128.51,126.55,125.84,125.69,118.89.
实施例3
制备结构式如下的2-(4-氟苯基)-4-苯基喹啉
本实施例中，用等摩尔的1-(4-氟苯基)-4-苯基-3-丁炔-2-酮替换实施例1中所用的1,4-二苯基-3-丁炔-2-酮，其它步骤与实施例1相同，得到2-(4-氟苯基)-4-苯基喹啉，其产率为90％，产物的波谱数据为：1H NMR(400MHz,CDCl3)δ8.16-8.06(m,3H),7.83-7.77(m,1H),7.69-7.60(m,2H),7.49-7.40(m,5H),7.38(ddd,J＝8.2,6.8,1.3Hz,1H),7.11(t,J＝8.7Hz,2H)；13C NMR(101MHz,CDCl3)δ165.07,162.59,155.76,149.35,148.77,138.32,135.81,135.77,130.04,129.66,129.55,129.48,129.39,128.63,128.48,126.40,125.70,125.68,118.98,115.88,115.67.
实施例4
制备结构式如下的2-(4-溴苯基)-4-苯基喹啉
本实施例中，用等摩尔的1-(4-溴苯基)-4-苯基-3-丁炔-2-酮替换实施例1中所用的1,4-二苯基-3-丁炔-2-酮，其它步骤与实施例1相同，得到2-(4-溴苯基)-4-苯基喹啉，其产率为80％，产物的波谱数据为：1H NMR(400MHz,CDCl3)δ8.12(d,J＝8.4Hz,1H),7.97(d,J＝8.3Hz,2H),7.79(d,J＝8.3Hz,1H),7.66(s,1H),7.62(t,J＝7.9Hz,1H),7.53(d,J＝8.3Hz,2H),7.41(d,J＝18.8Hz,5H),7.36(d,J＝7.5Hz,1H)；13C NMR(101MHz,CDCl3)δ154.45,148.34,147.71,137.39,137.17,130.88,129.04,128.63,128.47,128.03,127.57,127.44,125.50,124.78,124.62,122.89,117.75.
实施例5
制备结构式如下的2-(4-甲基苯基)-4-苯基喹啉
本实施例中，用等摩尔的1-(4-甲基苯基)-4-苯基-3-丁炔-2-酮替换实施例1中所用的1,4-二苯基-3-丁炔-2-酮，其它步骤与实施例1相同，得到2-(4-甲基苯基)-4-苯基喹啉，其产率为84％，产物的波谱数据为：1H NMR(400MHz,CDCl3)δ8.10(d,J＝8.5Hz,1H),7.96(d,J＝8.2Hz,2H),7.73(dd,J＝8.4,1.4Hz,1H),7.64(s,1H),7.54(ddd,J＝8.2,6.8,1.5Hz,1H),7.41-7.30(m,5H),7.27(ddd,J＝8.3,6.8,1.3Hz,1H),7.16(d,J＝7.9Hz,2H),2.26(s,3H)；13C NMR(101MHz,CDCl3)δ156.87,149.07,148.91,139.47,138.55,136.89,130.14,129.64,129.51,128.64,128.42,127.53,126.20,125.76,125.68,119.23,21.44.
实施例6
制备结构式如下的2-苯基-4-(4-氯苯基)喹啉
本实施例中，用等摩尔的1-苯基-4-(4-氯苯基)-3-丁炔-2-酮替换实施例1中所用的1,4-二苯基-3-丁炔-2-酮，其它步骤与实施例1相同，得到2-苯基-4-(4-氯苯基)喹啉，其产率为85％，产物的波谱数据为：1H NMR(400MHz,CDCl3)δ8.09(d,J＝8.4Hz,1H),8.02(d,J＝7.5Hz,2H),7.66(d,J＝8.4Hz,1H),7.59(s,1H),7.55(t,J＝7.6Hz,1H),7.34(d,J＝9.0Hz,4H),7.31-7.26(m,4H)；13C NMR(101MHz,CDCl3)δ155.68,147.68,146.67,138.30,135.63,133.48,129.74,129.12,128.53,128.33,127.73,126.43,125.41,124.35,124.10,118.07.
实施例7
制备结构式如下的2-(4-氯苯基)-4-苯基喹啉
本实施例中，用等摩尔的2-氨基4-氯苯硫醇替换实施例1中所用的邻氨基苯硫醇，其它步骤与实施例1相同，得到2-(4-氯苯基)-4-苯基喹啉，其产率为81％，产物的波谱数据为：1H NMR(400MHz,CDCl3)δ8.14(d,J＝1.8Hz,1H),8.08(d,J＝7.1Hz,2H),7.73(d,J＝9.0Hz,1H),7.70(s,1H),7.46-7.40(m,7H),7.38(d,J＝7.0Hz,1H),7.30(dd,J＝8.9,2.0Hz,1H)；13C NMR(101MHz,CDCl3)δ157.85,149.32,149.22,139.17,137.94,135.45,129.69,129.49,128.99,128.89,128.74,128.70,128.68,127.61,127.20,127.06,124.24,119.40.
实施例8
本实施例中，用等摩尔的过氧化氢替换实施例1中所用的单质碘，其它步骤与实施例1相同，得到2,4-二苯基喹啉，其产率为71％。
实施例9
本实施例中，用等摩尔的过氧叔丁醇替换实施例1中所用的单质碘，其它步骤与实施例1相同，得到2,4-二苯基喹啉，其产率为85％。
实施例10
本实施例中，用等摩尔的酪氨酸替换实施例1中所用的L-苯丙氨酸，其它步骤与实施例1相同，得到2,4-二苯基喹啉，其产率为80％。
Claims (8)
1.一种二氯二茂锆催化制备喹啉类化合物的方法，其特征在于：将式I所示3-丁炔-2-酮类化合物和式II所示邻氨基苯硫醇类化合物加入N,N-二甲基甲酰胺中，并加入二氯二茂锆和配体，在室温～40℃下搅拌反应4～6小时后，再加入氧化剂，继续反应1～3小时，分离纯化产物，得到式III所式喹啉类化合物；
式中R1和R2各自独立的代表芳基或取代芳基；R3、R4、R5、R6各自独立的代表H、氟、氯、溴、C1～C4烷基、C1～C4烷氧基中任意一种；
上述的配体为L-苯丙氨酸、酪氨酸中任意一种；
上述的氧化剂为单质碘、双氧水、过氧叔丁醇中任意一种。
2.根据权利要求1所述的二氯二茂锆催化制备喹啉类化合物的方法，其特征在于：所述的R1和R2各自独立的代表苯基、C1～C4烷基取代苯基、C1～C4烷氧基取代苯基、卤代苯基、三氟甲基取代苯基、硝基取代苯基中任意一种。
3.根据权利要求1或2所述的二氯二茂锆催化制备喹啉类化合物的方法，其特征在于：所述的配体为L-苯丙氨酸。
4.根据权利要求1或2所述的二氯二茂锆催化制备喹啉类化合物的方法，其特征在于：所述的氧化剂为单质碘。
5.根据权利要求1或2所述的二氯二茂锆催化制备喹啉类化合物的方法，其特征在于：所述3-丁炔-2-酮类化合物与邻氨基苯硫醇类化合物的摩尔比为1:1～1.5。
6.根据权利要求1或2所述的二氯二茂锆催化制备喹啉类化合物的方法，其特征在于：所述二氯二茂锆的加入量是3-丁炔-2-酮类化合物摩尔量的4％～6％。
7.根据权利要求1或2所述的二氯二茂锆催化制备喹啉类化合物的方法，其特征在于：所述配体的加入量是3-丁炔-2-酮类化合物摩尔量的8％～12％。
8.根据权利要求1或2所述的二氯二茂锆催化制备喹啉类化合物的方法，其特征在于：所述氧化剂的加入量是3-丁炔-2-酮类化合物摩尔量的1.1～1.5倍。
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110724094A (zh) * | 2019-10-29 | 2020-01-24 | 陕西科技大学 | 一种喹啉类化合物及其合成方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105461624A (zh) * | 2016-01-04 | 2016-04-06 | 陕西师范大学 | 一种磺基苯甲酸协同二氯二茂钛水相高效制备喹啉衍生物的方法 |
| CN106187885A (zh) * | 2016-07-25 | 2016-12-07 | 陕西师范大学 | 一种氧化铜协同茂锆双酸体系高效制备多取代喹啉的方法 |
| CN111848508A (zh) * | 2020-07-31 | 2020-10-30 | 宁波大学 | 一种制备喹啉化合物的方法 |
| CN113277978A (zh) * | 2021-06-02 | 2021-08-20 | 河南师范大学 | 一种2，4-双取代喹啉类化合物的制备方法 |
-
2019
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105461624A (zh) * | 2016-01-04 | 2016-04-06 | 陕西师范大学 | 一种磺基苯甲酸协同二氯二茂钛水相高效制备喹啉衍生物的方法 |
| CN106187885A (zh) * | 2016-07-25 | 2016-12-07 | 陕西师范大学 | 一种氧化铜协同茂锆双酸体系高效制备多取代喹啉的方法 |
| CN111848508A (zh) * | 2020-07-31 | 2020-10-30 | 宁波大学 | 一种制备喹啉化合物的方法 |
| CN113277978A (zh) * | 2021-06-02 | 2021-08-20 | 河南师范大学 | 一种2，4-双取代喹啉类化合物的制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| GEMMA CABARROCAS等: ""Synthesis of novel optically pure quinolyl-β-amino alcohol derivatives from 2-amino thiophenol and chiral α-acetylenic ketones and their IBX-mediated oxidative cleavage to N-Boc quinolyl carboxamides"", 《TETRAHEDRON: ASYMMETRY》 * |
| T. MASQUELIN等: ""A novel access to 2,4-substituted quinolines from acetylenic ketones"", 《TETRAHEDRON》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110724094A (zh) * | 2019-10-29 | 2020-01-24 | 陕西科技大学 | 一种喹啉类化合物及其合成方法 |
| CN110724094B (zh) * | 2019-10-29 | 2022-06-14 | 陕西科技大学 | 一种喹啉类化合物及其合成方法 |
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