CN104892492A - 一种茚衍生物1-吡啶基-6-甲基茚及其合成方法 - Google Patents

一种茚衍生物1-吡啶基-6-甲基茚及其合成方法 Download PDF

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CN104892492A
CN104892492A CN201510339139.3A CN201510339139A CN104892492A CN 104892492 A CN104892492 A CN 104892492A CN 201510339139 A CN201510339139 A CN 201510339139A CN 104892492 A CN104892492 A CN 104892492A
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pyridyl
ethyl acetate
synthetic method
methyl indenes
reaction
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马培培
赵连敏
陆城业
陈大发
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Harbin Institute of Technology
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Harbin Institute of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/127—Preparation from compounds containing pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring

Abstract

本发明公开了一种茚衍生物1-吡啶基-6-甲基茚及其合成方法，所述方法为：在N2保护下，向三口瓶中加入2-溴吡啶、四氢呋喃，滴加正丁基锂，低温搅拌1h；将6-甲基-1-茚酮溶于四氢呋喃，慢慢滴加到反应中，低温反应2h，然后室温反应1h；加水淬灭反应后处理分离产物，得黄色油状液体；向该物质中加入浓硫酸，反应2h；氢氧化钠调节pH值至中性，乙酸乙酯萃取二～四次；合并有机层，无水硫酸钠干燥后将有机溶剂旋干，过一段硅胶柱，得黄色油状液体。本发明利用廉价的2-溴吡啶、茚酮和正丁基锂为原料制备1-吡啶基-6-甲基茚，便于后续在茚的2-号位引入不同的基团，合成茚环上带有不同取代基的茚衍生物，从而构筑具有不同空间构型的晶态网络配合物。

Description

一种茚衍生物1-吡啶基-6-甲基茚及其合成方法
技术领域
本发明涉及一种茚衍生物及其合成方法，具体涉及一种新型茚衍生物1-吡啶基-6-甲基茚及其合成方法。
背景技术
茚衍生物是一种常见的芳香化合物，广泛存在于天然产物、合成药物、染料、农药及日用化学品当中。在配位化学和金属有机化学中，茚衍生物能与多种金属配位，形成各种不同的配合物，对催化反应和计量反应都有十分重要的意义，促进配位化学和金属有机化学的发展。茚衍生物也被用于功能材料、特性表面的制备，以及超分子、高分子聚合物的合成等新兴领域。有些茚衍生物是一些具有特定生物活性的天然产物，如维生素B6、尼古丁、辅酶、生物碱等结构中的重要组成部分都含有茚衍生物。茚衍生物在药物化学中占有重要地位，大量具有特殊功效的茚衍生物类药物被合成，发挥着消炎平喘、抗抑郁、治疗高血压或低血压、抑制HIV蛋白酶再生、阻止或减少细胞凋亡等药性；在航空方面，茚衍生物可用作航空燃料的防震剂。因此，探究茚衍生物类化合物的合成工艺是十分具有应用价值和研究价值的。
侧链含有吡啶基团的茚类化合物无论在天然产物合成还是金属有机化学领域均具有重要意义，通过在茚环上引入各种不同的取代基团，有利于制备各种金属有机催化剂或各种含有茚基的高效药物。
发明内容
本发明的目的是提供一种茚衍生物1-吡啶基-6-甲基茚及其合成方法，该方法合成了一种新型的茚基吡啶，便于后续在茚的2-号位引入不同的基团，合成茚环上带有不同取代基的茚衍生物，丰富茚衍生物，从而构筑具有不同空间构型的晶态网络配合物。
本发明的目的是通过以下技术方案实现的：
一种茚衍生物1-吡啶基-6-甲基茚，其分子结构式如下：
。
上述茚衍生物1-吡啶基-6-甲基茚的合成方法，利用廉价的2-溴吡啶、茚酮、正丁基锂为原料，具体合成步骤如下：
一、在N2保护下，向三口瓶中加入9.64 g (61 mmol) 2-溴吡啶，加入50 mL四氢呋喃作为溶剂，-78 ℃滴加25 mL (61 mmol, 2.5 mol/L)正丁基锂，搅拌1 h，将7.16 g (49 mmol) 6-甲基-1-茚酮溶于40 mL四氢呋喃，-30 ~ -60 ℃低温环境慢慢滴加到反应中，-30 ~ -60 ℃反应2 h，然后室温反应1 h；加水淬灭反应，乙酸乙酯萃取二～四次；合并有机层，用无水硫酸钠干燥或氯化钙干燥后将有机溶剂旋干，过一段硅胶柱，以乙酸乙酯/石油醚=1/20（v/v）的混合液为洗脱液，得黄色油状液体。
二、向单口瓶中加入上述所得的黄色油状液体，向该物质中加入20 mL 85%的浓硫酸，反应2 h；氢氧化钠调节pH值至中性，乙酸乙酯萃取二～四次；合并有机层，用无水硫酸钠干燥或氯化钙干燥后将有机溶剂旋干，过一段硅胶柱，以乙酸乙酯/石油醚=1/10（v/v）的混合液为洗脱液，得黄色油状液体，即为1-吡啶基-6-甲基茚。
本发明具有如下优点：
（1）反应操作简单，总体反应步骤少，反应时间短，产率高。
（2）反应原料廉价易得，反应成本低。
（3）反应相对专一，副反应少，且该化合物的具体合成工艺为首次报道；
（4）本发明利用廉价的2-溴吡啶、茚酮和正丁基锂为原料制备1-吡啶基-6-甲基茚，便于后续在茚的2-号位引入不同的基团，合成茚环上带有不同取代基的茚衍生物，从而构筑具有不同空间构型的晶态网络配合物。
附图说明
图1为本发明合成的1-吡啶基-6-甲基茚的核磁氢谱共振图谱；
图2为本发明合成的1-吡啶基-6-甲基茚的核磁碳谱共振图谱。
具体实施方式
下面结合附图对本发明的技术方案作进一步的说明，但并不局限于此，凡是对本发明技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，均应涵盖在本发明的保护范围中。
本发明提供了一种1-吡啶基-6-甲基茚的合成方法，具体合成步骤如下：
在N2保护下，向三口瓶中加入9.64 g (61 mmol) 2-溴吡啶，加入50 mL四氢呋喃作为溶剂，-78 ℃滴加25 mL (61 mmol, 2.5 mol/L)正丁基锂，搅拌1 h，将7.16 g (49 mmol) 6-甲基-1-茚酮溶于40 mL四氢呋喃，-30 ~ -60 ℃低温环境慢慢滴加到反应中，低温反应2 h，然后室温反应1 h；加水淬灭反应，乙酸乙酯萃取三次；合并有机层，无水硫酸钠干燥后将有机溶剂旋干，过一段硅胶柱，以乙酸乙酯/石油醚=1/20（v/v）的混合液为洗脱液，得黄色油状液体。向单口瓶中加入上述所得的黄色油状液体，向该物质中加入20 mL 85%的浓硫酸，反应2 h；氢氧化钠调节pH值至中性，乙酸乙酯萃取三次；合并有机层，无水硫酸钠干燥后将有机溶剂旋干，过一段硅胶柱，以乙酸乙酯/石油醚=1/10（v/v）的混合液为洗脱液，得黄色油状液体，即为1-吡啶基-6-甲基茚。（5.68 g, 56%）。如图1所示，1H NMR (400 MHz, CDCl3, ppm) δ 8.79 (m, 1H), δ 8.07 (s, 1H), δ 7.68 (m, 2H), δ 7.45 (d, J = 7.6 Hz, 1H), δ 7.21 (m, 1H), δ 7.15 (d, J = 7.6 Hz, 1H), δ 6.96 (t, J = 2.2 Hz, 1H), δ 3.52 (d, J = 1.8 Hz, 2H), δ 2.52 (s, 3H)。如图2所示，13C NMR (100 MHz, CDCl3, ppm) δ 154.80, 148.97, 143.74, 142.77, 141.38, 135.91, 135.43, 133.69, 125.61, 123.20, 122.41, 121.702, 121.658, 37.53, 21.39. HRMS (ESI) m/z (%; MeOH solvent) : calcd for [M+H+] 208.1126; found: 208.1125。

Claims (6)

1.一种茚衍生物1-吡啶基-6-甲基茚，其特征在于所述1-吡啶基-6-甲基茚的分子结构式如下：
。
2.一种权利要求1所述的茚衍生物1-吡啶基-6-甲基茚的合成方法，其特征在于所述合成方法步骤如下：
一、在N2保护下，向三口瓶中加入61 mmol 2-溴吡啶，加入50 mL四氢呋喃作为溶剂，-78 ℃滴加25 mL正丁基锂，搅拌1 h，将49 mmol 6-甲基-1-茚酮溶于40 mL四氢呋喃，-30 ~ -60 ℃低温环境慢慢滴加到反应中，-30 ~ -60 ℃反应2 h，然后室温反应1 h；加水淬灭反应，乙酸乙酯萃取二～四次；合并有机层，用无水硫酸钠干燥或氯化钙干燥后将有机溶剂旋干，过一段硅胶柱，以乙酸乙酯/石油醚的混合液为洗脱液，得黄色油状液体；
二、向单口瓶中加入上述所得的黄色油状液体，向该物质中加入20 mL浓硫酸，反应2 h；氢氧化钠调节pH值至中性，乙酸乙酯萃取二～四次；合并有机层，用无水硫酸钠干燥或氯化钙干燥后将有机溶剂旋干，过一段硅胶柱，以乙酸乙酯/石油醚的混合液为洗脱液，得黄色油状液体，即为1-吡啶基-6-甲基茚。
3.根据权利要求2所述的1-吡啶基-6-甲基茚的合成方法，其特征在于所述正丁基锂的浓度为2.5 mol/L。
4.根据权利要求2所述的1-吡啶基-6-甲基茚的合成方法，其特征在于所述步骤一中，石油醚和乙酸乙酯的体积比为20:1。
5.根据权利要求2所述的1-吡啶基-6-甲基茚的合成方法，其特征在于所述步骤二中，石油醚和乙酸乙酯的体积比为10:1。
6.根据权利要求2所述的1-吡啶基-6-甲基茚的合成方法，其特征在于所述浓硫酸的浓度为85%。
CN201510339139.3A 2015-06-18 2015-06-18 一种茚衍生物1-吡啶基-6-甲基茚及其合成方法 Pending CN104892492A (zh)

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WO2014046134A1 (ja) * 2012-09-18 2014-03-27 出光興産株式会社 官能化α－オレフィン重合体、それを用いた硬化性組成物及び硬化物
WO2014096151A2 (en) * 2012-12-19 2014-06-26 H. Lundbeck A/S 6-chloro-3-(phenyl-d5)-inden-1-one and use thereof
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