Rapid and Efficient Microwave‐Assisted Friedländer Quinoline Synthesis,ChemistryOpen

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Rapid and Efficient Microwave‐Assisted Friedländer Quinoline Synthesis
ChemistryOpen ( IF 2.5 ) Pub Date : 2020-11-05 , DOI: 10.1002/open.202000247
Helen V Bailey ₁ , Mary F Mahon ₂ , Nigel Vicker ₁ , Barry V L Potter _{1,

3}

Affiliation

A microwave‐based methodology facilitates reaction of 2‐aminophenylketones with cyclic ketones to form a quinoline scaffold. Syntheses of amido‐ and amino‐linked 17β‐hydroxysteroid dehydrogenase type 3 inhibitors with a benzophenone‐linked motif were pursued using 2‐aminobenzophenone as building block. Two amido‐linked targets were achieved in modest yield, but when using microwave‐assisted reductive amination for the amino‐linked counterparts an unexpected product was observed. X‐ray crystallography revealed it as a quinoline derivative, leading to optimisation of a simple and efficient modification of Friedländer methodology. Using reagents and acetic acid catalyst in organic solvent the unassisted reaction proceeds only over several days and in very poor yield. However, by employing neat acetic acid as both solvent and acid catalyst with microwave irradiation at 160 °C quinoline synthesis is achieved in 5 minutes in excellent yield. This has advantages over the previously reported high temperatures or strong acids required, not least given the green credentials of acetic acid, and examples using diverse ketones illustrate applicability. Additionally, he unassisted reaction proceeds effectively at room temperature, albeit much more slowly.

中文翻译：

快速高效的微波辅助弗里德兰德喹啉合成

基于微波的方法促进 2-氨基苯基酮与环酮反应形成喹啉支架。使用 2-氨基二苯甲酮作为结构单元合成具有二苯甲酮连接基序的酰胺和氨基连接的 17β-羟基类固醇脱氢酶 3 型抑制剂。两个酰胺连接的目标以适度的收率实现，但当使用微波辅助还原胺化氨基连接的对应物时，观察到了意想不到的产物。 X 射线晶体学显示其为喹啉衍生物，从而优化了 Friedländer 方法的简单而有效的修改。在有机溶剂中使用试剂和乙酸催化剂，无辅助反应仅进行几天且收率非常低。然而，通过使用纯乙酸作为溶剂和酸催化剂，并在 160 °C 的微波照射下，喹啉合成可在 5 分钟内实现，收率优异。这比之前报道的所需的高温或强酸具有优势，尤其是考虑到乙酸的绿色证书，并且使用不同酮的例子说明了适用性。此外，无辅助反应在室温下有效进行，尽管速度慢得多。

更新日期：2020-11-06

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