N-芳基(烷基)-9-苯基-吡咯并[3,4-b]喹啉-1-酮衍生物的合成

Synthesis of N-aryl(alkyl)-9-phenyl-pyrrolo[3,4-b]quinoline-1-one derivatives

吡咯并喹啉酮结构的化合物作为一类重要杂环化合物被广泛研究,它具有一定的生物活性,它可作为乙酰胆碱酯酶抑制剂,它有抗肿瘤活性.然而该类杂环化合物传统的合成方法尚存在合成和处理方法较为复杂,或使用有毒有害的有机溶剂以及碱性催化剂等问题.本合成方法简捷,无需用到催化剂,仅用无水乙醇和冰乙酸作为溶剂,以2-氯甲基-4-苯基-3-喹啉甲酸乙酯(1)为底物与胺类化合物2a-l在EtOH-AcOH(V/V,10:1)溶剂体系中回流反应经Williamson反应形成C-N键然后经分子内环化得到一系列吡咯并[3,4-b]喹啉-1-酮衍生物,即N-芳基(烷基)-9-苯基-2,3-二氢-1H-吡咯并[3,4-b]喹啉-1-酮衍生物3al.该类化合物的结构经IR、~1H NMR、^(13)C NMR、HRMS等方法表征并得以确认.

Pyrrolo[3,4-b]quinoline-1-ones represent an important class of heterocycles and have been claimed to exhibite potent antitumor and acetylcholinesterase inhibitory activities.The reported synthetic methods have some disadvantages such as the use of toxic and harmful solvent and catalyst and tedious workup.As such,we present hevein a facile and efficient catalyst-free protocol for the synthesis of a series of pyrrolo[3,4-b]quinoline-1-ones,namely N-aryl(alkyl)-9-phenyl-2,3-dihydro-1 H-pyrrolo[3,4-b]quinoline-1-ones 3 a-l has been achieved via a two-step procedure,involving a cascade Williamson-type condensation reaction of ethyl 2-(chloromethyl)-4-phenylquinoline-3-carboxylate(1) with various amines 2 a-l and subsequent intramolecular C-N bond cyclization of the resulting intermediates in refluxing Et OH-Ac OH(V/V,10: 1) solvent system in a single synthetic operation.The structures of all the newly-synthesized compounds were characterized by IR,~1H NMR,^(13)C NMR and HRMS.