摘要/Abstract

报道了可见光促进张力环烷醇氧化开环后实现喹喔啉酮的C(3)-酮烷基化反应. 室温下, 该反应以张力环醇为潜在的烷基化试剂, 过硫酸钾为氧化剂, 在甲醇与水的混合溶液中, 借助可见光照射实现. 通过该反应, 一系列带有羰基官能团的不同链长的烷基片段被成功地引入到各种取代的喹喔啉酮中, 为喹喔啉酮类化合物的修饰提供了更加绿色、环保和简洁的方法.
关键词: 喹喔啉酮, 环烷醇, 氧化开环, 烷基化, 可见光促进
Substituted quinoxalin-2(1H)-ones represent an important class of fused heterocyclic compounds which are existing in numerous bioactive natural products, pharmaceuticals, and functional materials. As a result, there are many methods for the synthesis of this heterocyclic compounds over the past several years. In this context, the direct C—H functionalization of quinoxalin-2(1H)-ones have proved to be an effective protocol to diverse heterocycles, such as radical C(3)—H arylation, phosphonation, amination, and acylation of quinoxalin-2(1H)-ones. However, the direct C—H alkylation of quinoxalin-2(1H)-ones is still rare. Because of their importance, it is desirable to introduce alkyl substituents, especially those bearing functional groups, at the 3-position of quinoxalin-2(1H)-ones, which would probably promote their applications in new drug discovery and development. Thus, this article reports a visible light promoted C(3)-ketoalkylation of quinoxaline-2(1H)-ones via oxidative ring-opening of cycloalkanols. At room temperature, the reaction is carried out by using cycloalkanols as the ketoalkylating agent and potassium persulfate as oxidizing agent in a solution of methanol and water (V∶V=1∶2) for 16 h upon visible light irradiation. A variety of keto-functionalized alkyl moieties with different chain length have been successfully incorporated into the C(3)-position of quinoxalin-2(1H)-ones. Thus, the procedure provides a greener, environmentally friendly and simple method for the synthesis of quinoxalin-2(1H)-one derivatives. A representative procedure for this reaction is given as follows. An oven-dried quartz reaction tube (10 mL) equipped with a magnetic stir bar was charged with K₂S₂O₈ (2.0 equiv., 0.4 mmol), quinoxalin-2(1H)-one 1 (1.0 equiv., 0.2 mmol) and cycloalkanol 2 (1.5 equiv., 0.3 mmol). Then, the tube was evacuated and backfilled with nitrogen (three times). Subsequently, a solution of 1.3 mL of H₂O and 0.7 mL of MeOH were added under nitrogen. Then the reaction tube was sealed and was irradiated under blue light at room temperature for 16 h. After completion of the reaction, ethyl acetate was added to the reaction mixture, and washed with brine (10 mL), dried over Na₂SO₄ and concentrated in vacuo. Purification of the crude product by flash chromatography on silica gel (petroleum ether/ethyl acetate, V∶V=4∶1) affords the corresponding product.
Key words: quinoxalin-2(1H)-one, cycloalkanol, oxidative ring-opening, ketoalkylation, visible light promoted


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