Acta Chimica Sinica ›› 2019, Vol. 77 ›› Issue (9): 895-900.DOI: 10.6023/A19040155 Previous Articles     Next Articles

Special Issue: 有机自由基化学



海曼a, 郭丽娜a, 王乐b, 段新华a*()   

  1. a西安交通大学理学院化学系 教育部物质非平衡合成与调控重点实验室 西安 710049
    b宝鸡文理学院化学化工学院化学系 宝鸡 721013
  • 投稿日期:2019-04-30 发布日期:2019-05-21
  • 通讯作者: 段新华
  • 基金资助:
    项目受陕西省自然科学基金资助(No. 2019JM-299)

Visible Light Promoted Ketoalkylation of Quinoxaline-2(1H)-ones via Oxidative Ring-Opening of Cycloalkanols

Hai, Mana, Guo, Li-Naa, Wang, Leb, Duan, Xin-Huaa*()   

  1. aDepartment of Chemistry, School of Science, and MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi’an Jiaotong University, Xi’an 710049
    bShaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji 721013
  • Received:2019-04-30 Published:2019-05-21
  • Contact: Duan, Xin-Hua
  • Supported by:
    Project supported by the Natural Science Foundation in Shaanxi Province(No. 2019JM-299)

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 (VV=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, VV=4∶1) affords the corresponding product.

Key words: quinoxalin-2(1H)-one, cycloalkanol, oxidative ring-opening, ketoalkylation, visible light promoted