As a privileged fragment, quinoline is a ubiquitous subunit in many quinoline-containing natural products with remarkable biological activities. [1][2][3][4][5][6] Members of this family have wide applications in medicinal chemistry, being used as antimalarial, antiinflammatory agents, antiasthamatic, antibacterial, antihypertensive, and tyrosine kinase inhibiting agents. [1][2][3][4][5][6] In addition, quinolines are valuable synthons used for the preparation of nano-and meso-structures with enhanced electronic and photonic properties.7-9) Consequently, various procedures such as the Skraup, Doebner-Von Miller, Friedländer and Combes methods have been developed for the synthesis of quinoline derivatives. [10][11][12][13][14][15][16][17] Among them, the Friedländer annulation 14) is still one of the most simple and straightforward approaches for the synthesis of polysubstituted quinolines. The Friedländer quinoline synthesis consists of the reaction between a 2-aminoaryl ketones or aldehydes with a-methylene ketones under acid catalysts. Brønsted acids like hydrochloric acid, sulfuric acid, p-toluene sulfonic acid and phosphoric acid were widely used as catalysts. [18][19][20][21] Recently, Lewis acids such as ZnCl 2 , SnCl 2 , silver phosphotungstate, sodium fluoride, Neodymium(III) Nitrate Hexahydrate, CeCl 3 · 7H 2 O and AuCl 3 have been reported to be effective for the synthesis of quinolines. [22][23][24][25][26][27][28][29][30][31] However, many of these procedures suffered from harsh reaction conditions, low yields, difficulties in work up, and the use of stoichiometric and/or relatively expensive reagents.In continuation of our efforts to develop new methods in the synthesis of quinolines, 32-34) herein, we wish to report a mild and efficient approach for the synthesis of polysubstituted quinolines via Friedländer annulation using a catalytic amount of cuprous triflate (Cu(OTf) 2 ) under solvent-free conditions at room temperature. Accordingly, treatment of 2-aminoaryl ketones 1 with a-methylene ketones 2 in the presence of 20 mol% of Cu(OTf) 2 resulted in the formation of quinolines 3 in high yields (Chart 1).
ExperimentalA mixture of 2-aminoaryl ketone (1 mmol), a-methylene ketone (1.2 mmol) and Cu(OTf) 2 (0.2 mmol, 20 mol%) was stirred at room temperature for acyclic ketone and 60°C for cyclic ketone under solvent-free conditions for the appropriate time (Table 1). After completion of the reaction, as indicated by TLC, was added 10 ml of water to the reaction mixture and the product was filtrated and washed with water (2ϫ10 ml), and the solid product was recrystallized from ethanol to afford the pure product.All the products are known compounds, which were characterized by IR and 1 H-NMR spectral data and their mp's compared with literature reports.
32-37)
Results and DiscussionTo demonstrate the generality of this method, we next investigated the scope of this reaction and the results are sum- A mild and efficient route for the synthesis of quinolines utilizing cuprous triflate (Cu(OTf) 2 ) as a nove...
