Practical Synthesis of 4-Chloro-2-(2-naphthyl)quinoline, a Precursor to Triple-Helix DNA Intercalators

Abstract

Several synthetic approaches to the title compound and analogs have been evaluated. This compound is a practical precursor to N-substituted 2-(2-naphthyl)quinolin-4-amines, the triplehelix DNA specific intercalators.

Synthesis and Activity of Substituted 2-Phenylquinolin-4-amines, Antagonists of Immunostimulatory CpG-Oligodeoxynucleotides

“…Note: For the sake of clarity of the presentation, all intermediate compounds are labeled with Roman numbers, as opposed to Arabic numbers assigned to quinoline products used for SAR analyses. The construction of a quinoline ring system was conducted by using chemistry , developed by us previously (Scheme ). Briefly, t -BuOK mediated cyclization of ketimines I − IV derived from 2-(trifluoromethyl)aniline and an aryl methyl ketone followed by one-pot hydrolysis of the resultant 4- tert -butoxyquinolines furnished the corresponding 4-hydroxyquinolines V − VIII .…”

“…2-Aryl-4-hydroxyquinolines V, VI, and VIII. These compounds were obtained by using a general procedure 17 and crystallized from MeOH. Compound, yield, mp: V, 38%, 179-181 °C; VI, 40%, 288-290 °C; VIII, 40%, 298-300 °C.…”

“…The reactions of V-VI-II with PCl 5/POCl3 were conducted by using a general procedure. 17 The products were crystallized from hexanes. Compound, yield, mp: IX, 85%, 74-76 °C; X, 88%, 68-70 °C; XI, 78%, 90-92 °C; XII, 84%, 84-85 °C.…”

Synthesis of quinolines and acridines by the reaction of 2-(perfluoroalkyl)anilines with lithium and Grignard reagents

“…It is the adduct 10 that undergoes intramolecular 6π-electron cyclization, as evidenced by the isolation and characterization of intermediate 4,4-disubstituted-3,4-dihydroquinoline [30]. The two methodologies discussed above are quite general in scope, and a large array of other substituted quinolines [29,[32][33][34][35][36][37][38] and fused quinolines including acridines [39,40] can easily be prepared by the reaction of 2 or 7 with various basic/nucleophilic reagents [41][42][43][44][45].…”

TMSBr-Promoted Cascade Cyclization of ortho-Propynol Phenyl Azides for the Synthesis of 4-Bromo Quinolines and Its Applications

“…Consequently, developing general and flexible approach towards these heterocycles has attracted much attention among synthetic chemists. Until now, despite significant achievements having been made in the construction of functionalized quinolines [14,15,16,17,18,19,20,21,22], methods for the direct synthesis of 4-halo quinolines are still limited [23,24,25,26]. 4-halo quinolines have been widely used as key synthetic intermediates for the construction of various bioactive molecules or drugs [27,28,29].…”