| Abstract | Cilj ovog rada bila je regioselektivna sinteza 4-fenil-1,2,3-triazolnih derivata benzimidazo[1,2-a]kinolina (3−6, 11, 12) kao spojeva s potencijalnim antitumorskim djelovanjem. U tu svrhu iz 5-klorbenzimidazo[1,2-a]kinolin-6-karbonitrila (1) i njegovih 2-kloriranih i 2-fluoriranih derivata (7, 9) sintetizirani su azidi benzimidazo[1,2-a]kinolin-6-karbonitrila 2, 8 i 10. 1,2,3-triazolni derivati benzimidazo[1,2-a]kinolina 3−6, 11 i 12 pripravljeni su reakcijom 1,3-dipolarne cikoladicije odgovarajućeg azida (2, 8, 10) i različitih terminalnih alkina uz Cu(I), kao katalizator, prema načelima ΄klik΄ kemije. Kako bi se dobilo što bolje iskorištenje ciljanih spojeva, kod sinteze spojeva 4, 5 i 6 korištena su dva sintetska puta. Prvi sintetski put uključuje reakciju prevođenja 5-klorbenzimidazo[1,2-a]kinolina-6-karbonitrila (1) u azid 2 i njegovu izolaciju te potom ΄klik΄ reakciju azida 2 i odgovarajućih alkina u 1,4-disupstituirane 1,2,3-triazolne derivate benzimidazo[1,2-a]kinolina (3−6). Drugi sintetski put bila je tandemska reakcija u kojoj se azid 2 nije izolirao nego je in situ reagirao s odgovarajućim terminalnim alkinima pri čemu su dobiveni 1,4-disupstituirani 1,2,3-triazolni derivati benzimidazo[1,2-a]kinolina 4, 5 i 6. Reakcije su provođene pri povišenoj temperaturi, a produkti reakcija su izolirani kolonskom kromatografijom. Strukture svih sintetiziranih spojeva potvrđene su spektroskopijom 1H i 13C NMR. |
| Abstract (english) | The aim of this work was the regioselective synthesis of novel 4-phenyl-1,2,3-triazolyl substituted benzimidazo[1,2-a]quinolines (3−6, 11, 12) with potential antitumor activity. For this purpose, 5-chlorobenzimidazo[1,2-a]quinoline-6-carbonitrile (1) and its 2-chloro and 2-fluoro derivatives (7, 9) were converted to the corresponding azido derivatives of benzimidazo[1,2-a]quinoline 2, 8 and 10. 1,2,3-Triazole derivatives of benzimidazo[1,2-a]quinoline 3−6, 11 and 12 were then prepared using 1,3-dipolar cycloaddition reaction of the corresponding azide derivative (2, 8, 10) and corresponding terminal alkynes with Cu(I), as a catalyst, following the concept of ´click´ chemistry. In order to obtain better overall yield of the target compounds, two synthetic pathways were used in the synthesis of compounds 4, 5 and 6. First pathway included the conversion of the 5-chlorobenzimidazo[1,2-a]quinoline-6-carbonitrile (1) to the azide 2, its isolation and then a ´click´ reaction of the azide 2 and the corresponding alkynes to form 1,4-disubstituted 1,2,3-triazole derivatives of benzimidazo[1,2-a]quinoline (3−6). Second synthetic pathway was a tandem reaction in which the azido derivative 2 was not isolated, but in situ reacted with the corresponding terminal alkynes to afford, 1,4-disubstituted 1,2,3-triazole derivatives of benzimidazo[1,2-a]quinoline 4, 5 and 6. The reactions were performed at reflux, and the reaction products were isolated by column chromatography. The structures of all compounds have been confirmed by 1H and 13C NMR spectroscopy. |
