Synthesis of aryl-substituted quinolines and tetrahydroquinolines through Suzuki–Miyaura coupling reactions

Abstract

The synthesis and characterization of substituted (trifluoromethoxy, thiomethyl, and methoxy) phenyl quinolines is described. Dichlorobis(triphenylphosphine)palladium(II)-catalyzed Suzuki–Miyaura cross-coupling of 6-bromo- and 6,8-dibromo-1,2,3,4-tetrahydroquinolines, 5-bromo-8-methoxyquinoline, and 5,7-dibromo-8-methoxyquinoline with substituted phenylboronic acids affords the corresponding 6-aryl- (13a–d), 6,8-diaryl- (14a–c), 5-aryl- (15), and 5,7-diaryl- (16b, c) tetrahydroquinolines and quinolines in high yields (68%–82%). The structures of all the products are characterized by 1H NMR, 13C NMR,19F NMR, and Fourier transform infrared spectroscopy and by elemental analysis.

Quinoline‐based promising anticancer and antibacterial agents, and some metabolic enzyme inhibitors

“…(3) and 6,8-dibromoquinoline (4) treated with NaOMe or CuCN were synthesized according to our reported procedures. [14,39] Furthermore, the synthesis of 5,7-dibromo-8-hydroxyquinoline (17) and 5,7-dibromo-8-methoxyquinoline (19) via bromination of 8hydroxyquinoline (15) and 8-methoxyquinoline (16), respectively, was reported in our recent works. [40,55] The isolated compounds, 2-10, 12-14, and 17-19, were fully characterized by melting point, HRMS analysis, infrared, 1 H, 13 C, HMBC (heteronuclear multiple bond correlation), and HETCOR spectroscopy in these papers.…”

“…[13][14][15] Many studies about pharmacological features of aryl or nitro/ amino-substituted quinolines have been interested due to that they have been starting materials for bioactive polycyclic systems. [16,17] Nitrated derivatives, which exhibit biological potency, that is, antileishmanial [18] or potent mutagenic activities, [19] are important key compounds for the preparation of amino derivatives for pharmacological use. [16,20] The aryl-substituted quinolines displayed a high antipesticide activity against the nematode Haemonchus contortus, [21] agricultural predatory activity, significant antibacterial activity, [22] anti-inflammatory, analgesic, antipyretic activities, and efficient inhibition of the COX-2 enzyme.…”

“…[39] Previously, brominated quinolines, the starting compounds, were synthesized according to reported procedures starting from 1,2,3,4tetrahydroquinoline and 8-hydroxyquinoline, [8,30,40] followed by transformation to their respective cyano, methoxy, phenyl, and amino derivatives. [7,14,17,39] The antiproliferative activity of 6,8dibromotetrahydroquinoline and 5,7-dibromo-8-hydroxyquinoline against several cancer cell lines was determined by the BrdU cell proliferation enzyme-linked immunosorbent assay (BCPE). [6][7][8] The results showed that 6,8-dibromotetrahydroquinoline and 5,7-dibromo-8-hydroxyquinoline significantly inhibited proliferation of HeLa, C6, and HT29 cells, as compared with 5-fluorouracil (5-FU) at 5 μg/ml and higher concentrations.…”

Decision making for promising quinoline‐based anticancer agents through combined methodology

“…[29] Cyano substituted 8-hydroxyquinolines were synthesized by metal-assisted substitution reaction according to our reported procedures. [3,22,26] Furthermore, the synthesis of 6,8-diphenylquinoline (12) via Suzuki coupling was also reported in our recent works. [26,30] The isolated compounds 2-5, 7, 11, and 12 were fully characterized by melting point, HRMS analysis, infrared, 1 H, 13 C, heteronuclear multiple bond correlation, and heteronuclear correlation nuclear magnetic resonance (NMR) spectroscopy in those papers.…”

“…In our previous publications, we showed that bromination is an easy functionalization method for quinolines starting from tetrahydroquinoline and the brominated tetrahydroquinolines and quinolines were transformed to their respective derivatives. [1,9,24,26] In our recent studies, brominated quinolines were synthesized according to reported procedures starting from 1,2,3,4-tetrahydroquinoline and 8-substituted quinoline. [8,9,[27][28][29] The brominated quinoline and tetrahydroquinolines were converted to a series of corresponding methoxy-, [1,9] cyano-, [9,24] silyl-, [9] thiomethyl-, [9] hydroxyl-, [29] and phenyl- [26] substituted derivatives of quinolines (∼60 analogs) by metal-assisted substitution reactions and Suzuki-Miyaura crosscoupling reactions.…”