Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues.
1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2'-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line.
Chimie et Photonique Moléculaires, Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1, Bâtiment 10A, Case 1003, Campus de Beaulieu, 35042 Rennes, France.
Elisabeth
E
Nagaradja
Chimie et Photonique Moléculaires, Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1, Bâtiment 10A, Case 1003, Campus de Beaulieu, 35042 Rennes, France; Laboratoire de Synthèse Organique Appliquée, Faculté des Sciences, Université d'Oran 1 Ahmed Ben Bella, BP 1524 El M'Naouer, 31000 Oran, Algeria.
Ghenia
G
Bentabed-Ababsa
Chimie et Photonique Moléculaires, Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1, Bâtiment 10A, Case 1003, Campus de Beaulieu, 35042 Rennes, France.
Mathieu
M
Scalabrini
Chimie et Photonique Moléculaires, Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1, Bâtiment 10A, Case 1003, Campus de Beaulieu, 35042 Rennes, France. Electronic address: floris.chevallier@univ-rennes1.fr.
Floris
F
Chevallier
UMR 7565, Laboratoire de Structure et Réactivité des Systèmes Moléculaires Complexes, CNRS-Université de Lorraine, Faculté de Pharmacie, 5 rue Albert Lebrun, BP 80403, 54001 Nancy, France.
Stéphanie
S
Philippot
UMR 7565, Laboratoire de Structure et Réactivité des Systèmes Moléculaires Complexes, CNRS-Université de Lorraine, Faculté de Pharmacie, 5 rue Albert Lebrun, BP 80403, 54001 Nancy, France.
Stéphane
S
Fontanay
UMR 7565, Laboratoire de Structure et Réactivité des Systèmes Moléculaires Complexes, CNRS-Université de Lorraine, Faculté de Pharmacie, 5 rue Albert Lebrun, BP 80403, 54001 Nancy, France. Electronic address: raphael.duval@univ-lorraine.fr.
Raphaël E
RE
Duval
UNESCO Chair of Belarusian State University, 14 Leningradskaya Str., Minsk 220030, Belarus. Electronic address: hys@tut.by.
Yury S
YS
Halauko
UNESCO Chair of Belarusian State University, 14 Leningradskaya Str., Minsk 220030, Belarus.
Oleg A
OA
Ivashkevich
Research Institute for Physico-Chemical Problems of Belarusian State University, 14 Leningradskaya Str., Minsk 220030, Belarus.
Vadim E
VE
Matulis
Centre de Diffractométrie X, Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1, Bâtiment 10B, Campus de Beaulieu, 35042 Rennes, France.
Thierry
T
Roisnel
Chimie et Photonique Moléculaires, Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1, Bâtiment 10A, Case 1003, Campus de Beaulieu, 35042 Rennes, France. Electronic address: florence.mongin@univ-rennes1.fr.
Florence
F
Mongin
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014230:Triazoles / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D013267:Stilbenes; D014230:Triazoles; D000077185:Resveratrol
Antiproliferative activity; CH-acidity; Deprotonative metalation; Resveratrol analogue; Triazole