Efficient palladium‐catalyzed C‐S cross‐coupling reaction of benzo‐2,1,3‐thiadiazole at C‐5‐position: A potential class of AChE inhibitors

• Published in: Applied organometallic chemistry Vol. 34; no. 7
• Main Authors: Santos, Beatriz F., Pereira, Caroline F., Pinz, Mikaela P., Oliveira, Aline R., Brand, George, Katla, Ramesh, Wilhelm, Ethel A., Luchese, Cristiane, Domingues, Nelson L.C.
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.07.2020; Wiley Subscription Services, Inc
• Subjects: acetylcholinesterase inhibitors; Arylsulfanyl‐benzo‐2,1,3‐thiadiazole; Catalysis; Chemistry; Chemistry, Applied; Chemistry, Inorganic & Nuclear; Cross coupling; C‐S bond; Derivatives; Inhibitors; Palladium; Physical Sciences; Reaction time; Science & Technology; Thiadiazoles; Thiols; C-S bond; acetylcholinesterase inhibitors; 1; SUBSTITUTION; Arylsulfanyl-benzo-2; SOLAR-CELLS; ARYLATION; cross-coupling; DERIVATIVES SYNTHESIS; ARYL; 3-thiadiazole; SOLVENT
• ISSN: 0268-2605; 1099-0739
• DOI: 10.1002/aoc.5650

Functionalization of 2,1,3‐benzothiadiazole (BTD) with thiols at C‐5 position remains low explored. Moreover, the arylthiol‐substitutions at this position are also unexplored and can not be found by a SN2 or SN1 reaction. In this sense, herein we present a new palladium‐catalyzed methodology for a wide variety of unpublished 5‐arylsulfanyl‐benzo‐2,1,3‐thiadiazole derivatives synthesis with moderate to high yields using a low catalytic loading of Pd(L‐Pro)2 as low‐coast, and efficient catalyst in low reaction time. Besides, we concluded that the pKa of thiol species has an important role in this catalysis, mainly in the CMD like catalytic cyclo process, which strongly interferes in the reaction yields. Furthermore, arylsulfanyl‐benzo‐2,1,3‐thiadiazoles derivatives have been assessed (in vitro) as potential acetylcholinesterase inhibitors. Palladium‐catalyzed C‐S cross‐coupling reaction for access to arylsulfanyl‐benzo‐2,1,3‐thiadiazole derivatives. A series of unpublished sulfur compounds were obtained using a low catalytic loading of palladium prolinate in short reaction time. Besides, the arylsulfanyl‐benzo‐2,1,3‐thiadiazole derivatives were tested in vitro as acetylcholinesterase inhibitors and all compounds exhibited anticholinesterase activity.