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

Abstract

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 In this sense, herein we present a new palladium‐catalyzed methodology for a wide variety of unpublished 5‐arylsulfanyl‐benzo‐2,1,3‐thiadiazole derivatives synthesis with moderate to high yields using a low catalytic loading of Pd(L‐Pro)2 as low‐coast, and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.

Pd/RHA and Pd/BPA as Eco-Friendly Heterogeneous Catalysts: Microwave-Assisted C–S Cross-Coupling Reaction in DMF

“…Importantly, we compared our results to those of previously reported protocols. [14][15][16] Many reports have some drawbacks, such as high temperatures, excess catalyst loading, inert environments, and long reaction times. However, our method has various advantages, such as an eco-friendly catalyst, reusability up to five cycles, very minimal catalyst loading, low cost, low temperature, and microwave-assisted conditions, all of which can be employed in the pharmaceutical industry.…”

“…A plausible mechanism was proposed as shown in Scheme 5. [15] When sulfur species react with catalyst through a CMD-like transition state, generating an intermediate B. In the next step, an intermediate C is produced by the loss of disulfide as a byproduct.…”

“…The sample mass dilution was performed with KBr. ( 22) General Procedure for the Synthesis of 5-Phenylthio-2,1,3benzothiadiazoles 15 Benzene thiols (0.45 mmol), 5-bromo-2,1,3-benzothiadiazole…”

“…Recently, Domingues and coworkers reported a one-pot synthesis of 5-arylsulfanyl-benzo-2,1,3-thiadiazole derivatives in DMF at 110 °C for 6 h utilizing palladium(II) proline as a heterogeneous catalyst. [15] Kamboj et al reported the synthesis of 4,7-disulfanyl-benzo-2,1,3-thiadiazoles in the presence of palladium catalyst, which further oxidized into 4,7-disulfonyl-benzo-2,1,3-thiadiazoles. [16] Alves and coworkers demonstrated copper nanoparticles mediated onepot synthesis of arylsulfanyl-benzo-2,1,3-thiadiazoles using 4,7-dibromo-benzo-2,1,3-thiadiazole with 4-methoxybenzene thiol in DMSO and KOH as a base under nitrogen atmosphere for 24 h. [17] The above-mentioned reports contain reactions at position 5 and 4.…”

Anchored Pd(0) Nanoparticles on Synthetic Talc for the Synthesis of Biaryls and a Precursor of Angiotensin II Inhibitors

“…With this goal, our group has been investigating crosscoupling reactions, and we have previously described protocols for C-S cross-coupling by using a heterogeneous palladium catalyst. 16,17 As a continuation of this research, we herein introduce synthetic talc as an efficient, inexpensive, and eco-friendly heterogeneous support for immobilized palladium catalyst synthesis -LACOB-Pd1 and LACOB-Pd4. The difference between these two catalysts lies in the labels 1 and 4 which refer to the initial loading of the palladium salt added to synthetic talc (see the Supporting Information).…”