“On Water” Palladium Catalyzed Direct Arylation of 1H-Indazole and 1H-7-Azaindazole

Abstract

The C3 direct arylation of 1H-indazole and 1H-7-azaindazole has been a significant challenge due to the lack of the reactivity at this position. In this paper, we describe a mild and an efficient synthesis of new series of C3-aryled 1H-indazoles and C3-aryled 1H-7-azaindazoles via a C3 direct arylation using water as solvent. On water, PPh3 was effective as a ligand along with a lower charge of the catalyst Pd(OAc)2 (5 mol%) at 100 °C, leading to C3-aryled 1H-indazoles or C3-aryled 1H-7-azaindazoles in moderate to good yields.

Sustainable Pd-Catalyzed Direct Arylation of Thienyl Derivatives with (Hetero)aromatic Bromides under Air in Deep Eutectic Solvents

“…For this reason, greener alternatives have been investigated and, in the last decade, DA reactions have been carried out in more environmentally friendly reaction media like cyclopentyl methyl ether, 51 dialkyl carbonates, 52,53 alcohols, 53 γ-valerolactone, 54 Rhodiasolv Polarclean, 55 ionic liquids, 56 and even water. 52,57 DESs have been employed as green solvents for DA reactions too, but, to the best of our knowledge, only two examples were reported in the literature so far. were used, the addition of small amounts of an organic solvent like cyclopentyl methyl ether was necessary to obtain good yields.…”

“…Unfortunately, DA reactions are usually run in aromatic solvents (Scheme ) like toluene or aprotic polar media like N , N -dimethylformamide (DMF) or N , N -dimethylacetamide (DMAc), which are, respectively, defined as “problematic” and “hazardous” by the CHEM21 solvent guide because of health, environmental, and safety issues. For this reason, greener alternatives have been investigated and, in the last decade, DA reactions have been carried out in more environmentally friendly reaction media like cyclopentyl methyl ether, dialkyl carbonates, , alcohols, γ-valerolactone, Rhodiasolv Polarclean, ionic liquids, and even water. , …”

Sustainable protocols for direct C–H bond arylation of (hetero)arenes

“…However, very recently El Kazzouli demonstrated that working "on water" with the less expensive Pd(OAc) 2 instead of PdCl 2 (dppf )•CH 2 Cl 2 and at 100 °C instead of 50 °C, direct C3 arylation of 1H-indazoles with (hetero)aryl iodides occurred in high yields. 173 The only report on the direct arylation of benzimidazoles in aqueous conditions was described in 2020 by Peddiahgari and co-workers: a family of Pd-PEPPSI complexes was tested in the direct C2 arylation of N-substituted benzimidazoles in a water/ ethanol 1 : 1 (v/v) mixture. 174 However, this work was actually mainly focused on the synthesis and catalytic performance of such complexes, rather than on the development of a highly sustainable direct C-H arylation protocol of benzimidazoles.…”

Strategies for the synthesis of water-soluble conjugated polymers

“…Mixtures of organic solvents and water are suitable for the polymerization of water-soluble monomers, but the use of water as the sole solvent would make this polymerization method greener and allow a better solubility of the polymer during the reaction, thus leading to an improvement in the molecular weights. Many research groups are investigating the utilization of aqueous media for direct arylation coupling reactions [51][52][53][54][55], and an increasing number of studies are now reporting water as the polymerization solvent. For instance, Ayalew and colleagues [31] reported, in 2018, a successful polymerization of water-soluble PEDOT made by DHAP using water as the only solvent.…”