An efficient and novel protocol was developed for a Cu-catalyzed Ullmann-type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride-based eutectic mixtures. Under optimized conditions, the reaction proceeded under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [CuI or CuII species] loading up to 5 mol% and K2CO3 as the base, providing the desired aryloxy derivatives in up to 98 % yield. The potential application of the methodology was demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e. g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin, and Chlorphenesin) on a 2 g scale in 70–96 % yield. Catalyst, base, and deep eutectic solvent could easily and successfully be recycled up to seven times with an E-factor as low as 5.76.
An efficient and novel protocol was developed for a Cu-catalyzed Ullmann-type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride-based eutectic mixtures. Under optimized conditions, the reaction proceeds under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [Cu(I) or Cu(II) species] loading up to 5 mol% and K 2 CO 3 as the base, providing the desired aryloxy derivatives in up to 98% yield. The potential application of the methodology is demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e.g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin and Chlorphenesin) on a 2-gram scale in 70–96% yield. The catalyst, the base, and the DES could easily and successfully be recycled up to seven times with an E-factor as low as 5.76
Ligand‐free Copper‐Catalyzed Ullmann‐type C–O Bond Formation in Non‐innocent Deep Eutectic Solvents under Aerobic Conditions
Quivelli, Andrea Francesca;Vitale, Paola;Perna, Filippo Maria;Capriati, Vito
2022-01-01
Abstract
An efficient and novel protocol was developed for a Cu-catalyzed Ullmann-type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride-based eutectic mixtures. Under optimized conditions, the reaction proceeded under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [CuI or CuII species] loading up to 5 mol% and K2CO3 as the base, providing the desired aryloxy derivatives in up to 98 % yield. The potential application of the methodology was demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e. g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin, and Chlorphenesin) on a 2 g scale in 70–96 % yield. Catalyst, base, and deep eutectic solvent could easily and successfully be recycled up to seven times with an E-factor as low as 5.76.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
