Rocío García-Álvarez

Metal-catalyzed amide bond forming reactions in an environmentally friendly aqueous medium: nitrile hydrations and beyond

Amides are versatile building blocks in synthetic organic chemistry, presenting a wide range of pharmacological applications, and are used as raw materials in industry for the large-scale production of engineering plastics, detergents and lubricants. The development of green procedures for the synthesis of this relevant class of compounds from various starting materials, which replace antiquated methods using carboxylic acid derivatives and amines, is therefore of prime interest in modern chemistry. In this review article, a survey of metal-catalyzed synthetic approaches of amides conducted in an environmentally friendly aqueous medium is given.

Thiazolyl-phosphine hydrochloride salts: effective auxiliary ligands for ruthenium-catalyzed nitrile hydration reactions and related amide bond forming processes in water

A series of water-soluble N-protonated thiazolyl-phosphine hydrochloride salts have been synthesized and coordinated to the ruthenium(II) fragment [RuCl2(η6-p-cymene)]. The resulting complexes were evaluated as potential catalysts for the selective hydration of nitriles to primary amides in environmentally friendly aqueous medium. The best results in terms of activity were achieved when tris(5-(2-aminothiazolyl))phosphine trihydrochloride was used as ligand. Using the Ru(II) complex 9 derived from this salt (3 mol%), the catalytic reactions proceeded cleanly in pure water at 100 °C without the assistance of any additive, affording the desired amides in high yields (>78%) after short reaction periods (0.5–7 h). The process was operative with both aromatic, heteroaromatic, α,β-unsaturated and aliphatic nitriles, and tolerated several functional groups. The utility of 9 in promoting the formation of primary amides in water by catalytic rearrangement of aldoximes and direct coupling of aldehydes with NH2OH·HCl has also been demonstrated.

Ruthenium-catalyzed one-pot synthesis of primary amides from aldehydes in water

The readily available arene–ruthenium(II) complex [RuCl2(η6-C6Me6){P(NMe2)3}] (5 mol%) proved to be an efficient catalyst for the direct synthesis of primary amides from aldehydes and hydroxylamine hydrochloride (NH2OH·HCl) in water at 100 °C. The process, which requires the presence of NaHCO3 to catch the HCl released during the formation of the key aldoxime intermediates, was operative with both aromatic, heteroaromatic, α,β-unsaturated and aliphatic aldehydes, and tolerated several functional groups. A greener approach using commercially available NH2OH solution (50 wt.% in water) is also presented.