4.3 Hydration of Nitriles
As amides are important structural motifs both in pharmaceuticals and bulk
chemicals, their synthesis via hydration of nitriles has attracted considerable attention from the organic synthesis community. Several groups have used metal pincer
complexes to catalyse this reaction (Scheme 48).
In 2015, the Piers group reported the use of pincer complex 48 as catalyst for the
hydration of nitriles to the analogous amides [90]. With low catalyst loadings
(0.05–0.5 mol%) and without additives, excellent yields were achieved at 80
C
using (hetero)aromatic and aliphatic nitriles as substrates. Substrates containing
acidic groups such as phenols or acetone cyanohydrin did not react. Acrylonitrile
did react, but the oxa-Michael addition with isopropanol (used as a solvent) was a
major side reaction. The crystal structure of complex 48 showed an unusually long
Scheme 47 Aza-Michael addition of amines to nitriles catalysed by 47
Scheme 48 Hydration of nitriles catalysed by pincer complexes
Catalytic Conversion of Nitriles by Metal Pincer Complexes
365