Aldehyde- and
ketone-derived cyanohydrins were reacted with the
nitrile hydration catalysts [PtCl(PR(2)
OH){(PR(2)O)(2)H}] (1) and Cp(2)Mo(
OH)(
OH(2))(+) (2) under a variety of hydration reaction conditions. In general, the cyanohydrins were hydrated to the
amides rather slowly using these catalysts, but no subsequent hydrolysis of the
amide products occurred. Catalyst 2 was much less reactive than catalyst 1, showing at best trace amounts of
amide product. Product inhibition-, substrate inhibition-, and
cyanide poisoning-tests demonstrated that coordination of
cyanide, generated by dehydrocyanation of the cyanohydrins, is responsible for the generally low catalytic activity of 1 and 2 with
cyanohydrin substrates. Addition of KCN to reaction mixtures of
acetonitrile and 1 gave a linear plot of rate versus
cyanide concentration, indicating that binding of
cyanide to the catalysts is irreversible. Density functional theory (DFT) calculations showed that, for the hydration reaction catalyzed by 2, the formation of most intermediates and the overall reaction itself are energetically more favorable for
lactonitrile (a
cyanohydrin) than for 3-hydroxypropionitrile (not a
cyanohydrin). From this result, it is concluded that, from an electronic standpoint, there is no intrinsic reason for the lack of reactivity observed for cyanohydrins, a result consistent with the finding that the slow hydration reactivity is caused by
cyanide poisoning. In addition, DFT calculations showed that, for
nitriles in general (not necessarily cyanohydrins), product inhibition occurs because coordination of the
amide product to the
metal center is stabilized by isomerization to the more strongly bonded iminol tautomer.