The palladium(II) aqua complex cis-[Pd(en)(H2O)(2)](2+) catalyzes the
alcoholysis of urea into alkyl carbamate and ammonia. The observed rat
e constants for the ester formation fall in the range from 1.8 x 10(-5
) to 5.9 x 10(-1) min(-1) at 313 K and pH 3.3, depending on the alcoho
l. This catalyzed reaction is at least 10(5) times faster than the unc
atalyzed alcoholysis of urea under the same conditions. This is the fi
rst example of catalytic, nonhydrolytic cleavage of the amide bond in
urea. The following steps in the mechanism of the methanolysis reactio
n are studied quantitatively: binding of urea to the catalyst in the p
resence of various alcohols or various concentrations of water, direct
methanolysis of O-bound and N-bound urea, formation of carbamic acid
(NH2COOH) coordinated to palladium(II) via the nitrogen atom, methanol
ysis of this intermediate, and the fast dissociation resulting in free
methyl carbamate. Ammonia, a product of alcoholysis, inhibits this re
action by binding to palladium(II). When, however, ammonia is sequeste
red by the silver(I) cation, alcoholysis becomes relatively fast, and
catalytic turnover is achieved. Various alcohols are compared in their
reactivity toward urea. The effects of nucleophilicity, steric bulk,
size, and additional hydroxyl groups (in diols) are examined. The intr
amolecular alcoholysis in the 2,6-dithia-1, 8-octanediol complex cis-[
Pd(C6H14O2S2)(H2O)(2)](2+) results in at least 100-fold rate enhanceme
nt relative to the intermolecular alcoholysis by cis-[Pd(en)(H2O)(2)](
2+). Alkyl carbamates do not hydrolyze further into carbamic acid and
alcohol. Aryl carbamates do hydrolyze further, and this reaction requi
res the palladium(ZI) aqua complex as a catalyst. Carbamic acid then s
pontaneously decomposes into carbon dioxide and ammonia. Observed rate
constants for the appearance and disappearance of aryl carbamates agr
ee with the relative nucleophilicities of aryl alcohols. This study of
the catalysis by a metal complex may contribute to the understanding
of the metalloenzyme urease. We propose a new method, alcoholysis, for
cleaving amide bonds in peptides and proteins.