Page 659 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

16
The mechanism of this hydrolysis reaction has been studied in great detail. The 641
mechanism is the reverse of that for acetal formation. Acetal protonation is followed
SECTION 7.2
by elimination of an alcohol molecule. The resulting intermediate is a stabilized
carbocation. Addition of water and a second acid-catalyzed elimination lead to the Hydration and Addition
of Alcohols to Aldehydes
product. and Ketones
+
HOR'
+
R C(OR') 2 + H + R C R C OR' + R'OH
2
2
2
OR'
+ OR' OR'
R C OR' + H O R C R C + H +
2
2
2
2
+ OH 2 OH
OR' +
R C + H + R C OH + R'OH
2
2
OH
+
R C OH R C = O + H +
2
2
Some of the evidence that has helped to establish the general mechanism is as follows:
1. Isotopic-labeling experiments have established that C−O bond rupture occurs
between the carbonyl carbon and oxygen; substitution at the alcohol C−O
bond is not involved.
2. For most acetals, the reaction is specific acid catalyzed, which is consistent with
the existence of a preequilibrium in which the acetal is protonated. The proton
assists the departure of the alkoxy group by converting it to a better leaving
group. In essence, this cleavage step is an S 1 reaction with the remaining
N
alkoxy group stabilizing the carbocation formed by ionization.
3. Hammett treatments show good correlations with large negative values for the
hydrolysis of acetals of aromatic aldehydes, which is consistent with the devel-
opment of a positive charge at the carbonyl center in the rate-determining step.
4. Solvent isotope effects are usually in the range k D 2 O /k H 2 O = 2–3. These values
reflect the greater equilibrium acidity of deuterated acids (see Section 3.7.1.1)
and indicate that the initial protonation is a fast preequilibrium.
Acetal hydrolyses usually exhibit specific acid catalysis, in agreement with a
mechanism involving rate-determining cleavage of the conjugate acid of the reactant.
However, general acid catalysis is observed in certain acetals and ketals in which
17
special structural features reduce the energy required for C−O bond cleavage. Thus,
hydrolysis of each of the acetals shown in Scheme 7.1 exhibits general acid catalysis,
and each acetal has a structural feature that facilitates C−O bond heterolysis. Reducing
the energy requirement for C−O bond cleavage permits the proton transfer step
to become partially rate determining and results in the observation of general acid
catalysis.

16 E. H. Cordes and H. G. Bull, Chem. Rev., 74, 581 (1974).
17
T. H. Fife, Acc. Chem. Res., 5, 264 (1972).