The Hydrolysis of p-Substituted Styrene Oxides 73
nism, to deal with a specific acid catalysis process is of great help because generally they all follow the same pattern: a rapid protonation of the substrate as a preequilibrium, followed by a slow step not involving proton transfer (Scheme 11.4).
r
In this case, the protonation of the oxygen in 1 would lead to 5 that after breaking
the C-O bond in the slow step, would be transformed into carbocation 6. Attack of
water in 6 followed by deprotonation of the intermediate alcohol 7 would form the
final diols 2.
O
H
O
H
H
CH 2 OH
H
X = MeO, Me, H, Cl, NO 2
H +
HCCH 2 OH
18 OH
X
X
X
slow
H 2
18 O
H 2
18 O
X
1
5
6
2
HCCH 2 OH
18 OH 2
X
-H +
7
Scheme 11.4
We have to check now if the formulation of a mechanism involving a carbocation intermediate is supported by the rest of the experimental data. The isotopic
t
labeling experiments carried out with H 2
18
O confirm that the attack of the nucleophile occurs exclusively at the benzylic position, which is in agreement with the
mechanism proposed in Scheme 11.4 (labeled atoms in red). Furthermore, the
formation of a planar intermediate, like a carbocation, should justify the fact that
when chiral (+)-styrene oxide is employed, only the racemic diol is obtained.
Why then does the acid methanolysis of (+)-styrene oxide lead to the diol with
89% inversion of configuration at the benzylic position? Clearly the high percentage inversion of the configuration is incompatible with the formation of a planar
intermediate like a carbocation. However, we have made a change in the solvent
and methanol is more nucleophilic than water. The inversion of the configuration
could be due to a S N 2-type attack by the nucleophile at the benzylic position before the carbocation is formed. In consequence, a competition between S N 2 displacement by solvent molecules (inversion) and ionization (racemization) may
happen. By considering this possibility, in Scheme 11.5 we have indicated the
possible mechanisms for the acid solvolysis of substituted styrene oxides. After
the protonation of the oxirane ring two alternative pathways could be considered.
Electron-donating groups in para position of the aromatic ring and non-nucleophilic solvents will allow for the evolution of protonated oxiranes 5 to carbocations 6 (path a), whereas highly nucleophilic solvents and absence of p-electrondonating groups would favor the direct solvolysis of the oxirane ring (path b).
nism, to deal with a specific acid catalysis process is of great help because generally they all follow the same pattern: a rapid protonation of the substrate as a preequilibrium, followed by a slow step not involving proton transfer (Scheme 11.4).
r
In this case, the protonation of the oxygen in 1 would lead to 5 that after breaking
the C-O bond in the slow step, would be transformed into carbocation 6. Attack of
water in 6 followed by deprotonation of the intermediate alcohol 7 would form the
final diols 2.
O
H
O
H
H
CH 2 OH
H
X = MeO, Me, H, Cl, NO 2
H +
HCCH 2 OH
18 OH
X
X
X
slow
H 2
18 O
H 2
18 O
X
1
5
6
2
HCCH 2 OH
18 OH 2
X
-H +
7
Scheme 11.4
We have to check now if the formulation of a mechanism involving a carbocation intermediate is supported by the rest of the experimental data. The isotopic
t
labeling experiments carried out with H 2
18
O confirm that the attack of the nucleophile occurs exclusively at the benzylic position, which is in agreement with the
mechanism proposed in Scheme 11.4 (labeled atoms in red). Furthermore, the
formation of a planar intermediate, like a carbocation, should justify the fact that
when chiral (+)-styrene oxide is employed, only the racemic diol is obtained.
Why then does the acid methanolysis of (+)-styrene oxide lead to the diol with
89% inversion of configuration at the benzylic position? Clearly the high percentage inversion of the configuration is incompatible with the formation of a planar
intermediate like a carbocation. However, we have made a change in the solvent
and methanol is more nucleophilic than water. The inversion of the configuration
could be due to a S N 2-type attack by the nucleophile at the benzylic position before the carbocation is formed. In consequence, a competition between S N 2 displacement by solvent molecules (inversion) and ionization (racemization) may
happen. By considering this possibility, in Scheme 11.5 we have indicated the
possible mechanisms for the acid solvolysis of substituted styrene oxides. After
the protonation of the oxirane ring two alternative pathways could be considered.
Electron-donating groups in para position of the aromatic ring and non-nucleophilic solvents will allow for the evolution of protonated oxiranes 5 to carbocations 6 (path a), whereas highly nucleophilic solvents and absence of p-electrondonating groups would favor the direct solvolysis of the oxirane ring (path b).