Efficient Cleavage of Alkyl Aryl Ethers Using an Ionic Liquid
Bull. Korean Chem. Soc. 2013, Vol. 34, No. 1 177
tion. The dealkylation reaction time can vary from several
minutes to 40 minutes depending on the protecting groups
and the substituents of the protected phenolic substrates.
Table 3 summarized the deethylation and depropylation
reactions of the substrates of various functional group sub-
stituents. Deethylation generally showed a slightly better
reactivity and selectivity than depropylation. Clean conver-
sions to the corresponding phenols with no noticeable side-
products were observed for the deethylation reactions. Regard-
less of electronic effect of substituents such as electron
releasing and electron withdrawing, most substrates required
the similar microwave power and irradiation time. We pre-
sumed that substrates with electron withdrawing substituents
might need a shorter reaction time or a weaker irradiation
power as the reaction would proceed in an SN2 manner, but
such substituent influence was observed only in the case of
nitro substituted ethoxy phenol in a little extent (Table 3,
entry 8); 1-ethoxy-3-nitrobenzene needed slightly shorter
reaction time as 25 min while others needed 30-40 min. This
suggests that comparable and high activation energies are
necessary for the nucleophilic substitutions. Both 1-ethoxy-
naphthalene and 2-propoxynaphthalene were converted into
the corresponding naphthols in excellent yields (Table 3,
entries 1 and 9). As the deethylation is very effective under
the reaction conditions, deethylation of all the acetylated
ethoxybenzenes occurred equally well irrespective of the
substituent positions at ortho, meta, and para (Table 3,
entries 2-4). Halogen groups were fairly compatible with the
reaction conditions; most of chloro- and bromo- substituents
remained intact during the deethylation (Table 3, entries 5, 6,
and 1413). In some n-propyl protected phenolic substrates
such as entries 12 and 13, full conversions were achieved
after a longer reaction time, but tar materials were observed,
lowering the product isolation yields. In these cases, the best
yields were obtained upon ca. 90% conversion. The other
substituents such as phenyl, isopropyl and cyano group were
also compatible under the reaction conditions, showing clean
conversion to the corresponding phenols.
As we noticed in the test reaction of 4-benzyloxy(bi-
phenyl), debenzylation was much more efficient than other
dealkylations. When the same reaction protocol, that is,
three equivalent of [bmim][Br] under 20 W microwave
irradiation, was applied, much shorter time was required for
the completion, implying that the better reactivity of benzyl
group towards nucleophilic substitution reactions (Table 4).
A time range of 2.5-10 minutes was enough for the comple-
tion of debenzylayion, whereas 20-40 minutes was needed
for demethylation, deethylation and depropyalation. Similar-
ly to dealkyation, electronic effect was not very critical. All
the substrates with electron releasing or electron withdraw-
ing substituents were converted into the corresponding
phenols with excellent yields.
In conclusion, we successfully broadened the scope of the
microwave-assisted dealkylation protocol with ionic liquid
[bmim][Br] to the dealkylation of ethyl-, n-propyl-, and
benzyl protected phenolic compounds. The presented pro-
tocol employs ionic liquid [bmim][Br] as a sole reagent. It
does not need any other additional agents such as strong
acids to activate the ether bond towards nucleophilic cleav-
age. The ionic liquid, [bmim][Br], is effective enough not
only to cleave the protecting group but also to dissolve most
of the substrates, and thus, additional solvents are not
necessary. Low power microwave irradiation with consistent
air cooling in a short time was proved to be very effective for
the cleavage process, improving the reaction conversions
and yields. The conventional heating using hot oil bath
shows low conversions even for a prolonged time and the
prolonged reaction time often causes the decomposition of
the materials. Such disadvantage of the conventional heating
method can be superbly overcome by incorporating the
microwave irradiation technique. By demonstrating that this
highly efficient protocol can be utilized in cleaving various
kinds of alkyl aryl ethers including ethyl, n-propyl, benzyl
groups, we are able to provide researchers in this area with
more choices in the selection of protection groups.
Table 4. Debenzylation reactions of various benzyl aryl ethers
using [bmim][Br] under microwave irradiationa
Entry
1
Product (ArOH)
Time (min)
2.5
Yield (%)b
99
2
3
5
99
99
Experimental Section
10
Representative Procedure. To a microwave tube was
added alkyl aryl ether (1.0 mmol) and 1-n-butyl-3-methyl
imidazolium bromide (0.65 g, 3.0 mmol). The reaction tube
was flushed with argon and then was irradiated at 20 W for
the designated time period with air-flow cooling to prevent
overheating (power control mode). After cooled to room
temperature, the reaction mixture was acidified with 1 N
HCl solution and extracted with ethyl acetate (3 × 15 mL).
The combined organic layer was washed with water and
brine, and dried over anhydrous MgSO4 and the solvent was
evaporated under vacuum. Purification of the crude product
4
5
5
96
97
10
6
5
98
aAll reactions were carried out on a 1 mmol scale of benzyl aryl ether
using 3.0 equiv of [bmim][Br]. bIsolated yields of > 95% purity as
determined by GC and 1H-NMR.