A. Mahanta et al. / Tetrahedron Letters 56 (2015) 1780–1783
1781
potassium peroxymonosulfate17 and Amberlite IR 120 resin,18
acetonitrile, and THF and found good results in the case of 50%
aqueous methanol and aqueous acetonitrile (Table 1, entries 8
and 9) compared to aqueous acetonitrile. From this screening, we
observed the best results in the case of water as solvent (Table 1,
entry 10). A series of reactions were conducted to find the opti-
mized amount of the catalyst and oxidant. Firstly, when the reac-
tion was attempted with different amounts of the catalyst and
taking 2 mL of H2O2 it was found that 5 mg of the catalyst was ade-
quate for the efficient conversion of 1 mmol of phenylboronic acid
(Table 2, entries 4 vs 5). Next we tried to determine the optimized
amount of the oxidant by using 5 mg of catalyst and found that
0.2 mL of the oxidizing agent was sufficient to convert 1 mmol of
the phenylboronic acid to phenol24 (Table 2, entries 8 vs 9).
However, the reaction did not proceed in the absence of either bio-
silica or hydrogen peroxide.
20
H3BO3–H2O2,19 NaClO2 supported silver nano particle21 etc,.
Moreover, biologically, ipso hydroxylation plays a very important
role in the elimination of sulfonamide antibiotics.22
In the literature some reports are available where biosilica is
used as a support1 in many organic reactions. In continuation of
our efforts to develop an efficient protocol for the direct transfor-
mation of arylboronic acids to phenols, we herein, reported an effi-
cient, facile, and mild protocol for ipso-hydroxylation of
arylboronic acids to phenols with excellent yields which utilizes
biosilica as a catalyst and H2O2 (30% aqueous) as an oxidant, at
room temperature. Hydrogen peroxide is considered as a stoichio-
metric, environmentally acceptable oxidant that shows a high effi-
ciency per weight of oxidant.23
We started our ipso-hydroxylation protocol by studying the
effectiveness of H2O2 (30% aqueous) in the hydroxylation reaction
choosing phenylboronic acid as a model substrate and the reac-
tions were carried out at room temperature under aerobic condi-
tions (Scheme 1). At first we carried out the reaction by using
only H2O2 (2 mL) at room temperature and to our delight phenol
was detected as the sole product in 24 h. However, use of biosilica
as a catalyst for this reaction provided better yield (76%) of the pro-
duct (Table 1, entry 2). During the course of the reaction we
encountered solubility problem under solvent free conditions and
a sticky reaction mass was observed in the reaction vessel.
Therefore, to overcome this problem we have carried out the reac-
tion using 2 mL of water as solvent, excellent conversion to phenol
was observed under these conditions (Table 1, entry 3). We then
tried to fine tune the reaction conditions to obtain the optimized
reaction conditions for the conversion of phenylboronic acid to
phenol using aqueous H2O2 as oxidant and biosilica as the catalyst.
To study the effect of solvents in our system, we carried out the
reaction in the presence of various solvents by usingbiosilica as
the catalyst and results are summarized in Table 1 (entries 3–
10). The reaction was found to proceed in both protic and aprotic
solvents although significant variations in yields were noticed.
The best result was obtained when water was used as a solvent.
We also tried the same reaction in 50% aqueous methanol,
To evaluate the scope and limitations of the current procedure,
reactions of a wide array of electronically diverse arylboronic acids
were examined under optimized reaction conditions using biosi-
lica and hydrogen peroxide (Table 3).24 It has been observed that
the electronic nature and the position of the substituents had little
effect on the reaction process and both electron donating and with-
drawing substituted phenylboronic acids like Me, OMe, Et, F, Cl etc.
provided good to excellent yields. Moreover, sterically hindered as
well as hetero arylboronic acids also undergo easy transformation
with high yield (entries 10–13). Results are summarized in the
table 3.
A plausible mechanistic pathway for the ipso-hydroxylation of
arylboronic acid to phenol has been proposed (Fig. 1). It is assumed
that, initially biosilica reacts with H2O2 to form a silica-peroxide
composite [(i) in the figure] which then reacts with phenylboronic
acid to form an adduct (A) which upon rearrangement and subse-
quent water loss produced the adduct B, which upon hydrolysis
gave phenol.
The reusability of the catalyst is a great advantage in the cost
reduction of process chemistry. Therefore the reusability of the
biosilica catalyst was investigated. For that, we performed the
hydroxylation of phenylboronic acid using 1 mmol of the substrate
under the optimized reaction conditions. After the completion of
the first cycle, the catalyst was filtered and washed with diethyl
ether followed by water and then allowed to evaporate the water
in an oven overnight (100 °C) and was used for further reaction
of ipso-hydroxylation of phenylboronic acid. Surprisingly, the cata-
lyst remained efficient and the reaction afforded excellent yields
up to the sixth run (Table 4, entries 1–6).
H2O2 (30% aq.)
OH
B(OH)2
Catalyst
Scheme 1. ipso-Hydroxylation of phenylboronic acid with H2O2.
Table 1
Optimization of reaction conditiona for biosilica catalyzed ipso-hydroxylation of
Table 2
phenylboronic acid24
Optimization of amount of catalyst and oxidant for hydroxylation of phenylboronic
acida
H2O2 (30% aq.)
OH
B(OH)2
H2O2 (30% aq., 2 mL)
H2O (2 mL), rt
Solvent, Catalyst
B(OH)2
OH
Entry
Catalyst
Solvent (2 mL)
Time (min)
Yieldb (%)
Entry Amount of catalyst
(mg)
Amount of H2O2 (30% aq)
(mL)
Conversion
1
2
3
4
5
6
7
8
9
None
None
None
Water
Methanol
Acetonitrile
THF
DCM
Methanol/water (1:1)
Acetonitrile/water (1:1)
THF/water (1:1)
1440
45
0–5
0–5
15
25
15
10
15
57
76
93
90
87
70
89
90
90
80
Biosilica
Biosilica
Biosilica
Biosilica
Biosilica
Biosilica
Biosilica
Biosilica
Biosilica
1
2
3
4
5
6
7
8
9
50
30
10
5
3
5
5
5
5
2
2
2
2
2
1
0.5
0.2
0.1
Full
Full
Full
Full
Incomplete
Full
Full
Full
Incomplete
10
25
a
Reaction conditions: phenylboronic acid (1 mmol), H2O2 (30% aq, 2 mL), biosilica
(50 mg) unless otherwise noted.
a
Reaction condition: phenylboronic acid (1 mmol), water (2 mL), the progress of
the reaction was monitored by TLC.
b
Isolated yield.