Silica chloride: An efficient promoter for oxidation of arylboronic acids to phenols

Article abstract of DOI:10.1016/j.tetlet.2017.07.041

This work reports simple, highly efficient protocol for the oxidation of arylboronic acids. Various arylboronic acids were selectively and completely converted into their corresponding oxidized phenols using H₂O₂ as an oxidant in presence of catalytic amount of silica chloride. The results show that silica chloride is a suitable and efficient promoter for the oxidation of arylboronic acids. Heterogeneous catalyst, mild reaction conditions, easy availability of the reagent, easy work-up, excellent yield of corresponding phenols, short reaction time and broad substrate scope makes this protocol attractive and a practical alternative to the existing methods.

Full text of DOI:10.1016/j.tetlet.2017.07.041

Accepted Manuscript
Silica chloride: An efficient promoter for oxidation of arylboronic acids to phe-
nols
Ravindra B. Wagh, Jayashree M. Nagarkar
PII:
S0040-4039(17)30887-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.07.041
TETL 49123
Reference:
Tetrahedron Letters
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Accepted Date:
9 June 2017
7 July 2017
10 July 2017
Please cite this article as: Wagh, R.B., Nagarkar, J.M., Silica chloride: An efficient promoter for oxidation of
arylboronic acids to phenols, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.07.041
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Ravindra B. Wagh and Jayashree M. Nagarkar*

1
Tetrahedron Letters
Silica chloride: An efficient promoter for oxidation of arylboronic acids to phenols
Ravindra B. Wagh and Jayashree M. Nagarkar*
a Department of Chemistry, Institute of Chemical Technology, Matunga, Mumbai – 400019, India.
E-mail: jm.nagarkar@ictmumbai.edu.in Tel.: +91 22 33611111/2222
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
This work reports simple, highly efficient protocol for the oxidation of arylboronic acids.
Various arylboronic acids were selectively and completely converted into their corresponding
oxidized phenols using H2O2 as an oxidant in presence of catalytic amount of silica chloride.
The results show that silica chloride is a suitable and efficient promoter for the oxidation of
arylboronic acids. Heterogeneous catalyst, mild reaction conditions, easy availability of the
reagent, easy work-up, excellent yield of corresponding phenols, short reaction time and broad
substrate scope makes this protocol attractive and a practical alternative to the existing methods.
Available online
Keywords:
Oxidation
Arylboronic acid
Phenol
2017 Elsevier Ltd. All rights reserved.
Silica chloride
H2O2
1. Introduction
experimental procedures simple. Silica chloride (SC) is one of
the most versatile and utilized heterogeneous solid acid catalysts.
Phenols are the most important starting materials for synthesis
of various industrial products, such as pharmaceuticals, agro-
chemicals, polymers etc.1-3 Phenols represent an important class
of compounds due to their properties, reactivity and mostly of
industrial importance.4 Therefore, the synthesis of phenols attract
the attention of chemist. Phenols are typically synthesized from
aryl halides via nucleophilic substitution with metal hydroxides
under harsh reaction conditions.5 Oxidation of arylboronic acid to
phenol is the most straightforward reaction. This oxidation
process is also termed as “ipso-hydroxylation” of arylboronic
acid. Arylboronic acids are inexpensive, stable, safe to use and
key reagent found in synthetic chemistry.6-7 In recent years,
chemical research is directed towards developing green
processes. High atom economy is also an essential parameter for
overall process efficiency. Previous reports suggested that
It is also cost effective, insoluble in organic solvents and used in
various organic transformations.22-26 Generally, silica chloride is
prepared by reaction of silica gel with thionyl chloride.27(a) In this
context, with the aim to improve efficiency and eco-friendly
conditions of catalytic processes. We have developed a new
catalytic oxidation system, Silica chloride-H2O2 as a continuation
of our research work on oxidation of organic compounds.28-29
Herein, we report selective oxidation of arylboronic acid to
phenol compounds in presence of catalytic amount of silica
chloride and H2O2 as oxidant with acetonitrile (MeCN) as solvent
at room temperature (Scheme 1).
Scheme 1 Oxidation of arylboronic acids to phenols
oxidation of arylboronic acid is carried out with metals such as
11
Cu and Ru8-9, N-Oxide10, NaClO2
,
NH2-OH12, Oxone13,
The present protocol is found to be effective with MeCN as a
solvent. Surprisingly, simple addition of phenylboronic acid in
MeCN in the presence of silica chloride as a catalyst using H2O2
at room temperature resulted in a dramatic exothermic reaction.
This led to complete conversion of phenylboronic acid to phenol
within few minutes. This system offers high selectivity, purity,
excellent yields, metal free approach and easy workup process.
MCPBA14 etc. This type of oxidation is also carried out with
H2O2 and several reports are available on it.15-20 Oxidation also
worked well with photocatalyst ɑ-Fe2O3.21 However, by
acknowledging all reported work in this field, hazardous metal
contamination or preparation and use of metal catalysts or
expensive catalyst, solvents, oxidants, long reaction time, high
temperature, toxic waste generation, tedious workup etc.
significantly lower their appeal. Therefore, development of new
oxidation system to overcome these drawbacks is very much
required.
Initially various oxidants were tried for the oxidation of
phenylboronic acid 1a (PBA) to phenol 2a in the presence of SC
as a catalyst and MeCN as a solvent. Table 1 (entries 1-6)
indicates that 30% H2O2 is the best oxidant which gave 100%
conversion and selectivity with short reaction time. Other
oxidants were found to give poor conversion even after carrying
the reaction at room temperature for 30 minutes. In addition to its
catalytic oxidation performance, H2O2 is superior to other
oxidants in terms of its environmentally benign property.
Hydrogen peroxide known as a green oxidant is cheap,
attractive, readily available and eco-friendly with water as a
byproduct. As per principles of green chemistry, the process is
said to be ‘green’ if techniques/chemicals used are eco-friendly.
Heterogeneous reagents have gained significant attraction due to
economic and environmental considerations. They can be
handled and removed from reaction mixture very easily, making

2
Tetrahedron Letters
Table 1 Comparative study with various oxidants
obtained only with SC while other catalysts failed to give such
high conversion of 1a to 2a (Table 3, entries 1-5). Silica bromide
also gave 90% conversion but the procedure for preparation of
silica bromide is difficult. This proves that SC is the most
suitable catalyst for the oxidation of 1a to 2a. During catalyst
screening study, SC showed excellent catalytic activity and
efficiency for the oxidation of 1a to 2a. We investigated the
influence of various amounts of SC (Table 3, entries 6-8) on the
reaction. When molar ratio was 0.2 - 0.4 mmol, the reaction did
not go to completion even after 30 min. (Table 3, entries 6-7).
We found that higher conversion and selectivity was obtained
with SC at 0.5 mmol (Table 3, entry 2). Similar result was
obtained by increasing molar ratio of SC from 0.5 – 0.6 mmol
(Table 3, entry 8). This shows that 0.5 mmol of SC is sufficient
for complete conversion of 1a to 2a.
Entry
Oxidant
(equiv.)
Time
(min)
Conv.b
(%)
Selectivityb
(%)
2a
100
64
1
2
3
4
5
6
30% H2O2
Oxone
05
30
30
30
30
30
100
64
71
81
49
55
m-CPBA
70% TBHP
UHP
71
81
49
K2S2O8
55
aReaction conditions: 1a (1 mmol), MeCN (3.0 mL), silica chloride (0.5
mmol), oxidant (1.0 equiv.), temp. (30-35 C), bconversion and selectivity
determined by GC with the area normalization method.
Oxidant plays a key role in this reaction. The effect of amount
of the oxidant on the reaction was studied by varying the amount
of H2O2 from 0.5-1.1 equiv. (Table 2, entries 1-5). H2O2 turned
out to be the best oxidant as it gave 100% conversion of starting
material (Table 2, entries 4-5). It was observed that 1.0 equiv. of
H2O2 gave 100% conversion and selectivity of 1a to 2a (Table 2,
entry 4). Low conversion was observed when H2O2 was added in
less molar ratios (Table 2, entries 1-3). When we increased the
amount of H2O2 from 1.0 to 1.1 equiv., we obtained similar result
as of 1.0 equiv. of H2O2 (Table 2, entry 5). The reaction did not
go to completion in the absence of H2O2 and/or SC (Table 2,
entries 6-8). The product conversion was very less under solvent
free reaction condition (Table 2, entry 9). Even though the
reaction in MeCN as a solvent goes to the completion, out of
scientific curiosity, we carried out model reaction in different
solvents such as ethanol (EtOH), water (H2O), chloroform
(CHCl3), toluene, ethyl acetate (EtOAc), tetrahydrofuran (THF),
dichloromethane (DCM), dimethylformamide (DMF), dimethyl
sulfoxide (DMSO) and acetone (Table 2, entries 10-19). This
indicates that the said reaction is sensitive to solvents.
Table 3 Comparative study with various catalysts and catalyst
loading (silica chloride)
Entry
Catalyst
Catalyst
(mmol)
Time
(min)
Conv.b
(%)
Selectivityb
(%)
2a
1
2
3
4
5
6
7
8
Silica gel
Silica chloride
Silica bromide
Silica sulfuric acid
Dowex-50
0.5
0.5
0.5
0.5
0.5
0.2
0.4
0.6
60
05
05
60
60
30
30
05
21
100
90
21
100
90
70
70
19
19
Silica chloride
Silica chloride
Silica chloride
45
45
78
78
100
100
aReaction conditions: 1a (1 mmol), MeCN (3.0 mL), catalyst (mmol), 30%
H2O2 (1.0 equiv.), temp. (30-35 C), bconversion and selectivity determined
by GC with the area normalization method.
The reaction was also optimized for temperature (Table 4). It
was observed that lower temperature was disadvantageous to
oxidation reaction, which greatly prolonged reaction time (Table
4, entries 1-2). Although the best conversion (100%) of oxidation
reaction was given at 30-35 °C (Table 4, entry 3), as temperature
was increased to 35-40 °C, similar result was observed (Table 4,
entry 4). Hence, finally 30-35 °C was chosen for further study.
Table 2 Comparative study with various solvents
Entry
Solvent
Silica
chloride
(mmol)
Oxidant
H2O2
(equiv.)
Time
(min)
Conv.b
(%)
Selectivityb
(%)
2a
1
2
MeCN
MeCN
0.5
0.5
0.5
0.7
30
30
42
61
42
61
Table 4 Influence of reaction temperature
3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
-
0.5
0.5
0.5
0.5
0
0.9
1.0
1.1
0
30
05
05
30
300
30
300
30
30
30
30
30
30
30
30
30
30
85
100
100
0
85
100
100
0
4
Entry
Temperature
Time
(min)
Conv.b
(%)
Selectivityb
(%)
5
(C)
6
2a
7
1.0
0
38
0
38
0
1
2
3
4
20-25
25-30
30-35
35-40
30
30
05
05
55
88
100
100
55
88
100
100
8
0
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
02
93
59
43
52
60
88
73
70
81
87
02
93
59
43
52
60
88
73
70
81
87
10
11
12
13
14
15
16
17
18
19
EtOH
H2O
aReaction conditions: 1a (1 mmol), MeCN (3.0 mL), silica chloride (0.5
mmol), 30% H2O2 (1.0 equiv.), temp. (C), bconversion and selectivity
determined by GC with the area normalization method.
CHCl3
Toluene
EtOAc
THF
Eventually, 1 mmol of substrate, 3 mL MeCN as solvent, 0.5
mmol silica chloride catalyst, 1.0 equiv. of 30% H2O2 as a
oxidant and 30-35 C temperature were found to be the optimized
reaction conditions for this protocol. We also investigated the
substrate scope using various functional groups present on
arylboronic acids (Table 5). Oxidation of arylboronic acid
produced excellent yields of phenol under the optimized reaction
conditions (Table 5, entries 1-17). The phenol formation occurred
in specified time as shown in Table 5. Arylboronic acids with
various electron-withdrawing or electron-donating groups such as
CH3, C6H5, C(CH3)3, 2,3-dimethyl, OCH3, OC4H9, CHO, Cl, Br,
F, CF3, 4-Cl-2-CH3 and NO2 (Table 5, entries 2–14) underwent
oxidation reaction affording excellent yields (95–98%).
DCM
DMF
DMSO
Acetone
aReaction conditions: 1a (1 mmol), solvent (3.0 mL), silica chloride (mmol),
30% H2O2 (equiv.), temp. (30-35 C), bconversion and selectivity determined
by GC with the area normalization method.
In this work, various catalysts were used in oxidation of 1a
(PBA) to 2a with H2O2 as an oxidant and MeCN as a solvent. The
results are given in Table 3. We found that higher conversion was

3
Naphthylboronic acids and heteroarene were also converted to
their corresponding phenols giving excellent yields (Table 5,
entries 15-17).
Table 5 aOxidation of arylboronic acids to phenols
12
13
08
10
97
95
Entry
Substrate
Time
(min)
Yieldb
(%)
1
05
05
05
10
10
98
97
98
97
96
14
15
10
10
97
96
2
3
4
5
16
17
10
10
97
92
aReaction conditions: arylboronic acid (1 mmol), MeCN (3.0 mL), silica
chloride (0.5 mmol), 30% H2O2 (1.0 equiv.), temp. (30-35 C), bIsolated
Yield.
6
7
10
10
10
05
05
97
96
97
98
97
The reaction mechanism for oxidation of phenylboronic acid
is shown in Fig. 1. It shows that silica gel reacts with SOCl2 to
give SC which subsequently then reacts with H2O2 to give silica-
peroxide complex. This complex then further reacts with
phenylboronic acid and undergoes rearrangement to give phenol.
In summary, we have developed a simple, highly efficient,
cheap and environmentally benign methodology for oxidation
of arylboronic acids by using new oxidation system i.e (Silica
chloride, H2O2) with short reaction time and excellent yields.
The preparation of the catalyst is simple and isolation of
products from hetrogenous reaction mixture is easy and not
time consuming. It is noteworthy that various functional
groups present on arylboronic acids were very well tolerated
in this oxidation. Moreover, this protocol is cheap,
convenient, easy to handle and safe. We believe that this
system will surely surpass the previously reported methods.
8
9
10
11
05
97

4
Tetrahedron Letters
Figure 1. Possible mechanism for oxidation of phenylboronic acid
29. Wagh, R. B.; Gund, S. H.; Nagarkar, J, M. J. Chem. Sci.
Acknowledgments
2016, 128, 1321-1325.
30. Typical Procedure for the preparation of silica chloride:
To well-stirred silica gel (20 g) in CH2Cl2 (50 mL) was
added drop wise SOCl2 (20 g) at room temperature.
Evolution of copious amounts of HCl and SO2 occurred
instantaneously. After stirring for 1 h, the solvent was
removed to dryness under reduced pressure. The resulting
white-grayish powder of silica chloride could be stored in
sealed vessels for 6 months without any critical decline in
activity. The amount of chloride in SC (2.6 mmol of Cl per g
silica) is calculated by a standard procedure.27(b)
The author (RBW) is greatly thankful to the UGC (University
Grant Commission, India) for the award of research fellowship.
References and notes
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31. General procedure for the oxidation of arylboronic acids to
phenols (Table 5):
An oven-dried Schlenk flask was allowed to cool to room
temperature and charged sequentially with arylboronic acid (1
mmol), MeCN (3.0 mL) and silica chloride (0.5 mmol). The
reaction was then activated by addition of 30% H2O2 (1.0
equiv.) and stirred at 30-35 °C for the required time
as given in Table 5. The progress of reaction was monitored
by TLC. After complete conversion of starting material, the
reaction mixture was filtered to remove silica gel. The
reaction mixture was neutralized with 5% NaHCO3 solution
(5 mL). Then the product was extracted with ethyl acetate (30
mL) and subsequently washed with distilled water (10 mL).
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was removed under reduced pressure. The resultant product
was purified by column chromatography using silica gel with
n-hexane and ethyl acetate as solvent to get the pure product.
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Supplementary Material
Supplementary material that may be helpful in the review
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file. That file can then be transformed into PDF format and
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5
Highlights





Silica chloride as a heterogeneous catalyst
Cheap, transition metal free approach
Oxidation using green oxidant H2O2
Broad substrate scope
Mild reaction conditions