Cellulose as recyclable organocatalyst for ipso-hydroxylation of arylboronic acids

Article abstract of DOI:10.1016/j.tetlet.2019.151044

Cellulose catalyzed oxidative hydroxylation of aryl and hetero-arylboronic acids to the corresponding phenols under metal and base free strategy has been demonstrated. The sustainable ipso-hydroxylation takes place using hydrogen peroxide as an oxidant in water under mild condition in shorter period of time. Interestingly, easy recovery and reusability of heterogeneous catalyst without significant loss in catalytic yield makes the protocol environmentally benign.

Full text of DOI:10.1016/j.tetlet.2019.151044

Tetrahedron Letters 60 (2019) 151044
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Tetrahedron Letters
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Cellulose as recyclable organocatalyst for ipso-hydroxylation of
arylboronic acids
⇑
Khairujjaman Laskar, Subham Paul, Utpal Bora
Department of Chemical Sciences, Tezpur University, Napaam 784028, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Cellulose catalyzed oxidative hydroxylation of aryl and hetero-arylboronic acids to the corresponding
phenols under metal and base free strategy has been demonstrated. The sustainable ipso-hydroxylation
takes place using hydrogen peroxide as an oxidant in water under mild condition in shorter period of
time. Interestingly, easy recovery and reusability of heterogeneous catalyst without significant loss in
catalytic yield makes the protocol environmentally benign.
Received 27 June 2019
Revised 10 August 2019
Accepted 12 August 2019
Available online 13 August 2019
Ó 2019 Elsevier Ltd. All rights reserved.
Keywords:
Cellulose
Green synthesis
Ipso-Hydroxylation
Phenol
Introduction
tion. Various protocols for ipso-hydroxylation of arylboronic acids
were put forwarded using different catalysts such as mont K-10
Phenols and their derivatives have been found to an integral
part of numerous natural products [1].
supported AgNPs-H2O2 [17], biosilica-H2O2 [18], mont-KSF encap-
sulated Co(OH)x catalyzed [19], I2-H2O2 [16], Al2O3-H2O2 [20],
CuSO4-phenanthroline [21], CuNP [22], TBHP [23] amberlite
IR-120 resin [24], lactic acid-H2O2 [25], Polymer supported Pd-Ag
hybrid [26] etc. Although majority of these protocols found to be
effective in conversion of phenol through ipso-hydroxylation of
arylboronic acid but mostly lacking ‘‘Greener”’ procedure other-
wise uses excess oxidizing agent, volatile organic solvents, higher
temperature, base, metal catalysts etc. Thus, the development of
a metal and base free and environmentally benign procedure for
the ipso-hydroxylation is more viable alternative to be explored
[27]. However, the use of organocatalyst for transformations has
carried the attention of the researchers from the point of view of
green catalyst, easily available, less expensive and economically
sustainable.
In recent years, ‘‘Green Chemistry” has emerged as major con-
cern for the development of new synthetic methodologies in mod-
ern chemistry perspective. The design of new route with green
procedure has attracted especially in the areas of organic synthesis,
drug discovery and material sciences [28–31]. Cellulose, an inex-
haustible natural polymeric material, endowed with a polyfunc-
tional macromolecular structure and an environmentally benign
nature, has attracted wide attention in various branches of chem-
istry, remarkably in the development of new sustainable heteroge-
neous catalyst [32–34]. Cellulose has an unusual structure in
which every other monomer subunit is upside down. This gives
it some extraordinary physical and chemical properties, because
They act as vital intermediates and building blocks for the
synthesis of pharmaceuticals, polymers and naturally occurring
compounds [2–4]. Natural phenolic compounds exhibit a broad
range of biological activities [4]. Phenolic compounds have privi-
leged scaffold in prevention as well as treatment of various dis-
eases (Fig. 1) [5–8]. The direct hydroxylation to establish mild
and efficient access of aromatic motif to corresponding phenols is
of great significance in synthetic chemistry. The traditional method
for the preparation of phenol involves Dow’s process and Hock’s
process but results low yield [9]. Besides, this using aryl halide as
precursor for the phenol synthesis have also suffered from harsh
condition and additional purification steps [10,11]. In this context
researchers have found arylboronic acid a new avenue for substi-
tuting the existing inactive synthetic precursors. The significant
attention gained by arylboronic acid in various organic transforma-
tions due to their versatile nature, structural diversity, low toxicity,
easy availability, greater stability, and reactivity [12–14].
Investigation showed that arylboronic acids can be easily con-
verted into corresponding phenols by oxidative hydroxylation
[15,16], upon careful control on the amount of oxidants and reac-
tion time and it is worth mentioning from previous years that
efforts have been made to obtain phenols through ipso-hydroxyla-
⇑
Corresponding author.
E-mail addresses: utbora@yahoo.co.in, ubora@tezu.ernet.in (U. Bora).
https://doi.org/10.1016/j.tetlet.2019.151044
0040-4039/Ó 2019 Elsevier Ltd. All rights reserved.

2
K. Laskar et al. / Tetrahedron Letters 60 (2019) 151044
Fig. 1. Structure of phenolic compound used in late clinical research.
adjacent cellulose molecules bind readily into sheets and fibres.
The lack of solubility in most organic solvents emanate from its
supramolecular architecture and the natural abundance of this
biopolymer makes it a promising supporting catalyst in various
organic transformations [35]. Very recently, Kim et al. had reported
chitosan as a biopolymer catalyst for ipso-hydroxylation of aryl-
boronic acids to corresponding phenols [36]. However, chitosan
production warrants its derivation from its natural source chitin
[37]. In contrast, cellulose being nature’s most abundant polymer
offers greater abundance and direct utilization without any neces-
sary pre-production from natural sources. Therefore, use of cellu-
lose as a biopolymer holds significance in terms of availability
and applicability. In view of aforementioned facts and with the
concept of sustainable development, here we used cellulose as a
biopolymer catalyst for the hydroxylation of arylboronic acids
under benign reaction condition.
column chromatography on silica gel (EtOAc/ hexane) to obtain the
desired product.
Results and discussion
To understand/examine the catalytic applicability of cellulose in
ipso-hydroxylation, phenylboronic acid (1a) was choosen as a
model for screening the suitable reaction conditions, and the
results are summarized in Table 1. All the reactions were per-
formed at room temperature with cellulose (10 mg) and H2O2
(0.5 mL) using various solvents. Initially, the investigation was
done without using any oxidant and no conversion was observed
even after prolonged stirring (entry 1, Table 1). However, when
reaction was performed in the absence of cellulose the correspond-
ing product (2a) was obtained in low yield (entry 2 and 3, Table 1)
[17,24]. Moreover, excellent results were obtained with the reac-
tion involving a combination of H2O2 and cellulose under the same
conditions (entry 4, Table 1). The effect of amount of H2O2 used in
the present protocol was also investigated (entry 5, Table 1). Then
we examined the impact of the cellulose catalyst used in the reac-
tion by decreasing the amount to 5 mg shows a slight decrease in
the yield of phenol suggesting more amount of catalyst was
required for the reaction (entry 6, Table 1). However, increase in
the amount of biopolymer catalyst does not improve the yield of
phenol (entry 7, Table 1). Encouraged by the interesting results,
we then screen the effect of various solvents (2 mL) on the reaction
using 10 mg of catalyst. Among the solvents screened, in polar sol-
vents such as methanol, ethanol, isopropyl alcohol, hydroxylation
takes place smoothly with good yield (entries 8–12, Table 1). On
the other hand to understand the role of solvents towards cellulose
catalysed ipso-hydroxylation, experiments were performed with
aprotic solvents (CH3CN, CH2Cl2 and THF) results 65–72% yield
(entries 13–15, Table 1).
Experimental
Materials
All the chemicals were purchased from Sigma Aldrich, India and
are of analytical grades. The details of characterization techniques
are discussed in Supplementary Information (SI).
General procedure for ipso-hydroxylation of arylboronic acids
A mixture of arylboronic acid (0.5 mmol), 10 mg cellulose
(15 wt%) and 2 mL distilled H2O were taken in an oven dried
10 mL round bottomed flask. To this 30% aqÁH2O2 (0.5 mL) was
added dropwise and stirred at room temperature for 5 min. After
completion of the reaction (monitored by TLC), aqueous layer
was centrifuged to recover the catalyst for further use. The prod-
ucts were extracted with EtOAc (3 Â 10 mL), dried with anhydrous
Na2SO4 and then vacuum dried. The crude product was purified by
With standard reaction condition, it can be understand that the
assistance of cellulose with H2O2 as oxidant as an adaptable

K. Laskar et al. / Tetrahedron Letters 60 (2019) 151044
3
Table 1
Optimization of cellulose catalysed ipso-hydroxylation.a
Entry
Cellulose (mg)
H2O2
Solvent (2 mL)
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
10.0
–
–
10.0
10.0
5.0
15.0
10.0
10.0
10.0
10.0
10.0
10.0
10.0
10.0
–
H2O
–
H2O
H2O
H2O
H2O
H2O
MeOH
EtOH
60
60
60
5
5
5
5
5
5
5
–
8
0.5 mL
0.5 mL
0.5 mL
0.25 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
15
97
89
93
97
88
83
79
84
80
72
65
70
9
10
11
12
13
14
15
iPrOH
MeOH: H2O (1:1)
EtOH: H2O (1:1)
CH3CN
CH2Cl2
THF
5
5
5
5
5
a
Reaction condition: Phenylboronic acid (0.5 mmol), H2O2 (30% aq), 15 wt% of cellulose catalyst.
Isolated yield.
b
alternative course for ipso-hydroxylation of arylboronic acids. Next
to evaluate the scope and limitation of current procedure, we
investigated the scope of our protocol with a series of electroni-
cally diverse arylboronic acids subjected to the oxidative hydroxy-
lation and the results are summarized in Table 2. It has been
observed that both electron-rich and electron-deficient arylboronic
acids resulted corresponding ipso-hydroxylated product in good to
excellent yield which suggests that the electronic nature of
attached substituent has little influence on reaction process. Aryl-
boronic acid with substituent such as Et, OMe, F, Cl, CN, NO2, t-
Butyl, COMe at para position afford excellent yield (2b-i, Table 2)
of substituted phenol irrespective of their electronic nature. Meta
substituted arylboronic acid also gives the product in excellent
yield under the current reaction conditions (2j-n, Table 2). It is
Table 2
Cellulose catalysed ipso-hydroxylation of boronic acidsa
a
Reaction conditions: arylboronic acid (0.5 mmol), 30% aqÁH2O2 and 10 mg of cellulose in 2 mL of water at room
temperature; bIsolated yield; cIsolated yield when the reaction was carried with 1 g of 1a.

4
K. Laskar et al. / Tetrahedron Letters 60 (2019) 151044
Table 3
Comparison of recent catalyst with cellulose for ipso-hydroxylation utilizing H2O2 as an oxidant
Sl. no
Catalyst
Solvent
Time (min)
Temp (oC)
Yield (%)
Refs.
1
2
3
4
5
6
7
8
9
10
Biosilica
Iodine
WERSA
Mont K-10@AgNPs
PEG-400
Cu2O NP
Chitosan
Silica chloride
Pd-Chit-CNT
Cellulose
H2O
–
H2O
–
–
–
H2O
MeCN
–
5
45
5
15
10
10
10
5
rt
rt
rt
rt
rt
rt
rt
35
rt
rt
93
93
98
92
97
96
98
100
95
97
[18]
[16]
[38]
[17]
[39]
[40]
[36]
[41]
15
5
[42]
This work
H2O
noteworthy to observe that heteroaryl boronic acid such as thio-
phene-2-boronic acid and 6-methoxypyridyl boronic acid were
successfully underwent ipso-hydroxylation with good yield (83%
and 87%) respectively (2q and 2r, Table 2), although excellent yield
were observed for hetero-boronic acid to their corresponding alco-
hols (2o, 2p and 2 s, Table 2). Thus the developed protocol is highly
tolerant towards wide range of substituted arylboronic acid func-
tionalities at room temperature, which shows the wide synthetic
utility.
In order to investigate whether our protocol could be upscale to
the gram-level, we performed gram-scale reaction of 1a (1.0 g,
8.19 mmol) under the optimized reaction conditions and results
showed reaction proceeded without any significant loss in effi-
ciency affording 0.717 g of 2a (93%) (Table 2). Thus, the results
showed the potential effectiveness of this process for the high-
yielding synthesis of phenols.
The comparison of cellulose catalyzed ipso-hydroxylation of
arylboronic acid with the existing catalytic systems are well illus-
trated in Table 3, which reveals the advantage of nature friendly
cellulose polymer for the presented hydroxylation reaction.
To expand the scope of our system, similar to arylboronic acids
other surrogates such as potassium phenyltrifluoroborate and
phenylboronic acid ester (3a, 4a and 5a) were hydroxylated
smoothly affording the desired product (2a) in good yield
(Scheme 1).
Reaction mechanism
A plausible mechanistic pathway has been proposed based on
reported literature [18,36]. Cellulose being a polysaccharide, con-
sists of linearly linked
a-D-glucose units containing primary and
secondary hydroxyl groups. These hydroxyl groups of cellulose
form hydrogen bonds with hydrogen peroxide to enhance its
nucleophilicity, which is mainly responsible for the catalytic activ-
ity of cellulose [36]. It is assumed that initially cellulose react with
H2O2 (30% aqueous) to form cellulose-peroxide adduct A via hydro-
gen bonding (Scheme 2). Consequently A interacts with phenyl-
boronic acid (1a) resulting formation of adduct B, which
rearranged and subsequent water loss gave adduct C. Hydrolysis
of C afford the phenol (2a).
Scheme 1. Oxidation of phenylboronic acid ester and phenyltrifluoroborate.
Catalyst reusability
Reusability of any catalyst makes it even more attractive [43].
Although cellulose catalysed efficiently ipso-hydroxylation, the
heterogenesity and sustainability have been proved by its reusabil-
ity. Cellulose catalyzed ipso-hydroxylation of 1a under optimal
condition. After 1st cycle, the catalyst was filtered and washed sev-
eral times with Et2O followed by H2O. The recovered bio-catalyst
was dried in oven at 80 °C for overnight and was further used as
catalyst for the ipso-hydroxylation of arylboronic acids. It was
found that the catalyst maintained good activity for a minimum
of five cycles (Table 4). FT-IR spectra and P-XRD analysis (Figs. S1
and S2) further revealed that the structure of the catalyst does
not alter during the course of the reaction.
Scheme 2. Plausible mechanism for ipso-hydroxylation of phenylboronic acid.
Table 4
Reusability test for cellulose for the synthesis of phenol.
Run
1st
97
2nd
96
3rd
93
4th
93
5th
88
Yield (%)
aReaction condition: Phenylboronic acid (0.5 mmol), H2O2 (30% aq), cellulose (10 mg), H2O (2 mL); bIsolated yield

K. Laskar et al. / Tetrahedron Letters 60 (2019) 151044
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Acknowledgements
K. Laskar is grateful to the DST-SERB, New Delhi, India for pro-
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Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.2019.151044.
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