Bio-based green solvent for the catalyst free oxidation of arylboronic acids into phenols

Article abstract of DOI:10.1039/c5ra18080e

A bio-based green solvent, lactic acid, is found to be an efficient reaction medium for the catalyst free oxidation of arylboronic acids into phenols with aqueous hydrogen peroxide. Various substituted arylboronic acids have undergone ipso-hydroxylation smoothly at room temperature to provide corresponding phenols in excellent yields. Remarkably, the oxidation susceptible functional groups such as sulphide, ketone, aldehyde and olefin are tolerated under the reaction conditions. Over all, lactic acid showed higher efficiency as a solvent medium when compared with conventional acetic acid.

Full text of DOI:10.1039/c5ra18080e

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A bio-based green solvent, lactic acid is found to be an efficient reaction medium for the catalyst free oxidation of aryl
boronic acids into phenols with aqueous hydrogen peroxide.

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Bio-based green solvent for the catalyst free oxidation of
arylboronic acids into phenols
Received 00th January 20xx,
Accepted 00th January 20xx
b
Surabhi Gupta,a# Priyanka Chaudhary,a# Lavudi Seva,b Shahulhameed Sabiah and Jeyakumar
Kandasamya*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A bio-based green solvent, lactic acid is found to be an efficient expensive non-bio based green solvents in organic synthesis.10-12
reaction medium for the catalyst free oxidation of arylboronic
acids into phenols with aqueous hydrogen peroxide. Various Glycerol, a by-product obtained from triglycerides during the
substituted arylboronic acids have undergone ipso-hydroxylation biodiesel production, is already explored as a green solvent in many
smoothly at room temperature to provide corresponding phenols organic reactions.13,14 Other bio-based solvents such as 2-
in excellent yields. Remarkably, the oxidation susceptible methyltetrahydrofuran, ethyl lactate, ɤ-valerolactone, D-limonene,
functional groups such as sulphide, ketone, aldehyde and olefin p-cymene and fatty acid methyl esters (FAMEs) are now
are tolerated under the reaction conditions. Over all, lactic acid significantly replacing the hazardous petroleum solvents in many
showed higher efficiency as a solvent medium when compared organic synthesis.4-12 In addition, eutectic mixture of various
with conventional acetic acid.
biomass derived chemicals or solvents (example: eutectic mixture
of glycerol, levulinic acid, carbohydrates, gluconic acid, etc.) have
Solvents play an important role in organic synthesis while in some found selective applications in organic synthesis as well as in
cases solvents itself drive the reaction without any catalysts.1 Such pharmaceutics.15-18
kind of catalyst free organic reactions offer several advantages like
reduced environmental pollutions, uncomplicated experimental and
workup procedures, simple purification steps, etc.2, 3 Therefore, the
catalyst free organic transformations have received more attention
in recent years. On the other hand, “green solvents” have been
focused in the past few decades in order to minimize the
environmental pollution resulting from the use of hazardous
solvents in chemical production.4-7 Green solvents have been
majorly characterized by their level of toxicity, volatility, reusability,
stability, flammability, bio-degradability and renewability.8, 9 In the
past decade, water, supercritical CO2, ionic liquids, organic
carbonates, fluorous compounds and polyethylene glycol (PEG)
were identified as green solvents and efficiently used in organic
synthesis (Figure 1, A).4-9 Recently, bio-based solvents which are
produced from renewable sources have received much attention
due to their sustainability and eco-compatibility (Figure 1, B).10
From environmental point of view, bio-based solvents are also
considered as green solvents which could be an alternative not only
to the conventional petroleum based solvents, but also to the
a.Department of chemistry, Indian Institute of Technology (BHU), Varanasi, Uttar
Pradesh-221005; Email: jeyakumar.chy@iitbhu.ac.in
b.Department of chemistry, Pondicherry University, Pondicherry-605014
# Both authors contributed equally to this work
Figure 1. Structures of various green and bio-based solvents used in
organic synthesis.
† Electronic Supplementary Informaꢀon (ESI) available: See
DOI: 10.1039/x0xx00000x
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J. Name., 2013, 00, 1-3 | 1
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Phenolic compounds have found wide applications in various fields have tested the reaction in acetic acid and fortunatelVyietwhAertriceleaOctniloinne
like medicines, cosmetics, food industry, materials and polymers, leads to completion in 15 minutes to yield D9O5I%: 10o.f1043-9c/hClo5RroAp18h0e8n0oEl
etc (Figure 2).19-24 There are different approaches for the (Table 1, entry 10). Despite the efficiency, acetic acid (glacial) is
preparation of phenolic compounds which includes i) nucleophilic corrosive, and its vapor irritates the eyes, produces a burning
substitution of aryl halides with hydroxyl nucleophile, ii) sensation in the nose, and can lead to a sore throat and lung
diazotization of aromatic amines followed by aqueous hydrolysis, iii) congestion.39 Moreover, about 75% of the acetic acid used in the
CH-oxidation of aryl rings and iv) oxidative hydrolysis of arylboronic industry is currently produced through chemical methods. 40, 41
acids.25 Synthesis of phenols from arylboronic acids is becoming
more preferable as compared to other methods due to ready Table 1. Oxidation of 4-chlorophenylboronic acid in various solvents
availability, low toxicity and high stability (toward heat, air and with hydrogen peroxide.a
moisture) of arylboronic acids.26 Therefore, recently numerous
methods have been developed for the oxidative conversion of
arylboronic acids into phenols using transition metals, hydrogen
peroxide with different catalysts, hypervalent iodine reagents, N-
oxides, photo catalysts and electrochemical techniques.27-38 The
common problems associated with majority of these reports are the
use of harsh reaction conditions,36 non-ecofriendly solvents34, high
reaction temperature,36 longer reaction time,33 excess oxidants,27,
28, 35
30, 34
non-commercially available catalysts or oxidants,29,
etc.
Therefore, the development of simple, efficient and greener
method is still in demand and we have directed our studies towards
finding a suitable catalyst free system for the oxidative conversion
of arylboronic acids into phenols using green oxidant aqueous
hydrogen peroxide.
aReaction conditions: Substrate (0.5 mmol), Solvent (1 mL), H2O2 (1.0 equiv.), stirred at
RT. b Isolated Yield
Lactic acid is a biomass derived weak acid widely used in the food,
43
agricultural, textile, pharmaceutical and cosmetic industries.42,
However, lactic acid is less explored as a solvent in organic synthesis
while acetic acid have found wide applications. In contrast with
acetic acid, lactic acid is a nontoxic and odorless liquid produced
through the safer fermentation method from carbohydrates
(Scheme 1).43,44 The pKa, density and boiling point of lactic acid is
Figure 2. Applications of phenolic compounds in different fields.
3
°
3.7, 1.20 g/cm and 120 C, respectively, which is comparable with
At the outset, 4-chlorophenylboronic acid was chosen as a model
substrate and oxidized with 1.0 equivalent of 30% aqueous
hydrogen peroxide in various solvents such as methanol, ethanol, t-
butanol, water, tetrahydrofuran (THF), acetonitrile, toluene,
glycerol and acetic acid (Table 1). Among the polar protic solvents,
methanol provides the maximum yield of 4-chlorophenol, i.e. 41%
after 60 minutes (Table 1, entry 1) while other protic solvents such
as ethanol, t-BuOH, glycerol and water gave relatively lower yields
(Table 1, entries 2-5). It is also important to note that even after
prolonged reaction time (12 h) full conversion of boronic acid into
phenol was not observed in methanol (Table 1, entry 6). Further,
the oxidation reaction was carried out in polar aprotic solvents such
as THF, acetonitrile and toluene (Table 2, entries 7-9). The
maximum yield of 42% was observed in acetonitrile while THF and
toluene provide less than 40% of the desired product. Finally, we
3
°
acetic acid (pKa. 4.7, d: 1.05g/cm and bp.117 C) and therefore we
anticipate that lactic acid can be a suitable alternative to the acetic
acid.45 Recently, Yanlong Gu group has demonstrated the first
application of lactic acid as a green solvent for multi-component
reactions (MCR) with several advantages like reusability of the
reaction medium, high efficiency, easy isolation of products, etc.45
Impressed by the above work, we have carried out the oxidation
reaction in lactic acid and pleased to see the quick and clean
conversion of 4-chlorophenylboronic acid into 4-chlorophenol in
good yield (Table 1, entry 11). Encouraged, we have further studied
the oxidation of various functionalized arylboronic acids not only in
lactic acid, but also in acetic acid in order to compare the efficiency
of the reaction mediums. The results obtained are summarized in
Table 2.
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Scheme 1. Lactic acid from biomass.
Table 2. Oxidation of various functionalized arylboronic acids in lactic acid and acetic acid.a
aReaction conditions: Substrate (0.5 mmol), Solvent (1 mL), H2O2 (1.0 equiv.), stirred at RT; Isolated yield is shown in the table.
bLactic acid is used as solvent. cAcetic acid is used as solvent. d1,4-phenylenediboronic acid is used as a substrate with 2.5 equiv. H2O2.
The un-substituted arylboronic acids such as phenylboronic acid, while acetic acid required about 15 minutes. Nevertheless, both
and α, β-naphthylboronic acids were converted into corresponding solvents gave the desired products in excellent yields.
phenol and naphthols (Table 2, 2a-2c) within 5 minutes in lactic acid Subsequently, the oxidation of methoxy, methyl, ethyl, tertiary
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butyl, phenyl, nitro, fluoro, chloro and iodo substituted
phenylboronic acids were tested in order to establish a general
applicability of this methodology in complex synthesis (Table 2, 1d-
1q). All these substrates underwent ipso-hydroxylation smoothly
irrespective of electronic properties of the arylboronic acids and
desired products were obtained up to 97% yield (Table 2, 2d-2q).
Similarly, 1,4-phenylenediboronic acid was oxidized to
hydroquinone in quantitative yield with 2.5 equivalent of hydrogen
peroxide (Table 2, 2r). Further to extend the scope of this
methodology, oxidation of 4-acetyl phenylboronic acid (a substrate
which can undergo Baeyer-Villiger oxidation) was examined in both
lactic acid and acetic acid medium. Remarkably, ketone functional
group was found to be very stable during the oxidation and gave 4-
acetyl phenol in 95% yield in both solvents (Table 2, 2s). Over all,
lactic acid was found to be very efficient solvent medium for the
oxidative ipso-hydroxylation reaction when compared with acetic
acid.
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DOI: 10.1039/C5RA18080E
Scheme 4. Oxidation of various sensitive functional groups with
lactic acid.
Although the exact mechanism of the reaction is unclear, two
possible mechanistic pathways (A and B) are shown in Scheme 5.
According to pathway A, the first step would be the formation of
peracid (peracetic/perlactic acid) which is generally known as more
reactive species than simple hydrogen peroxide.46 The resulted
peracid reacts with arylboronic acid to provide boronate ester
which is further hydrolyzed to phenol and boric acid in the presence
of water (Scheme 5, A).37 On the other hand, the oxidation may
involve the electrophilic attack of the hydrogen peroxide on boron
followed by protonation of the peroxide by the acetic acid or lactic
acid.28 Subsequent migration of the aryl group from boron to
oxygen generates boronate ester which is further hydrolyzed to
phenol by water (Scheme 5, B). However, we believe that the
acidity of the reaction medium would play an important role in the
oxidation reaction. Because, lactic acid (pKa: 3.7) is relatively more
acidic than acetic acid (pKa: 4.7) and it could be a reason for the
enhanced activity of lactic acid over acetic acid.
Scheme 2. Oxidation of phenylboronic acid pinacol ester and
potassium phenyltrifluoroborate in lactic acid.
Similar to arylboronic acids, other surrogates such as phenylboronic
acid pinacol ester and potassium phenyltrifluoroborate were
successfully converted to phenol in a short time (Scheme 2). In
addition, alkylboronic acids such as 2-phenylethylboronic acid (1t)
and cyclohexylboronic acid (1u) were oxidized to corresponding
alcohols in good yields with equal efficiency (Scheme 3).
1.1 equiv. H2O2
OH
Lactic acid
B
R OH
R
OH
30 min, RT
2t
(94%)
1t or 1u
R=
2u
(86%)
Scheme 3. Oxidation of alkylboronic acids with hydrogen peroxide
in lactic acid.
Further, to test the functional group tolerance, a series of
competition experiments were conducted between phenylboronic
acids and oxidation susceptible functional groups. The study reveals
that sulfide, aldehyde and olefin functional groups are tolerated
under the reaction condition while phenylboronic acid was
selectively converted into phenol (Scheme 4).
Scheme 5. Two different mechanistic pathways (A and B) for the
oxidation reaction.
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J.K gratefully acknowledges IIT (BHU) for the start-up research
grant. S.G and P.C acknowledges IIT (BHU) for a research fellowship.
J.K thanks to Dr. K. Murugan (Yung Shin, Taiwan) for a helpful
discussion during the manuscript preparation. J.K also
acknowledges Prof. V. Srivastava (IIT BHU) for a helpful discussion
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