Electrochemical synthesis of quinones and other derivatives in biphasic medium

Article abstract of DOI:10.1016/j.tetlet.2017.04.099

Electrochemical synthesis of quinones has been attempted from phenols, 1,4-dihydroxybenzenes, 1,4-dihydroxynaphthalenes and related compounds using biphasic media. Excellent yields of quinones (98%) or brominated diols have been achieved with good current efficiency. Reuse of the electrolyte without any modification and quantitative conversion of substrate with theoretical amount of current are the advantages of this method.

Full text of DOI:10.1016/j.tetlet.2017.04.099

Tetrahedron Letters xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Electrochemical synthesis of quinones and other derivatives in biphasic
medium
V.M. Shanmugam, K. Kulangiappar, M. Ramaprakash, D. Vasudevan, R. Senthil Kumar, D. Velayutham,
⇑
T. Raju
CSIR-Central Electrochemical Research Institute, Karaikudi 630 003, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Electrochemical synthesis of quinones has been attempted from phenols, 1,4-dihydroxybenzenes, 1,4-
dihydroxynaphthalenes and related compounds using biphasic media. Excellent yields of quinones
(98%) or brominated diols have been achieved with good current efficiency. Reuse of the electrolyte with-
out any modification and quantitative conversion of substrate with theoretical amount of current are the
advantages of this method.
Received 29 March 2017
Revised 24 April 2017
Accepted 29 April 2017
Available online xxxx
Ó 2017 Elsevier Ltd. All rights reserved.
Keywords:
Biphasic electrolysis
Electrochemical
Quinone
Dialcohol
Phenol
Naphthol
Introduction
Strongly oxidizing quinones include chloranil and 2,3-dichloro-
5,6-dicyano-1,4 benzoquinone (DDQ). 9,10-Anthraquinone-2,7-
Quinones are the largest group of naturally occurring pigments
coloured bright yellow or red. 1,4-Benzoquinone is the basic struc-
ture of quinonoid compounds. They are essential for many life pro-
cesses in that they readily participate in biological redox processes.
For example, the ubiquinones are the essential electron-transfer
agents in our respiratory chain. Doxorubicin is one of the front-line
cancer chemotherapy treatment agent. They function as intermedi-
ates in the biosynthesis of important antibiotics like tetracyclines,
and exhibit a broad spectrum of biological activities with antiox-
idative, cytotoxic, anticancer, antidiabetic and enzyme inhibitory
activities.1–8
The synthesis and study of quinones is therefore of immense
importance given the biological activity associated with many such
compounds, and hence it is an extremely active area of research
worldwide.1–4 Quinones also have importance as intermediates
in organic synthesis and are among the most abundant substruc-
tures found in numerous naturally occurring bioactive mole-
cules.5–7
disulphonic acid (AQDS) a quinone similar to one found naturally
in rhubarb has been used as a charge carrier in metal-free flow
batteries.5
1,4-Benzoquinones are often readily made from reactive aro-
matic compounds with electron-donating substituents such as i)
Phenols with t-butyl hydrogen peroxide/Ru catalyst,9 polymer sup-
ported vanadium salt,10 supported heteropolycompounds,11 potas-
sium peroxomonosulfate catalysed by iron and cobalt
phthalocyanine tetrasulfonate,12 ii) By the selective demethylation
of dimethoxy benzene or hydroquinone dimethyl ether with nitric
acid,13 silver oxide,14 CAN in CH3CN15–28 and with H2O2/methyltri-
oxo rhenium.29 iii) Direct oxidation of aromatic ring compounds to
quinone also reported. For example 2-methylnaphthalene was
quantitatively oxidized to quinones, 2-methyl-1,4-naphtho-
quinone 66% (vitamin-K3) and 6-methyl 1,4-naphthoquinone 34%
using Ce(IV)methanesulphonate as oxidant.30 But the known path-
ways demonstrate disadvantages regarding selectivity and sustain-
ability. iv) By the Oxidation of 1,4-dihydroxybenzene with ceric
ammonium nitrate(CAN),31,32 AgO,33,34 HOCl35 represent a useful
alternative method. The oxidation of hydroquinone is a rapid and
convenient method to get quinone due to formation of single iso-
mer. Recently, Chaturvedi et al. reported the oxidation of phospho-
rylated 1,4-dihydroxynaphthalenes in THF to the corresponding
1,4-naphthoquinones in excellent yields using N-bromosuccin-
2-Alkylanthraquinones are used in the industrial production of
hydrogen peroxide. Benzoquinone is used as an oxidizing agent.
⇑
Corresponding author.
E-mail addresses: traju@cecri.res.in, rajuorganic@yahoo.co.in (T. Raju).
http://dx.doi.org/10.1016/j.tetlet.2017.04.099
0040-4039/Ó 2017 Elsevier Ltd. All rights reserved.
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2
V.M. Shanmugam et al. / Tetrahedron Letters xxx (2017) xxx–xxx
imide (NBS).36 The conventional method has the disadvantages of
handling highly corrosive and costly oxidant and in the case of
NBS, disposal of succinimide is an additional step involved. The
electrochemical oxidation of quinol phosphate has been reported
in aqueous solutions.37 Linjin Ma et al. reported on the oxidation
behaviours and the diffusion mechanism of hydroquinone at pre-
anodized carbon paste electrode by cyclic voltametry.38 Electro
synthesis of benzoquinone from phenol was studied by Abaci
et al.39 by the potentiostatic electrolysis of a CH3CN solution con-
taining 20 mM phenol, 20 mM water, 10 mM HClO4 and 100 mM
TBAP using PbO2 electrode. The maximum efficiency of 61% and
Fig. 2. Reaction set-up for galvanostatic biphasic electrolytic oxidation.
74% of conversion was observed with
a & b-surfaces of the PbO2
electrodes respectively at a potential of 1.6V versus Ag/AgCl. The
benzoquinone decomposition products increased beyond 20 mM
phenol concentration. Though the electrochemical oxidation of
hydroquinone to quinone was examined by cyclic voltammetry
by a number of authors the galvanostatic method was not reported
to the best of our knowledge.40–42
In this communication, we report a convenient method for the
oxidation of 1,4-dihydroxybenzene derivatives to the correspond-
ing 1,4-benzoquinones by the galvanostatic biphasic electrolysis
(Scheme 1). The aqueous NaBr containing H2SO4 present as aque-
ous phase and dichloromethane containing the aromatic diol as
the organic phase. A charge of 2F/mol of the substrate were passed
maintaining the temperature of the reaction mixture at 15 °C for
quinone formation. However, in cases where quinones did not
form, the nuclear brominated products were formed with the pas-
sage of 2 faraday charge and tribromo derivatives were formed as a
single product after passing a charge of 6.5 F/mol.
δ+
o
OH
O
O
-e-
-H+
-e-
-H+
OH
O
O
H
1,4-benzoquinone
1,4-dihydroxybenzene
Scheme 1. General mechanism for the electro chemical oxidation of 1,4-dihydrox-
ybenzene in a biphasic medium.
ventional two phase electrolysis the water insoluble reactant is
present in the lower organic phase and the reactive species gener-
ated the by the electrolysis migrates from upper aqueous phase to
the inter phase for the reaction to occur and the product can be iso-
lated from the organic phase after evaporation of the organic
solvent.
Results and discussion
In this study, oxidation of 1,4-dihydroxybenzene derivatives to
the corresponding 1,4-benzoquinones was investigated by elec-
trolysis in biphasic media. Aqueous NaBr containing H2SO4 is the
upper phase and CH2Cl2 containing 1,4-dihydroxybenzene is pre-
sent in the lower organic phase. The electrolysis was carried out
at 15 °C. During the electrolysis the substrate gets oxidised at the
anode surface with the theoretical amount of current.43 In the con-
The advantage of the present method is that the utilization of
theoretical amount of current for quantitative conversion of the
substrate due to the existence of water soluble substrate (1,4-dihy-
droxybenzene) near the vicinity of electrode in the upper aqueous
phase and the migration of the product to the more soluble organic
phase avoids the over oxidation of highly reactive quinones. After
removal of the product from the organic phase, the aqueous elec-
trolyte could be reused several times for further synthesis of qui-
nones or the nuclear brominated products as the case may be.
The possible reaction mechanism for the oxidation of 1,4-dihy-
droxybenzene is given in the Scheme 1. Initially water soluble 1,4-
dihydroxybenzene forms a phenoxy radical (HOC6H4OÅ) at the
vicinity of anode followed by the rearrangement of electrons to
remove a proton from another phenolic group.
HOC6H4OH ! HOC6H4OÅ þ Hþ þ 1eꢀ
HOC6H4OÅ ! C6H4O2ðbenzoquinoneÞ þ Hþ þ 1eꢀ
The results on the electrochemical oxidation of aromatic diols
using biphasic electrolysis are shown in Table 1. It has been shown
that benzoquinone can be prepared with high efficiency from
hydroquinone in 89–99% yield with >99% conversion. It can be seen
that reactant 1–5, wherein the alcoholic groups present in 1,4-
position, yielded quinones, i.e. 1,4-benzoquinone or 1,4-naphtho-
quinone as the case may be with yields in the range of 94–97% with
high current efficiencies. However with reactant 6 (9,10-dihydrox-
yanthracene), no reaction occurred due to the quinol ring being
highly deactivated due to adjacent benzene rings in either direc-
tion and hence resistant to oxidation. Whereas the reactant 7 to
9 (catechol and resorcinol), the corresponding bromo derivatives
were formed as the products, instead of quinones with the passage
of 2 F of charge. This is mostly probably due to steric effect which
prevents quinone formation. With reactant 10, bromination occurs
Fig. 1. Electrochemical cell for galvanostatic biphasic electrolytic oxidation.
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V.M. Shanmugam et al. / Tetrahedron Letters xxx (2017) xxx–xxx
3
Table 1
Electrochemical preparation of quinones by biphasic electrolysis.a
Entry Reactant
Product
Charge passed (F/mole) Yieldb (%) Current efficiencyc (%)
1
2
99
99
OH
O
OH
O
O
2
2
99
99
OH
Cl
Cl
OH
O
3
4
2
2
98
99
98
99
OH
O
O
O
OH
OH
CH3
CH3
O
OH
5
2
98
98
O
OH
Br
Br
Br
Br
O
O
OH
OH
6
4
0
0d
OH
O
7
8
2
95
90
95
83
OH
OH
Br
Br
OH
OH
OH
OH
6.5
Br
OH
OH
Br
OH
9
2
95
95
OH
Br
OH
OH
(continued on next page)
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V.M. Shanmugam et al. / Tetrahedron Letters xxx (2017) xxx–xxx
Table 1 (continued)
Entry Reactant
10
Product
Charge passed (F/mole) Yieldb (%) Current efficiencyc (%)
10 95 76
Br
CH3
CH3
Br
CH3
CH3
HO
OH
HO
OH
Br
Br
a
Reaction conditions: Anode: platinum, Cathode: Platinum, Electrolyte: NaBr + H2SO4, Current density = 30 mA/cm2, Temperature = 15 °C.
Isolated yield.
Current efficiency = Ratio of the experimental yield to the theoretical yield.
Starting material recovered.
b
c
d
successively and a final compound of 2,20,6,60-tetra bromo-4,40-iso-
propylidene diphenol was formed as a single product in 94% yield.
The mechanism for the electrochemical bromination of aromatic
compounds is known in literature.44
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Conclusions
Quinones can be quantitatively synthesised with high current
efficiencies from the corresponding 1,4-dihydroxybenzene deriva-
tives through galvanostatic biphasic electrolytic oxidation. How-
ever in the case of 1,2 and 1,3-dihydroxybenzene derivatives,
only the bromination reaction occurred to yield the corresponding
bromo derivatives.
The advantages of these biphasic electrochemical oxygenations
are i) the pH of the electrolyte is not changed since the protons
released during the oxidation are driven out as hydrogen gas at
the cathode. Hence the electrolyte is available for reuse without
any loss of its constituents. ii) theoretical amount of current gives
the product in quantitative yield (85–99%), iii) Simple work up of
the reaction mixture.
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A. Supplementary data
43. Experimental procedure: All the chemicals employed in this work were of AR
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2017.04.
099.
grade and procured from
E Merck. Melting points of the synthesized
compounds were checked in open capillary tubes by using a digital auto m.p
apparatus and found uncorrected. All the reactions were monitored by HPLC
using 100% acetonitrile as eluent with a 254 nm UV lamp as a detector.
Deionised water was used for preparation of all solutions. All the compounds
were characterised by FTIR (Paragon 500) using KBr pellets, 1H NMR
spectroscopy in CDCl3 (500 MHz, Bruker) and 13C NMR spectroscopy in CDCl3
(125 MHz, Bruker) using TMS as internal standard. Electrochemical
experiments were carried out using APLAB power source.General procedure
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