Dimerization of phenols and naphthols using an aqueous sodium hypochlorite

Article abstract of DOI:10.1016/j.tetlet.2010.02.173

The observation of an unusual dimerization of phenols and naphthols using a sodium hypochlorite (NaOCl) in an aqueous solution is reported. NaOCl is an environmentally friendly and less expensive reagent than previously used reagents for dimerization. The yield of the dimer is moderate to high at ambient temperature.

Full text of DOI:10.1016/j.tetlet.2010.02.173

Tetrahedron Letters 51 (2010) 2497–2499
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Tetrahedron Letters
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Dimerization of phenols and naphthols using an aqueous sodium hypochlorite
Ramesh Neelamegam a, Matthew T. Palatnik c, James Fraser-Rini c, Mark Slifstein a,c
,
Anissa Abi-Dargham a,b,c, Balu Easwaramoorthy a,c,
*
a Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
b Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
c Division of Translational Imaging, New York State Psychiatric Institute, 1051, Riverside Drive, Unit 31, New York, NY 10032, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The observation of an unusual dimerization of phenols and naphthols using a sodium hypochlorite (NaO-
Cl) in an aqueous solution is reported. NaOCl is an environmentally friendly and less expensive reagent
than previously used reagents for dimerization. The yield of the dimer is moderate to high at ambient
temperature.
Received 30 October 2009
Revised 25 February 2010
Accepted 26 February 2010
Available online 3 March 2010
Published by Elsevier Ltd.
Keywords:
Dimer
Phenols
Naphthols
Sodium hypochlorite
1. Introduction
pensive and eco-friendly reagent, brought an aqueous sodium
hypochlorite (NaOCl) to the researcher’s attention.16–21 NaOCl have
The synthesis of symmetrical biaryl compounds is a challenging
and continuously evolving field in organic chemistry. Symmetrical
biaryl compounds are frequently found in natural products chem-
istry and in drug development.1 Recently, there has been numerous
reports in this area, particularly with respect to the dimerization of
phenols and naphthol via an oxidative coupling of monomers using
stoichiometric oxidants as well as relatively complex homoge-
neous and heterogeneous Lewis acid type catalysts.2–4 The use of
Cu(II)–amine complexes,5 Cu(II)–amine complexes with AgCl,6 Cu-
Cl(OH), TMEDA,7 CuSO4(Al2O3),8 K3[Fe(CN)6],9 Mn(acac)3,10,11 and
oxovanadium complexes12 are some notable examples for a cata-
lytic oxidative coupling of 2-naphthols into 1,10-bi-2-naphthols.
The dimerization has also been reported in (a) enzymes such as
horseradish peroxidase13 and laccase14 catalyzed dimerizations
and (b) chloramine induced oxidative dimerization.15
Currently, there are several methods available for the synthesis
of dimers. However, these methods have limitations and disadvan-
tages, such as (1) use of expensive oxidants, (2) use of hazardous
organic solvents, and (3) not suitable for scale-up. Thus, the
replacement of known synthetic routes by environmentally benign
reaction conditions is one of the major goals of Green Chemistry,
which presents both economic and environmental advantages.
Such an attempt, to evolve a novel synthesis route utilizing inex-
been widely used in organic synthesis, including, N-chlorination of
indole,22 intramolecular oxidative coupling of brominated 2,40-
dihydroxy-diarylmethanes, biogenetic synthesis of thelepin,23
and chlorination of various aromatic systems.24 NaOCl has been
successfully used as a reagent for various synthetic conversions,
however, there are no reports of this reagent being used for dimer-
ization of aromatic systems. In this Letter, we report the dimeriza-
tion of various phenol derivatives and naphthol using an aqueous
NaOCl at high yields using ambient conditions. All the reactions re-
ported were carried out with a short reaction time at room
temperature.
2. Results and discussion
Hopkins and Chisholm24 reported the synthesis of 5-chloro-2-
hydroxy-4-methoxybenzaldehyde by chlorination of 2-hydroxy-
4-methoxybenzaldehyde using NaOCl in the presence of 4% aque-
ous NaOH. Under the same reaction conditions, we attempted to
synthesize 3-chloro-2-hydroxy-4-methoxybenzaldehyde by chlo-
rination of 2-hydroxy-5-methoxybenzaldehyde. However, the
reaction did not proceed to afford the expected product. Instead,
the 2-hydroxy-5-methoxybenzaldehyde underwent an unusual
dimerization to produce compound 2a (Scheme 1). Mass spectrom-
etry and NMR confirmed the dimer.25,26 The 1H NMR results of di-
mer 2a showed a doublet of doublet at d 7.07 (d, J = 3.0 Hz, 1H) and
d 7.25 (d, J = 3.3 Hz, 1H) and the occurrence of doublets to meta
* Corresponding author. Tel.: +1 212 543 6518; fax: +1 212 543 6171.
E-mail address: be2168@columbia.edu (B. Easwaramoorthy).
0040-4039/$ - see front matter Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2010.02.173

2498
R. Neelamegam et al. / Tetrahedron Letters 51 (2010) 2497–2499
Table 1
MeO
CHO
OH
Dimerization of phenols and 2-naphthol using an aqueous sodium hypochlorite
Entry Substrate
Time Product25
(h)
Yield
(%)
MeO
CHO
OH
Cl
aq. NaOCl
4% aq. NaOH/H2O
MeO
CHO
OH
3
MeO
CHO
OH
rt, 1h
MeO
CHO
OH
1a
80%
1
1
80
HO
HO
1a
OHC
OMe
OMe
2a
OHC
2a
MeO2C
CHO
Scheme 1.
MeO2C
CHO
OH
OH
HO
OHC
HO
2
4
47
hydrogen–hydrogen can be assigned to the ortho–ortho coupling.
The structures of starting material, product, and reaction condi-
tions are shown in Scheme 1. The product yield was remarkably
high (80%).
1b
CO2Me
2b
CHO
Pending further investigations to the mechanism of dimer for-
mation in aqueous NaOCl, a plausible mechanism for the formation
of the ortho–ortho coupling is depicted in Scheme 2. The mecha-
nism could follow the formation of carbanion intermediate 4 under
basic NaOCl condition followed by electrophilic chlorination to
give intermediate 5. As a final step in mechanism, both the inter-
mediates 4 and 5 might have undergone an oxidative coupling to
form the dimerized product 2a.26 In order to investigate the carb-
anion formation, we performed the reaction of 2,4-dimethylphenol
and 2-chloro-4,6-dimethylphenol in 4% aqueous NaOH solution.
The reaction was monitored for several hours using HPLC.27 This
reaction has not produced a dimer suggesting that the basic condi-
tion alone cannot be the reason for the dimerization and needs the
presence of NaOCl.
In order to explore the generality and scope of the reaction con-
dition, a variety of substrates with electron-donating and electron-
withdrawing substituents were tested. The results are summarized
in Table 1. The reactivity of substrates varied with electron-donat-
ing and electron-withdrawing groups substituted at the 5-position.
In general, the substrates with the electron-donating group gave a
better yield than the substrates with the electron-withdrawing
substituent. This information is insufficient to evolve a mechanism.
All reactions were completed within 1–5 h and gave an exclusively
ortho–ortho coupling product. The final product was isolated by
filtration.
HO
CHO
OH
OH
3
3
HO
OHC
H3C
56
1c
OH
2c
CH3
CH3
OH
OH
4
5
72
H3C
OH
H3C
CH3
CH3
1d
2d
CH3
OH
CH3
CH3
H3C
H3C
OH
OH
5
4
78
H3C
1e
CH3
CH3
2e
We note that by adopting aqueous NaOCl reaction conditions,
dimerization occurs, not only for dimethyl-substituted phenols like
2,4-dimethylphenol but also for trimethyl-substituted phenols like
2,3,5-trimethylphenol (Table 1, products 2d and 2e). The discovery
and development of a more effective and eco-friendly means of
synthesizing compounds is useful and important. Here we have
developed the means to synthesize 1,10-binaphthalene-2,20-diol,
as well as a limited family of other diols, which produces a good
yield in the presence of sodium hypochlorite and aqueous sodium
hydroxide, as an effective alternative to the currently available
methods for synthesizing 1,1-bi-2-naphthol from 2-naphthol.
OH
OH
OH
6
2
58
1f
2f
Compounds 2d–f were characterized according to data reported in Refs. 8,10b,c.
In conclusion, a simple, yet effective aqueous condition has
been created to demonstrate the dimerization of phenol deriva-
tives and naphthol in moderate to high yields.
OMe
OMe
OMe
O
OHC
4% aq. NaOH
+
CHO
2a
1a
Cl
CHO
O
H
NaOCl
CHO
O
O
OMe
5
6
4
Scheme 2.

R. Neelamegam et al. / Tetrahedron Letters 51 (2010) 2497–2499
2499
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.02.173.
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