A simple biomimetic protocol for the oxidation of alcohols with sodium hypochlorite in the presence of β-cyclodextrin in water

Article abstract of DOI:10.1139/v04-065

A simple and efficient protocol, which is inexpensive, convenient, clean, and facile, for oxidation of alcohols to carbonyl compounds has been developed using sodium hypochlorite in the presence of β-cyclodextrin with water as solvent. A series of alcohols were oxidized at room temperature in excellent yields.

Full text of DOI:10.1139/v04-065

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A simple biomimetic protocol for the oxidation
of alcohols with sodium hypochlorite in the
presence of ␤-cyclodextrin in water
K. Surendra, N. Srilakshmi Krishnaveni, and K. Rama Rao
Abstract: A simple and efficient protocol, which is inexpensive, convenient, clean, and facile, for oxidation of alcohols
to carbonyl compounds has been developed using sodium hypochlorite in the presence of β-cyclodextrin with water as
solvent. A series of alcohols were oxidized at room temperature in excellent yields.
Key words: oxidation, alcohols, sodium hypochlorite, KBr, β-cyclodextrin, biomimetic, water.
Résumé : On a mis au point un protocole simple et efficace d’oxydation des alcools en composés carbonylés qui est
peu coûteux, pratique, propre, et facile et qui fait appel à l’utilisation d’hypochlorite de sodium en présence de β-
cyclodextrine dans l’eau comme solvant. On a oxydé une série d’alcools, à la température ambiante, avec d’excellents
rendements.
Mots clés : oxydation, alcools, hypochlorite de sodium, KBr, β-cyclodextrine, biomimétique, eau.
[
Traduit par la Rédaction] Surendra et al.
Introduction
volved its use in a two-phase system with a phase-transfer
catalyst (18). More recently, two improved methods for
bleach oxidation of alcohols have been developed. One
method employs acetic acid as a solvent in a monophasic
system (19) while the other uses catalytic amounts of
TEMPO in a buffered biphasic medium (20). All these
methods involve the use of biphasic systems employing di-
chloromethane or toluene as the organic phase, a phase-
transfer catalyst, and subsequent formation of overoxidation
products. It is difficult to find a procedure that is selective,
cheap, efficient, and easy to work up.
In a continuation of our work on supramolecular chemis-
try involving cyclodextrins (21), we have attempted the
oxidation of alcohols with sodium hypochlorite in the pres-
ence of β-cyclodextrin in water to develop an environmen-
tally viable process. Cyclodextrins, which are cyclic
oligosaccharides, exert microenvironmental effects leading
to selective reactions. They catalyze reactions by supramo-
lecular catalysis through non-covalent bonding as seen in en-
zymes. Complexation depends on the size, shape, and
hydrophobicity of the guest molecule. Thus, mimicking bio-
chemical selectivity, where orientation of the substrate by
complex formation positioning presents only certain regions
for favorable attack, will be superior to chemical selectivity,
which involves random attack at different regions due to the
intrinsic reactivity of the substrate. These attractive features
of cyclodextrins in the biomimetic modeling of chemical re-
actions prompted us to investigate a variety of oxidations us-
Green chemistry is becoming a central issue in both aca-
demic and industrial research in the 21st century (1). Indus-
trial chemistry is not sustainable without this approach.
Hence, the goal of present-day industrial research is to de-
velop environmentally benign and clean synthetic technolo-
gies, thereby minimizing the cost of waste disposal.
Among various reactions of industrial significance, oxida-
tion of alcohols to carbonyl compounds is a pivotal reaction
and is essential for the preparation of organic intermediates,
fragrances, and food additives (2). Numerous methods have
been developed for these oxidations (3–17). All these tradi-
tional methods involve the use of stoichiometric amounts of
inorganic oxidants, e.g., Cr(VI), which generate copious
amounts of waste heavy metals. Moreover, these methods in-
volve the use of hazardous reagents and solvents, and some-
times expensive reagents and transition metal catalysts,
which interfere and make the recovery of catalyst cumber-
some. In some cases, overoxidation products have also been
detected. The use of molecular O for oxidation is often dif-
2
ficult to control and sometimes results in combustion, and
the reaction is performed with low conversion to avoid over-
oxidation.
Among various oxidizing agents, sodium hypochlorite
seems to be the most inexpensive with the highest potential
for industrial application. The earliest application of NaOCl
as a practical synthetic reagent for alcohol oxidation in-
Received 19 December 2003. Published on the NRC Research Press Web site at http://canjchem@nrc.ca on 2 October 2004.
1
K. Surendra, N.S. Krishnaveni, and K.R. Rao . Organic Chemistry Division-I, Indian Institute of Chemical Technology,
Hyderabad-500 007, India.
1Corresponding author (e-mail: ramaraok@iict.res.in).
Can. J. Chem. 82: 1230–1233 (2004)
doi: 10.1139/V04-065
© 2004 NRC Canada

Surendra et al.
Table 1. Oxidation of alcohols with NaOCl–KBr in the presence of β-CD in water.
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Can. J. Chem. Vol. 82, 2004
ing the substrate β-cyclodextrin complexes with sodium
hypochlorite in water. The complexes were formed with β-
cyclodextrin since it is easily accessible and the least expen-
sive among the cyclodextrins.
Scheme 1.
There are reports of utilizing sodium hypochlorite in con-
junction with cyclodextrins for certain oxidations such as for
the chlorination of anisole at the para position (22), for
asymmetric catalytic epoxidation (23), and sulfoxidation
(
24). To date, no alcohol oxidations to important carbonyl
Table 2. Oxidation of 4-methoxybenzyl alcohol using NaOCl–
KBr system.
compounds have been carried out with sodium hypochlorite
under supramolecular catalysis involving cyclodextrins.
β-CD a
Hypob
(mmol/L) (mmol/L)
KBr
Alcohol
Yield
Experimental
Entry
(mmol/L) (mmol/L) (%)
1
2
3
4
a
0.1
0.1
1.0
1.0
5.0
5.0
5.0
5.0
0.1
1.0
0.1
1.0
1.0
1.0
1.0
1.0
30
45
68
94
Materials
All reactions were carried out in an air atmosphere with-
out any special precautions. Chemicals and solvents were
purchased from Fluka and S. D. Fine Chemicals and used as
1
β-Cyclodextrin.
Sodium hypochlorite.
received. H NMR spectra were obtained on a Gemini-200
b
or 300 MHz spectrometer. IR spectra were recorded on a
Nicolet Nexus 670 FT-IR spectrometer. Mass spectra were
observed on a Micromass VG AutoSpec M spectrometer.
mum yields were obtained when β-cyclodextrin and KBr
were taken in equimolar ratios of 1 equiv. each. However,
the yields were comparatively less with lower ratios of β-
cyclodextrin and KBr. Another point of interest is that the
yields were drastically reduced with lower equivalents of
KBr in spite of higher ratios of β-cyclodextrin. Thus, it
could be seen that KBr plays a major role in these oxidations
and its function can be explained as follows.
The oxidation of alcohols in the presence of β-
cyclodextrin using sodium hypochlorite and KBr can take
place through the initial formation of β-cyclodextrin–
hypochlorite as observed by Breslow and co-workers (22)
followed by the in situ generation of the more active β-
cyclodextrin–hypobromite, which further increases the oxi-
dation yields. This is substantiated by the fact that no oxida-
tion was observed when the alcohol was reacted in the
presence of β-cyclodextrin using hydrogen peroxide and
KBr.
Typical procedure for oxidation
β-Cyclodextrin (1 mmol) was dissolved in water (15 mL)
at 60 °C, then substrate (1 mmol) previously dissolved in
methanol/acetone (1 mL) was added slowly with stirring and
cooled to room temperature. Later, the reaction was cooled
in an ice bath and sodium hypochlorite (5 mmol) was added
slowly, followed by addition of KBr (1 mmol) and subse-
quent stirring at room temperature was continued until the
reaction had gone to completion (Table 1). It was extracted
with ethyl acetate and filtered. The organic layer was dried
over anhydrous Na SO and the solvent was removed in vac-
2
4
uum to obtain the crude product, which was purified by col-
umn chromatography using n-hexane : ethyl acetate (95:5)
on silica gel.
Results and discussion
In conclusion, we have developed an inexpensive, eco-
conscious chemical process for the oxidation of alcohols to
carbonyl compounds in aqueous medium. This methodology
is simple, inexpensive, and can be applied to a variety of
substrates with high potential for industrial applications.
The reaction was carried out by the in situ formation of
the β-cyclodextrin complex of the alcohol in water followed
by addition of sodium hypochlorite and KBr at 0–5 °C and
later stirring at room temperature until the reaction went to
completion. A variety of alcohols have been oxidized to
their corresponding carbonyl compounds in impressive
yields using NaOCl–KBr under supramolecular catalysis in
water (Scheme 1). This methodology is also compatible in
the presence of other functionalities such as methoxy,
methylenedioxy, nitro, hydroxy, and alkene double bonds.
The yields of oxidation products of primary alcohols are
comparatively better than secondary alcohols. Though inclu-
sion complexation takes place in situ during the reaction, the
complexes have been isolated and characterized by powder
X-ray (25) and H NMR studies (26). All the compounds
were characterized by MS, H NMR, and IR techniques fol-
lowed by comparison of the collected data to known com-
pounds (27).
The reaction has also been studied in detail for various ra-
tios of β-cyclodextrin and KBr by taking 4-methoxybenzyl
alcohol as an example (Table 2). It was observed that opti-
Acknowledgement
K. Surendra thanks the Council of Scientific and Indus-
trial Research, New Delhi, India, for the award of a research
fellowship. IICT communication no. 040116.
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