A simple and highly selective biomimetic oxidation of alcohols and epoxides with N-bromosuccinimide in the presence of β-cyclodextrin in water

Article abstract of DOI:10.1002/adsc.200303164

A simple, mild and highly efficient biomimetic oxidation of various alcohols and epoxides with N-bromosuccinimide (NBS) catalyzed by β-cyclodextrin in water has been developed. A series of alcohols and epoxides were oxidized selectively at room temperature in excellent yields. This method is a direct one-pot synthesis under mild conditions using water as solvent and has many advantages over the existing methodologies.

Full text of DOI:10.1002/adsc.200303164

FULL PAPERS
A Simple and Highly Selective Biomimetic Oxidation of
Alcohols and Epoxides with N-Bromosuccinimide in the
≤
Presence of b-Cyclodextrin in Water
N. Srilakshmi Krishnaveni, K. Surendra, K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax: ( ‡ 91)-40-27160757, e-mail: ramaraok@iict.res.in
Received: October 10, 2003; Accepted: January 26, 2004
Abstract: A simple, mild and highly efficient biomi- direct one-pot synthesis under mild conditions using
metic oxidation of various alcohols and epoxides with water as solvent and has many advantages over the
N-bromosuccinimide (NBS) catalyzed by b-cyclodex- existing methodologies.
trin in water has been developed. A series of alcohols
and epoxides were oxidized selectively at room Keywords: alcohols; biomimetic; N-bromosuccini-
temperature in excellent yields. This method is a mide; b-cyclodextrin; epoxides; oxidation; water
Introduction
Green chemistry is becoming a central issue in both
academic and industrial research in the 21 century.
st
[10]
There is an ever-increasing demand to develop sophis- Industrial chemistry is not sustainable without this
ticated target systems involving selective synthetic approach. Thus the development of environmentally
methodologies to discriminate various functional benign and clean synthetic procedures is the goal of
groups. Amongst them, oxidation of alcohols occupies present day researchers. Every reaction should proceed
[
11]
the prime place especially to attain selectivity between with a high atom-economy, thereby minimizing the
,2-diols and controlled oxidation of various alcohols to cost of waste disposal. Thus there is need for developing
1
aldehydes without any overoxidation. Numerous meth- clean oxidation reactions in water without the use of any
ods have been developed which still have some limi- harmful organic solvents because water is a safe,
tations. Amongst them, stoichiometric oxidants such as economical and environmentally benign solvent.[ In
manganese dioxide, hypervalent iodine, activated our efforts to develop biomimetic approaches for
dimethyl sulfoxides, chromium(VI)-based oxidants,
12]
[
1]
[2]
[
3]
[4]
[13]
chemical reactions involving cyclodextrins in water,
etc. were the most commonly used. Although these we report herein for the first time the highly selective
methods are being used in various types of organic oxidation of a variety of alcohols, diols and epoxides as
syntheses, the heavy metal oxidants, apart from being their b-cyclodextrin complexes with N-bromosuccini-
expensive, form toxic wastes, whereas activated dimeth- mide in water without the presence of any acidic or basic
yl sulfoxide gives rise to awfully smelling dimethyl catalyst (Schemes 1 and 2).
sulfide. Regarding hypervalent iodine, oxidants such as
Cyclodextrins are cyclic oligosaccharides possessing
IBX are either explosive on impact or on heating to hydrophobic cavities, which bind substrates selectively
more than 2008C. Another most conventional industrial and catalyze chemical reactions with high selectivity.
oxidant,[ nitric acid, though cheap unavoidably forms They catalyze reactions by supramolecular catalysis
various nitrogen oxides. However, even catalytic oxida- involving reversible formation of host-guest complexes
tions have some limitations such as pH of the medium, by non-covalent bonding as seen in enzymes. Complex-
controlled temperature, hazardous reagents and sol- ation depends on the size, shape and hydrophobicity of
5]
[
6,7]
vents, formation of side products etc. The N-bromo-
succinimide (NBS) oxidations of alcohols reported are
usually carried out using either anhydrous solvents or in
acidic or basic media at varied temperatures. The
selectivities observed were also not encouraging in
[8]
some cases. Oxidation of various alcohols still remains
the most problematic process. Thus there is still demand
for clean and safe oxidation procedures.
Scheme 1.
346
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/adsc.200303164
Adv. Synth. Catal. 2004, 346, 346 ± 350

Biomimetic Oxidation of Alcohols and Epoxides with NBS
FULL PAPERS
(
Entry 21) also the product obtained in dichlorome-
thane (in the absence of b-CD) was only the aldehyde by
the oxidation of the primary alcohol retaining the
[
7]
oxirane as observed by Mukaiyama et al., whereas in
the presence of b-CD in water the a-hydroxyketone was
obtained as the product. When a catalytic amount of
cyclodextrin (0.1 mmol per 1 mmol of substrate) was
used the reaction with alcohols did not go to completion
and the product formation was only to the extent of 40 ±
Scheme 2.
the guest molecule. Thus, mimicking biochemical selec- 50% under the reported reaction conditions. In the case
tivity, which is due to orientation of the substrate by of epoxycinnamyl alcohol only the primary alcohol was
complex formation positioning only a certain region for oxidized giving epoxycinnamyl aldehyde.
favorable attack, will be superior to chemical selectivity,
The mechanism of oxidation has been postulated as
which involves random attack due to intrinsic reactivity follows. The fact that these reactions do not take place in
of the substrate at different regions. These attractive the absence of cyclodextrin in water and that the starting
features of cyclodextrins in the biomimetic modeling of substrate was intact indicates the essential role of
chemical reactions prompted us to investigate a variety cyclodextrin. Here the role of cyclodextrin appears to
of oxidations using the substrate-b-cyclodextrin com- be to form an inclusion complex of alcohol/epoxidefrom
plexes with NBS in water. The complexes were formed the secondary side with the attack of NBS from the
with b-cyclodextrin since it is easily accessible and least primary side of CD enabling the reaction to proceed
expensive among the cyclodextrins.
(Figure 1). The evidence for this mechanistic approach
was deduced from H NMR spectroscopy. These studies
1
were carried out with 4-methoxybenzyl alcohol as a
Results and Discussion
In general, the reaction was carried out by the in situ
formation of the b-cyclodextrin complex of the substrate
in water followed by the addition of NBS and stirring at
room temperature to give the corresponding carbonyl
compounds in impressive yields (Table 1). The reaction
goes smoothly at room temperature without the for-
mation of any side products or rearrangements. No
overoxidation to acids was observed in the case of
aldehyde products (Entries 1 ± 8, Table 1). This method-
ology is also compatible to the presence of other
functionalities such as methoxy, nitro, and amino,
hydroxy, methylenedioxy and alkene double bonds.
These reactions are highly selective for vicinal diols in
oxidizing only the secondary hydroxy group a to the
benzene ring (Entries 18 ± 20, Table 1). In the case of
various types of epoxides (Entries 21 ± 24, Table 1), a-
hydroxyketones were the only products obtained in
excellent yields keeping intact the functionalities such as
primary OH, TBDMS, OMe and OEt. These cyclo-
dextrin-mediated, water-based reactions proceed under
mild conditions and are also useful from the point of
view of not having to handle flammable and anhydrous
organic solvents and toxic reagents. Although inclusion
complexation takes place in situ during the reaction, the
complexes have been isolated and characterized by
powder X-ray[ and H NMR studies. All the com-
14]
1
[15]
1
pounds were characterized by mass, H NMR, IR and by
[
16]
comparison with known compounds. In these reac-
tions succinimide was obtained as the by-product. This
has been recycled to NBS as described in the exper-
imental section. Cyclodextrin has also been recovered
and reused. In the case of epoxycinnamyl alcohol
Adv. Synth. Catal. 2004, 346, 346 ± 350
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¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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FULL PAPERS
N. Srilakshmi Krishnaveni et al.
Figure 1.
1
representative example. A comparison of the H NMR
spectra (D O) of b-cyclodextrin, b-cyclodextrin-alcohol
2
and freeze-dried reaction mixtures at 5 h and 8 h was
undertaken. It can be seen from Figure 2 that there is a
clear upfield shift of the H3 (0.03) and H5 protons (0.04)
in the b-CD-alcohol complex (Figure 2B) The shift of
these protons of cyclodextrin in the cyclodextrin-alcohol
complex (Figure 2B) as compared to cyclodextrin
(
Figure 2A) indicates the formation of inclusion com-
1
[15]
Figure 2. H NMR spectra: A: b-CD; B: b-CD-alcohol com-
plex. However, it can be observed from the spectra of
the reaction mixtures at 5 h and 8 h (Figures 2C and 2D)
that in these complexes, apart from retention of the
plex; C: 5-h reaction mixture; D: 8-h reaction mixture.
348
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Adv. Synth. Catal. 2004, 346, 346 ± 350

Biomimetic Oxidation of Alcohols and Epoxides with NBS
FULL PAPERS
upfield character of H3 and H5 protons, there is also an Acknowledgements
upfield shift of the H6 proton (i.e., 0.02 ppm at 5 h
K. S. thanks CSIR, New Delhi, India, for the award of a research
fellowship.
0
.025 ppm at 8 h, respectively). This indicates the
complexation of NBS from the primary side of CD.
1
From these H NMR studies it could be seen that while
the alcohol is still being retained in the cavity, NBS
complexes from the primary side (Figure 1) for the
reaction to proceed further. Thus, it can be seen that the
reaction takes place through supramolecular catalysis.
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b-Cyclodextrin (1 mmol) was dissolved in water (15 mL) at
608C, the substrate (1 mmol) dissolved in methanol/acetone
(
1 mL) was added slowly with stirring and cooled to room
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