Water as a green solvent for fast and efficient reduction of carbonyl compounds with NaBH4 under microwave irradiation

Article abstract of DOI:10.1002/jccs.200500169

Reduction of varieties of carbonyl compounds such as aldehydes, ketones, α,β-unsaturated aldehydes and ketones, α-diketones and acyloins was carried out very fast and efficiently by sodium borohydride in water under microwave irradiation. The corresponding product alcohols were obtained in high to excellent yields.

Full text of DOI:10.1002/jccs.200500169

Journal of the Chinese Chemical Society, 2005, 52, 1179-1184
1179
Water as a Green Solvent for Fast and Efficient Reduction of Carbonyl
Compounds with NaBH4 under Microwave Irradiation
Behzad Zeynizadeh* and Davood Setamdideh
Department of Chemistry, Faculty of Sciences, Urmia University, Urmia 57159-165, Iran
Reduction of varieties of carbonyl compounds such as aldehydes, ketones, a,b-unsaturated aldehydes
and ketones, a-diketones and acyloins was carried out very fast and efficiently by sodium borohydride in wa-
ter under microwave irradiation. The corresponding product alcohols were obtained in high to excellent
yields.
Keywords: NaBH4; Microwave; Carbonyl compounds; Green solvent; Water.
INTRODUCTION
actions using domestic microwave ovens.
Reduction by hydrides, which at one time seemed im-
possible to carry out in water, are now a reality. Our literature
review shows that though the application of NaBH4 in water
or aqueous media has been reported for some reduction pur-
poses,6 the reduction of carbonyl compounds in water, as far
as we know, has not been reported. The lack of information
for systematic reduction of carbonyl compounds in water and
our ongoing attentions to the development of modified hy-
droborate agents in organic synthesis7 encouraged us to in-
vestigate this transformation with NaBH4 under microwave
irradiation in water as a green and good solvent for transfer-
ring electromagnetic energy into heat and so driving a reduc-
tion reaction effectively. Herein, we describe a fast and effi-
cient method for the reduction of varieties of carbonyl com-
pounds such as aldehydes, ketones, conjugated aldehydes
and ketones, a-diketones and acyloins to their corresponding
alcohols with NaBH4 under microwave irradiation (Scheme
I).
It has been over forty years since sodium borohydride
became widely recognized as the reagent of choice for the re-
duction of carbonyl compounds in protic solvents.1 In the
past decades, the utility of sodium borohydride has been
greatly expanded, and different techniques and modifications
have been developed for this mild reducing agent to effect
reduction of organofunctional groups in a broad spectrum
of solvents.1,2a In this context, we extensively reviewed the
preparations and applications of modified hydroborate
agents in organic synthesis.2 The use of a large amount of
conventional volatile solvents required to conduct a chemical
reaction creates ecological and economic concerns. Conse-
quently deletion or replacement of volatile organic solvents
from reaction medium has been a major emphasis of green
chemistry.3 In this line, the use of water as a green solvent can
be the best medium of choice to perform chemical reactions.
In the last decade, a large number of publications have dem-
onstrated the value of performing chemical reactions in water
or aqueous media.4
Scheme I
On the other hand, microwave irradiation as an uncon-
ventional energy source has been widely used to perform
many kinds of chemical reactions, and numerous reviews and
papers have demonstrated its importance.5 It is now clear that
the microwave dielectric heating effect uses the ability of liq-
uids and solids to transform electromagnetic energy into heat
and so drive chemical reactions effectively and quickly.5c-e
This in situ mode of energy conversion has attracted much at-
tentions of chemists and has resulted in the development of
many techniques to carry out microwave-assisted organic re-
R
R
NaBH4/H2O
Microwave, 15 sec-5 min
70-99%
O
OH
R'
R'
RESULTS AND DISCUSSION
We first optimized reaction conditions with the reduc-
tion of benzaldehyde as a model compound by NaBH4 in wa-
ter under microwave irradiation. The results showed that us-
* Corresponding author. E-mail: b.zeynizadeh@mail.urmia.ac.ir

1180 J. Chin. Chem. Soc., Vol. 52, No. 6, 2005
Zeynizadeh and Setamdideh
ing a 0.5 molar equivalent of NaBH4 per molar equivalent of
the aldehyde in 2 mL water and 30% power amplitude of mi-
crowave oven (300 W) was the best for reduction reaction.
The reaction was completed in 30 sec and benzyl alcohol was
obtained in 96% yield. To show the further utility of this pro-
tocol, we applied the optimal conditions for the reduction of
structurally different aliphatic and aromatic aldehydes with
sodium borohydride. The use of 0.5-1 molar equivalents of
sodium borohydride was sufficient for the complete reduc-
tion of aldehydes and the corresponding primary alcohols
were obtained in 82-98% yields within 30-60 sec. The results
of these reductions are summarized in Table 1.
eral specific reagents and some of them are now commer-
cially available.9
In this context, we also investigated the possibility of
1,2-reduction of a,b-unsaturated aldehydes and ketones with
NaBH4 in water under microwave irradiation. The irradiation
of cinnamaldehyde by microwave (700 W) in the presence of
one molar equivalent of NaBH4 in water (2 mL) was carried
out exclusively in 1,2-reduction manner within 50 sec. In this
reaction, cinnamyl alcohol was obtained in 98% yield. This
achievement prompted us to evaluate the behavior of other
enals and enones in respect to this transformation. Citral also
showed the best efficiency and regioselectivity under micro-
wave irradiation. Reduction of conjugated ketones such as
benzalacetone and b-ionone were achieved quickly and effi-
ciently with 2 molar equivalents of NaBH4 in water under mi-
crowave irradiation (700 W). The irradiation of benzalaceto-
phenone in 5 min gave only 70% yield; however, the 1,2-re-
duction product was obtained from the reaction mixture (Ta-
ble 4).
In the next attempt, we turned our attention to the re-
duction of ketones under the defined conditions. Reduction
of ketones, because of their less reactivity relative to alde-
hydes, needs the use of 1.5-2 molar equivalents of NaBH4 un-
der microwave irradiation (700 W). Different kinds of aro-
matic and aliphatic ketones were subjected to NaBH4 in water
(2 mL) under microwave irradiation. The results also showed
that the corresponding secondary alcohols were obtained in
excellent yields within 15-60 sec. In the case of benzophe-
none, probably because of its bulk hindrance, a reduction re-
action required 4 molar equivalents of NaBH4, and benz-
hydrol was obtained in 90% yield after 5 min irradiation (Ta-
ble 2). The work-up procedure was easy: addition of distilled
water to the reaction mixture and then extracting with diethyl
ether afforded the crude corresponding alcohol for further pu-
rification with short column chromatography on silica gel.
The utility of this protocol was further examined with
the reduction of a-diketones and acyloins. Their reductions
were carried out with 2 molar equivalents of NaBH4 in water
(2 mL) under microwave irradiation (700 W). The reactions
were completed within 1-3 min and the corresponding vicinal
diols were obtained in 91-99% yields (Table 3). All attempts
to reduce a-diketones to acyloin compounds were unsatisfac-
tory and only vicinal diols were obtained from the reactions.
Ally alcohols are important synthetic materials and
their preparations from the reduction of conjugated carbonyl
compounds are one of the easiest in organic synthesis.1 Re-
gioselective 1,2-reduction of a,b-unsaturated aldehydes and
ketones with metal hydride reducing agents due to competing
1,2- vs. 1,4-attack by the hydride is often difficult to achieve
in organic synthesis. In spite of the substantial evidence, the
tendency for sodium borohydride to reduce enones or enals in
a conjugate sense is highly solvent-dependent and often ig-
nored;8 however, the requirement for reduction to corre-
sponding allylic alcohols has led to the development of sev-
CONCLUSION
In conclusion, we have shown that water as a green sol-
vent can effectively replace of the conventional volatile sol-
vents in the reduction of a variety of carbonyl compounds
with sodium borohydride under microwave irradiation. The
reductions were completed within 15 sec-5 min with high to
excellent yields of the corresponding alcohols. Reduction of
a-diketones and acyloin compounds produced the corre-
sponding vicinal diols in excellent yields. Conjugated car-
bonyl compounds under the defined conditions showed an
excellent efficiency in an exclusive 1,2-reduction manner.
Therefore, we think that this protocol with the above advan-
tages as well as the easy work-up procedure could be a useful
addition to the present methodologies.
EXPERIMENTAL SECTION
All microwave assisted reactions were carried out in a
Yusch household microwave oven (1000 W). The instrument
was modified for laboratory applications with an external re-
flux condenser. All substrates and reagents were obtained
from commercial sources of the highest quality and were
used without further purification. The products were charac-
terized by a comparison with authentic samples (melting or

Reduction in Water under Microwave Irradiation
J. Chin. Chem. Soc., Vol. 52, No. 6, 2005 1181

1182 J. Chin. Chem. Soc., Vol. 52, No. 6, 2005
Zeynizadeh and Setamdideh
boiling points) and their 1H NMR or IR spectra. Organic lay-
ers were dried with anhydrous sodium sulfate before concen-
tration in vacuo. All yields refer to isolated products. TLC
was applied for the purity determination of substrates, prod-
ucts and reaction monitoring over silica gel 60 F254 aluminum
sheets. Products were purified by column chromatography

Reduction in Water under Microwave Irradiation
J. Chin. Chem. Soc., Vol. 52, No. 6, 2005 1183
packed with silica gel 60 (70-230 mesh ASTM).
dehyde (0.106 g, 1 mmol) was then added dropwise to the re-
sulting solution. After fitting the flask to the external con-
denser at the inside of the oven, the mixture was irradiated
with a microwave oven (30% power amplitude » 300 W) for
30 sec. The progress of the reaction was monitored by TLC
(eluent; CCl4/Et2O: 5/2). At the end of the reduction, distilled
water (5 mL) was added to the reaction mixture and it was
A Typical Procedure for Microwave-Assisted Reduction
of Carbonyl Compounds with NaBH4 in Water
In a round-bottomed flask (10 mL) charged with dis-
tilled water (2 mL), NaBH4 (0.019 g, 0.5 mmol) was added
and swirling the flask makes a clear solution. Neat benzal-

1184 J. Chin. Chem. Soc., Vol. 52, No. 6, 2005
Zeynizadeh and Setamdideh
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ACKNOWLEDGMENT
The authors gratefully appreciate the financial support
of this work by the Research Council of Urmia University.
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Received March 14, 2005.
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