NaBH4/NaNO3/H2O: A convenient system for selective reduction of aldehydes vs. ketones to their corresponding alcohols

Article abstract of DOI:10.13005/ojc/300452

NaBH₄ (1.25 equivalents) & NaNO₃ (3 equivalents) reduce a variety of aldehydes in the presence of ketones to their corresponding alcohols. Also, regioselectivity and exclusive 1,2-reduction enals to their corresponding allylic alcohols in high to excellent yields was achieved successfully with this reducing system. The reduction reactions were carried out in water as green solvent in high to excellent yields of the products. A nitrate-borane complex [H₃B-NO₃]Na is possibly the active reductant in the reaction mixture.

Full text of DOI:10.13005/ojc/300452

ISSN: 0970-020 X
CODEN: OJCHEG
014, Vol. 30, No. (4):
Pg. 1913-1917
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
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www.orientjchem.org
NaBH /NaNO /H O: A Convenient System for
4
3
2
Selective Reduction of Aldehydes VS. Ketones
to their Corresponding Alcohols
SOHEILAGHADERI and DAVOOD SETAMDIDEH*
Department of Chemistry, Faculty of Sciences, Mahabad Branch,
Islamic Azad University, Mahabad. Iran.
*
Corresponding author E-mail: d.setamdideh@iau-mahabad.ac.ir
http://dx.doi.org/10.13005/ojc/300452
(Received: September 30, 2014; Accepted: November 03, 2014)
ABSTRACT
NaBH (1.25 equivalents) & NaNO (3 equivalents) reduce a variety of aldehydes in the
4
3
presence of ketones to their corresponding alcohols. Also, regioselectivity and exclusive 1,2-
reduction enals to their corresponding allylic alcohols in high to excellent yields was achieved
successfully with this reducing system. The reduction reactions were carried out in water as
green solvent in high to excellent yields of the products. A nitrate-borane complex [H B-NO ]Na is
3
3
possibly the active reductant in the reaction mixture.
Key words: NaBH , Selective Reduction, Aldehydes, NaNO .
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3
INTRODUCTION
alcohols. Herein, we wish to report a convenient
method for the reduction of aldehydes vs. ketones
to their corresponding primary alcohols with NaBH4/
The chemoselective reduction of
aldehydes without affecting ketones is a well-
known strategy in organic synthesis. This subject is
NaNO as reducing system in water.
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1
of great interest and numerous reducing systems
RESULTSAND DISCUSSION
and modified hydroborates have been reported for
2
-4
5-
this subject such as by use of low temperatures
Ketones are less reactive than aldehydes
in reduction reactions. But this character is not
sufficient for selectively reduction of aldehydes vs.
ketones (scheme 1, Path A). To achieve for more
selectivity, the reduction reactions can be done
slower. For this purpose we have examined the
reduction reaction of benzaldehyde as model
6
7
8
9
addition of thiols , metal salts , resins and
polyethylene glycol
borohydrides
reducing properties of NaBH in the presence of
NaNO as the co-reagent for the reduction of
aldehydes vs. ketones to their corresponding
1
0
or by several modified
. We decided to investigate the
1
1-13
4
3

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GHADERI & SETAMDIDEH., Orient. J. Chem., Vol. 30(4), 1913-1917 (2014)
compound with NaBH in aqueous media in the mixture was treated with 1.25 equivalents of NaBH4
4
presence and absence of NaNO as shown in and 3 equivalents of NaNO in 3 mL water at room
3
3
scheme 1. Our observation showed that the temperature. As shown in scheme 1, after 30 min,
reduction reaction of 1 eq. benzaldehyde completed we have observed that the reduction of benzaldehye
at room temperature in the presence of 3 eq. NaNO3 to benzyl alcohols was complete but acetophene
and 1.25 eq. NaBH as shown in table 1.
was intact material i.e. the competition for reduction
4
was favor of benzaldehyde (scheme 1, path B).This
For investigate of selectively reduction result can not achieve by only using NaBH (scheme
4
reaction, a mixture of benzaldehyde (1 eq.) and 1, path A).
acetophenone (1 eq.) was prepared. The reaction
CH OH
2
CH(OH)CH
3
NaBH
4
(1.00 mmol)
O(3mL)
+
RT., 60 min., H
2
CHO
COCH
3
A
B
Conversion: 90%
CH
8%
+
2
OH
CH(OH)CH
3
NaBH
4
(1.25 mmol)/NaNO
3
(3 mmol)
+
RT., 30 min., H O(3mL)
2
Conversion: 100%
0%
Scheme 1:
The efficiency of this protocol was the corresponding alcohols in excellent yields (90-
examined by the reduction of a variety of aldehydes 95%).
in the presence of acetophenone. All reductions
were completed within 30-180 min as shown in table
For more investigate, the reduction of 6-
2
.The molar ratio of NaBH is not different according oxoheptanal and 4-acetylbenzaldehyde as
4
to the nature of the substrates. 1.25 molar ketoaldehydes
to
their
corresponding
equivalents of NaBH and 3 molar equivalents of ketoalcoholes has been done as shown in scheme
4
NaNO per one equivalents of the substrate were 2. The reductions were completed within 50-65 min
3
sufficient to complete conversion of aldehydes to and the corresponding ketoalcoholes have been
isolated in excellent yields (90-92%).
O
O
NaBH
4
3
(1.25 mmol)/NaNO (3 mmol)
O
OH
RT., 50 min., H O(3 mL).,
2
H
H
6-oxoheptanal
92%
H
H
NaBH
4
3
(1.25 mmol)/NaNO (3 mmol)
O
OH
RT., 65 min., H O(3 mL).,
2
O
-acetylbenzaldehyde
O
4
90%
Scheme 2:
The preparation of ally alcohols from the competing 1,2- vs. 1,4-attack by the hydride is often
reduction of conjugated carbonyl compounds is difficult to achieve in organic synthesis. The
conventional in organic synthesis. Regioselective tendency of sodium borohydride to reduce enals in
1,2-reduction of ,-unsaturated aldehydes due to a conjugate sense is highly dependent on solvent

GHADERI & SETAMDIDEH., Orient. J. Chem., Vol. 30(4), 1913-1917 (2014)
1915
1
4
and often ignored. However, several specific
NaNO was thus carried out exclusively in 1,2-
3
15
reagents are available. In this context, we also
investigated the possibility of the 1,2-reduction of
,-unsaturated aldehydes and ketones with
NaBH /NaNO /H O system. The reduction of
cinnamaldehyde by 1.25 molar equivalents of
reduction manner within 40 minutes at room
temperature. In this reaction, cinnamyl alcohol was
obtained in 94% yield as shown in scheme 3 (Table
2, entry 9). Citral also showed the best efficiency
and regioselectivity under this protocol (Table 2,
entry 10).

4
3
2
NaBH in the presence of 3 molar equivalents of
4
Ph
O
Ph
OH
NaBH (1.25 mmol)/NaNO (3 mmol)
4
3
H
RT., 40 min., H O(3 mL).,
2
94%
Scheme 3:
The mechanism for the influence of NaNO3
nitrate-borane specie is generated by the
nucleophilic attack of nitrate ion on borane (scheme
4, II) formed from sodium borohydride and water
(scheme 4, I).The nitrate-borate is less reactive than
is not clear, but as shown in scheme 4 we think that
a possible derivative of nitrate-borane as active
reductant may form in situ under reaction condition.
The possibility to form borane complex via
NaBH and diminishes reactivity.
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1
6-17
nucleophilic attack is also well-known
. The
RCHO
NaOH + H2
H2O
NaNO3
(II)
(
III)
O
N O
O
BH3
(I)
RCH OH
2
Na
NaBH4
BH3
Scheme 4:
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EXPERIMENTAL
quality. IR and H NMR spectra were recorded on
PerkinElmer FT-IR RXI and 300 MHz Bruker
spectrometers, respectively. The products were
General
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All substrates and reagents were
purchased from commercially sources with the best
characterized by their H NMR or IR spectra and
comparison with authentic samples (melting or
Table 1: The optimization reaction condition for the reduction of benzaldehyde
1 mmol) to benzyl alcohol in water (3 mL) at room temperature
(
a
Entry
NaBH (mmol)
NaNO (mmol)
Time (min)
Conversion (%)
4
3
1
2
3
4
5
6
7
1
1
1
0
1
2
3
3
2
3
60
50
40
40
30
50
25
90
95
100
100
100
100
100
1
1.25
1.25
1.5
a
Conversion monitored by TLC and refer to isolated pure product.

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GHADERI & SETAMDIDEH., Orient. J. Chem., Vol. 30(4), 1913-1917 (2014)
boiling points). Organic layers were dried over in water (3 mL) was treated with 6-oxoheptanal
anhydrous sodium sulfate. All yields referred to (0.128 g, 1 mmol) in one portion. The mixture was
isolated pure products. The purity of products was stirred at room temperature for 50 minutes.
1
determinate by H NMR. Also, reactions are Completion of the reaction was monitored by TLC
monitoring over silica gel 60 F254 aluminum sheet.
A typical procedure
(Hexane/EtOAc:9/1).Then, water (5 mL) was added
to the reaction mixture. The mixture was extracted
with ether (3×10 mL) and dried over anhydrous
In a round-bottomed flask (10 mL) Na SO . Evaporation of the solvent afforded the pure
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4
equipped with a magnetic stirrer, a solution of NaBH4 7-hydroxyheptan-2-one (0.236 g, 92%, Table 1,
(
0.047 g, 1.25 mmol) and NaNO (0.255 g, 3 mmol) entry 7).
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Table 2: The Reduction of Aldehydes (1 mmol) vs. Acetophenone (1 mmol)
by NaBH (1.25 eq.)/NaNO (3 mmol) in Water (3 mL) at Room Temperature
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3
a
Entry Aldehydes
Products
Time/min
Yield /%
1
2
3
4
5
6
7
8
9
1
benzaldehyde
benzyl alcohol
30
30
60
30
60
180
50
65
40
60
93
91
90
93
93
95
92
90
94
93
4-bromobenzaldehyde
4-methylbenzaldehyde
4-nitrobenzaldehyde
2-methoxylbenzaldehyde
4-methoxybenzaldehyde
6-oxoheptanal
4-acetylbenzaldehyde
cinnamaldehyde
citral
4-bromobenzyl alcohol
4-methylbenzyl alcohol
4-nitrobenzyl alcohol
2-methylbenzyl alcohol
4-methoxybenzyl alcohol
7-hydroxyheptan-2-one
1-(4-(hydroxymethyl)phenyl)ethanone
cinnamyl alcohol
0
3,7--dimethylocta-2,6-dien-1-ol
a
Yields refer to isolated pure products
CONCLUSION
accomplished with high efficiency of the reductions,
using the appropriate molar ratios of NaBH and
4
In conclusion, we have shown that NaBH4/ NaNO , convenient reaction times (30-180 min) and
3
NaNO /H O reduces a variety of aldehydes vs. easy work-up procedure.Therefore this new protocol
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2
ketones to their corresponding primary alcohols in for chemoselective & regioselective reduction of
high to excellent yields at room temperature. aldehydes could be a useful addition to the present
Reduction reactions were carried out with 1.25 methodologies.
molar equivalents of NaBH in the presence of 3
4
molar equivalents of NaNO in water as green
ACKNOWLEDGMENTS
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solvent. In addition, regioselectivity of this system
was also investigated with exclusive 1,2-reduction
The authors gratefully appreciated the
of conjugated enals to their corresponding allylic financial support of this work by the research council
alcohols in excellent yields. All reductions were of Islamic Azad University branch of Mahabad.
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