NaBH4/NaHSO4·H2O a heterogeneous acidic system for a mild and convenient reduction of carbonyl compounds under protic condition

Article abstract of DOI:10.1515/znb-2005-0417

NaBH₄ in the presence of sodium bisulfate (NaHSO ₄·H₂O), a weakly acidic reagent, efficiently reduces a variety of carbonyl compounds such as aldehydes, ketones, α, β-unsaturated aldehydes and ketones, α-diketones and acyloins to their corresponding alcohols in acetonitrile under heterogeneous condition. Reduction reactions were accomplished at room temperature or under reflux condition.

Full text of DOI:10.1515/znb-2005-0417

NaBH4/NaHSO4·H2O a Heterogeneous Acidic System for a Mild and
Convenient Reduction of Carbonyl Compounds under Protic Condition
Behzad Zeynizadeh and Tarifeh Behyar
Department of Chemistry, Faculty of Sciences, Urmia University, Urmia 57159-165, Iran
Reprint requests to Prof. B. Zeynizadeh. E-mail: b.zeynizadeh@mail.urmia.ac.ir
Z. Naturforsch. 60b, 453 – 457 (2005); received October 21, 2004
NaBH4 in the presence of sodium bisulfate (NaHSO4·H2O), a weakly acidic reagent, efficiently
reduces a variety of carbonyl compounds such as aldehydes, ketones, α,β-unsaturated aldehydes and
ketones, α-diketones and acyloins to their corresponding alcohols in acetonitrile under heterogeneous
condition. Reduction reactions were accomplished at room temperature or under reflux condition.
Key words: Borohydride Reduction, Sodium Bisulfate, Carbonyl Compounds
Introduction
So, this subject and our continuous efforts for the in-
troduction of modified hydroborate agents in organic
synthesis [5b– g, 10] encouraged us to investigate this
kind of combination system. Herein, we report for the
first that time sodium borohydride in the presence of
sodium bisulfate, a weakly acidic reagent, can reduce
efficiently a variety of carbonyl compounds such as
aldehydes, ketones, conjugated carbonyl compounds,
α-diketones and acyloins to their corresponding alco-
hols in acetonitrile under heterogeneous condition at
room temperature or reflux.
During the past decades, sodium borohydride as a
key reagent has played an important role in the re-
duction of organofunctional groups in modern organic
synthesis [1]. This reagent is a relatively mild reduc-
ing agent and mostly used for the reduction of alde-
hydes and ketones in protic solvents. In order to con-
trol the reducing power of NaBH4, hundreds of substi-
tuted boron hydrides have been made and introduced
in chemical literature and many of them are now com-
mercially available. In fact, advances in this field have
been realized by: a) substitution of the hydride(s) with
other substituents which may exert marked steric or
electronic influences upon the reactivity of substituted
complex ion [2], b) variation of metal cation in the hy-
dride complex [3], c) a concurrent cation and hydride
exchange [4], d) use of amino or phosphino ligands to
alter behavior of the metal hydroborates [5], e) combi-
nation of tetrahydroborates with Lewis acids, additives
and mixed solvent systems [6], f) changing the cation
to quaternary ammonium and phosphonium tetrahy-
droborates [7], g) use of polymers or solid supports for
supporting the hydride species [8]. In this context, we
have extensively reviewed the preparations and appli-
cations of modified hydroborate agents in organic syn-
thesis [5c, d, 9].
Results and Discussion
Preliminary experiments showed that reduction of
benzaldehyde as a model compound took place with
one molar equivalent of NaBH4 in acetonitrile (the
optimal aprotic solvent) within 90 minutes at room
temperature. By adding 0.3 molar equivalents of
NaHSO4·H2O to the mentioned reaction, the reduc-
tion reaction was accelerated dramatically and com-
pleted within 10 minutes (Scheme 1). It is notable that
due to the low solubility of sodium bisulfate in ace-
tonitrile, the reaction takes place under heterogeneous
conditions. This acceleration prompted us to investi-
gate the influence of this weakly acidic reagent and the
optimum reaction conditions for the reduction of alde-
In the line of outlined strategies and our literature
review about the different kinds of combination sys-
tems of NaBH4 with additives for the reduction of
functional groups [6, 9], we realized that for the use
of this reducing agent in the presence of an acidic cat-
alyst or reagent, as far as we know, there is no report.
Scheme 1.
c
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454
B. Zeynizadeh – T. Behyar · Reduction of Carbonyl Compounds with NaBH4/NaHSO4·H2O System
Table 1. Reduction of alde-
hydes to their alcohols with
NaBH4/NaHSO4·H2Oa.
Entry
Substrate
Product
Molar ratio
Time Yield
Subs./NaBH4/NaHSO4 [min] [%]b
1
2
3
1:1:0.3
10
7
94
99
96
a
All reactions were carried out in
1:0.7:0.3
1:0.5:0.3
CH3CN (3 ml) at room tempera-
b
ture; yields refer to isolated pure
products.
3
4
1:0.5:0.3
1
95
5
6
7
1:1:0.3
1:1:0.3
1:1:0.3
20
15
6
97
97
94
8
1:2:0.4
6
95
9
10
11
1:1:0.3
10
2
99
93
92
1:0.5:0.2
1:0.5:0.2
5
12
13
1:0.7:0.3
1:0.7:0.3
2
2
98
95
14
1:1:0.4
25
97
15
16
1:0.7:0.3
1:0.5:0.2
5
1
97
94
17
1:1:0.3
18
93
hydes. The results showed that generally the use of
The corresponding primary alcohols were obtained
0.5– 1 and 0.2 – 0.4 molar equivalents of NaBH4 and in high to excellent yields, and the results of these re-
NaHSO4·H2O, respectively, was sufficient for the re- ductions are summarized in Table 1. In the next at-
duction of different aliphatic and aromatic aldehydes tempt, we turned our attention to the reduction of ke-
in acetonitrile at room temperature.
tones with this reducing system. Because of the inher-
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B. Zeynizadeh – T. Behyar · Reduction of Carbonyl Compounds with NaBH4/NaHSO4·H2O System
455
Table 2. Reduction of ke-
tones to their alcohols with
NaBH4/NaHSO4·H2Oa.
Entry
Substrate
Product
Molar ratio
Time Yield
Subs./NaBH4/NaHSO4 [min] [%]b
1
1:2:0.5
7
99
a
All reactions were carried out in
CH3CN (3 ml) under the defined
condition; b yields refer to isolated
pure products.
2
3
4
5
6
1:2:0.7
1:2:0.7
1:2:0.7
1:2:0.3
1:2:0.5
45
27
20
15
20
95
98
96
96
97
7
8
1:2:0.5
1:2:0.5
18
20
94
97
9
1:2:0.5
25
96
10
11
12
13
1:2:0.3
1:2:0.2
1:2:0.3
1:2:0.3
5
6
6
5
92
94
95
91
ently lower reactivity of ketones relative to aldehydes, for 12 hours without using NaHSO4·H2O. The results
these reductions took place under forcing conditions. showed that in this case we had only 8 – 10% conver-
Reduction of different aliphatic and aromatic ketones sion. When the reaction was performed in the presence
by using 2 and 0.3 – 0.7 molar equivalents of sodium of 0.5 molar equivalents of NaHSO4·H2O, it was com-
borohydride and sodium bisulfate, respectively, were pleted in 7 minutes and the corresponding benzhydrol
carried out in acetonitrile under reflux. The reductions was obtained in 99% yield (Scheme 2).
were completed within 5 – 45 minutes and the corre-
sponding secondary alcohols were obtained in high to
excellent yields (91 – 99%). The results of these reduc-
tions are summarized in Table 2.
To clarify the effect and influence of sodium bisul-
fate in the reduction of ketones, we performed the re-
duction of benzophenone as a model compound with
2 molar equivalents of NaBH4 under reflux condition
The reduction of α-diketones and acyloin com-
pounds with NaBH4/NaHSO4·H2O system was also
examined. Reduction of α-diketones with 2:0.5 molar
equivalents of NaBH4/NaHSO4·H2O to give the cor-
responding vicinal diols was carried out efficiently in
acetonitrile under reflux condition. The reactions were
completed within 6 – 8 minutes (Table 3). All attempts
to reduce α-diketones to acyloin compounds were un-
satisfactory and only vicinal diols were obtained from
the reactions. Reduction of acyloin compounds was
also achieved easily and efficiently with this reducing
system under the defined conditions (Table 3).
Allyl alcohols are important synthetic materials and
their preparation from the regioselective 1,2-reduction
Scheme 2.
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456
B. Zeynizadeh – T. Behyar · Reduction of Carbonyl Compounds with NaBH4/NaHSO4·H2O System
Table 3. Reduction of α-
diketones and acyloins with
NaBH4/NaHSO4·H2Oa.
Entry
Substrate
Product
Molar ratio
Time Yield
Subs./NaBH4/NaHSO4 [min] [%]b
1
2
3
4
5
6
7
1:2:0.5
1:2:0.5
1:2:0.5
1:2:0.5
1:2:0.5
1:2:0.5
1:2:0.5
6
4
8
5
7
4
7
97
98
98
99
93
96
95
a
All reactions were carried out in
CH3CN (3 ml) under reflux condi-
b
tion; yields refer to isolated pure
products.
Table 4. Reduction
of conjugated car-
bonyl compounds
with NaBH4/NaH
SO4·H2Oa.
Entry
Substrate
Product
Molar ratio
Subs./NaBH4/NaHSO4
Condition Ratio Time Yield
1,2:1,4 [min] [%]b
1
2
3
4
1:1:0.3
1:2:0.5
1:2:0.7
1:1:0.3
RT
100:0
2
97
97
98
92
Reflux 100:0
6
a
All
reactions
out
were carried
Reflux 100:0 13
RT 100:0 25
in CH3CN (3 ml)
under the defined
b
condition;
yields
refer to isolated pure
products.
5
1:2:0.7
Reflux 100:0 12
98
of α,β-unsaturated aldehydes and ketones is a widely
The mechanism for the influence of NaHSO4 is not
utilized method in organic synthesis. Considerable ef- clear, but we think that the following pathways may
forts have been made in the development of vari- play a key role in these accelerations: a) sodium bisul-
ous hydride transferring agents for this purpose [1]. fate heterogeneously protonates the carbonyl group
In this context, we decided to evaluate the ability of which make it more susceptible for the hydride at-
the combination system of NaBH4 and NaHSO4·H2O tack, b) this weakly acidic reagent heterogeneously
for the regioselective 1,2-reduction of conjugated car- catalyzes the decomposition of the borohydride moi-
bonyl compounds. We observed that reduction of cin- ety with the liberation of active molecular hydrogen
namaldehyde as a model compound occurred exclu- which reduces the carbonyl group, since in all reac-
sively as a 1,2-reduction with 1:0.3 molar equivalents tions we observed the gentle generation of hydrogen
of NaBH4/NaHSO4·H2O in acetonitrile at room tem- gas throughout the reduction.
perature. The reduction was completed within 2 min-
utes with an excellent yield of cinnamyl alcohol (97%).
Reduction of citral was also achieved with this reduc-
In conclusion, we have shown that reduction of a
variety of carbonyl compounds with NaBH4 was ac-
celerated dramatically in the presence of weakly acidic
ing system and geraniol was obtained in high yields. NaHSO4·H2O in acetonitrile. The reactions were ac-
The reduction of conjugated ketones such as benza- complished under heterogeneous conditions. Reduc-
lacetone, benzalacetophenone and β-ionone were also
tion of aldehydes was performed at room temperature
carried out effectively with 2:0.5 molar equivalents of and that of ketones under reflux condition. The re-
NaBH4/NaHSO4·H2O under reflux condition. The cor- gioselective reduction of α,β-unsaturated aldehydes
responding secondary allylic alcohols were obtained in
excellent yields and regioselectivity (Table 4).
and ketones was achieved in exclusive 1,2-reduction
manner. The ability of this reducing system was fur-
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B. Zeynizadeh – T. Behyar · Reduction of Carbonyl Compounds with NaBH4/NaHSO4·H2O System
457
ther investigated with the reduction of α-diketones and Reduction of carbonyl compounds to their alcohols with the
NaBH4/NaHSO4·H2O system; typical procedure
acyloin compounds to their corresponding vicinal di-
ols. Therefore we think that these advantages as well
as high to excellent efficiency of the reductions could
make this procedure a synthetically useful addition to
the present methodologies.
To a round-bottomed flask (10 ml) equipped with mag-
netic stirrer and charged with the solution of benzaldehyde
(0.106 g, 1 mmol) in CH3CN (3 ml), NaHSO4·H2O (0.041 g,
0.3 mmol) and then NaBH4 (0.038 g, 1 mmol) was added.
The resulting mixture was stirred magnetically at room tem-
perature for 10 min. TLC monitored the progress of reac-
tion (eluent CCl4/Et2O (5:2)). After completion of the reac-
tion, distilled water (3 ml) was added to the reaction mixture
which was stirred for an additional 5 min. The mixture was
extracted with CH2Cl2 (3×8 ml) and dried over anhydrous
sodium sulfate. Evaporation of the solvent and short column
chromatography of the resulting crude material over silica
gel (eluent CCl4/Et2O (5:2)) afforded the pure liquid benzyl
alcohol (0.l02 g, 94% yield, Table 1).
Experimental Section
General
All substrates and reagents were obtained from commer-
cially sources with highest quality and used without further
purification. The products were characterized by a compar-
ison with authentic samples (melting or boiling points) and
their 1H NMR or IR spectra. Organic layers were dried with
anhydrous sodium sulfate before concentration in vacuo. All
yields refer to isolated pure products. TLC was applied for
the purity determination of substrates or products and reac-
tion monitoring on silica gel PolyGram SILG/UV-254 plates.
Acknowledgements
The authors gratefully acknowledge the financial support
of this work by the research council of Urmia University.
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