Ultrasonic-promoted selective reduction of aldehydes vs. ketones by NaBH4/PhCO2Na/H2O

Article abstract of DOI:10.13005/ojc/320329

In this study, we have investigated the selective reduction of aldehydes vs. ketones by NaBH₄/PhCO₂Na/H₂O system under ultrasound irradiation. NaBH₄ (1.25 equivalents) and PhCO₂Na (2 equivalents) is optimized conditions for reduce a variety of aldehydes (1 mmol) in the presence of ketones (1 mmol) to their corresponding alcohols in water as green solvent in high to excellent yields of the product (90-95%). A benzoate-borane complex [PhCO₂-H₃B]Na is possibly the active reductant in the reaction mixture.

Full text of DOI:10.13005/ojc/320329

ISSN: 0970-020 X
CODEN: OJCHEG
016, Vol. 32, No. (3):
Pg. 1539-1543
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
Ultrasonic-Promoted Selective Reduction of
Aldehydes vs. ketones by NaBH /PhCO Na/H O
4
2
2
MINA MIRTAgHIzAꢀEH and ꢀAꢁOOꢀ SETAMꢀIꢀEH*
Department of Chemistry, Faculty of Sciences, Mahabad Branch,
Islamic Azad University, Mahabad. Iran.
*
Corresponding author E-mail: davood.setamdideh@gmail.com
http://dx.doi.org/10.13005/ojc/320329
(Received: February 09, 2016; Accepted: March 29, 2016)
ABSTRACT
In this study, we have investigated the selective reduction of aldehydes vs. ketones by
NaBH /PhCO Na/H O system under ultrasound irradiation.NaBH (1.25 equivalents) and PhCO Na
4
2
2
4
2
(
2 equivalents) is optimized conditions for reduce a variety of aldehydes (1 mmol) in the presence
of ketones (1 mmol) to their corresponding alcohols in water as green solvent in high to excellent
yields of the product (90-95%). A benzoate-borane complex [PhCO -H B]Na is possibly the active
2
3
reductant in the reaction mixture.
Keywords: NaBH , Selective Reduction, Aldehydes, PhCO Na, Ultrasound.
4
2
INTROꢀUCTION
borohydride (NaBH ) in the presence of sodium
4
benzoate (PhCO Na) as co-reagent for the reduction
2
Ultrasound irradiation is an exciting new
unconventional energy in organic synthesis during
the past decade. The promoted organic reaction
by ultrasound irradiation has higher yield, shorter
of aldehydes vs. ketones to their corresponding
alcohols in water. This reducing system has been
promoted by ultrasound irradiation.
1
reaction time and milder conditions .
RESULTS ANꢀ ꢀISCUSSION
The Reduction of aldehydes vs. ketones
Aldehydes are more reactive than ketones
in reduction reactions. But to achieve for more
selectivity, the reduction reactions can be done
slower. We have examined the reduction reaction
of benzaldehyde as model compound with NaBH4
in aqueous media in the presence and absence
2
is interesting in organic synthesis . For this
2-3
achievement several modified borohydrides have
been reported. Also some reducing systems have
been used for this purpose such as: use of low
4
-5
6
7
temperatures addition of thiols , metal salts ,
8
9
resins and polyethylene glycol . In this context we
have investigated the reducing properties of sodium
of PhCO Na. Our experiments showed that the
2
reduction reaction of 1 eq.benzaldehyde completed

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MIRTAGHIꢀADEH & SETAMDIDEH, Orient. J. Chem., Vol. 32(3), 1539-1543 (2016)
at room temperature in the presence of 2 eq. a,b-unsaturated alcohol were obtained in 90% yield
PhCO Na and 1.25 eq. NaBH in H O (3 mL) under as shown in scheme 3. Cinnamaldehyde and Citral
2
4
2
ultrasonic irradiation (table 1,entry 10) as shown in have showed the best efficiency and regioselectivity
scheme 1. under this protocol.
After this achievement, we have decided
The mechanism for the influence of
to investigate of chemoselective reduction of PhCO Nais not clear, but as shown in scheme 4, we
2
aldehydes vs. ketones under optimized reaction think that a possible derivative of benzoate-borane as
condition. So, a mixture of benzaldehyde (1 eq.) and an active reductant may form in situ under reaction
acetophenone (1 eq.) was prepared. The reaction conditions.The benzoate-borane specie is generated
mixture was treated with 1.25 equivalents of NaBH4 by the nucleophilic attack of benzoate ion on borane
and 2 equivalents of PhCO Na in 3 mL water at room (scheme 4, II) that formed from sodium borohydride
2
temperature, as shown in scheme 2.After 60 min, we in water (scheme 4, I). The benzoate-borate is less
have observed that the reduction of benzaldehye to reactive than NaBH and diminishes reactivity.
4
benzylalcohols was completed but acetophene was
intact material, i.e. the competition for reduction was
ExPERIMENTAL
favor of benzaldehyde.
general
The efficiency of this protocol was examined
All substrates and reagents were purchased
by the reduction of a variety of aromatic aldehydes from commercially sources with the best quality. IR
1
(
Table 2, entry 1-11) and aliphatic aldehydes (Table and H NMR spectra were recorded on PerkinElmer
2, entry 14-15) in the presence of structurally different FT-IR RXI and 300 MHz Bruker spectrometers,
ketones (aliphatic and aromatic).All reductions were respectively. The products were characterized by
1
completed within 20-100 min as shown in table their H NMR or IR spectra and comparison with
2
. 1.25 molar equivalents of NaBH and 2 molar authentic samples (melting or boiling points).Organic
4
equivalents of PhCO Na per one equivalents of the layers were dried over anhydrous sodium sulfate. All
2
aldehyde were sufficient to complete conversion of yields referred to isolated pure products.The purity of
1
aldehydes to the corresponding alcohols in excellent products was determinate by H NMR.Also, reactions
yields (90-95%).
are monitoring over silica gel 60 F254 aluminum sheet.
Sonication was carried out using a Cole Palmer high
Also, We have investigated the possibility intensity ultrasonic processor (600W, 20 KHz) via a
of the 1,2-reduction of a,b-unsaturated aldehydes micro-tip probe and 50% amplitude.
(Table 2, entry 12-13) in presence of a,b-unsaturated
ketones with NaBH /PhCO Na/H O/U.S.system.The A typical Procedure for Reduction of aldehydes
4
2
2
reduction of cinnamaldehyde and citral by 1.25 molar with NaBH /PhCO Na/H O/U.S. system
4
2
2
equivalents of NaBH in the presence of 2 molar
In a round-bottomed flask (10 mL) equipped
4
equivalents of PhCO Na carried out exclusively in with a magnetic stirrer, a solution of NaBH (0.047
2
4
1
,2-reduction manner within 60-40 minutes at room g, 1.25 mmol) and PhCO Na (0.138 g, 2 mmol)
2
temperature. In this reaction, the corresponding in water (3 mL) was treated with benzaldehyde
NaBH (1 mmol), H O (3 mL)
2
4
CHO
mmol
CH OH
2
RT, 90 min., Conversion, 100<%
NaBH (1.25 mmol), H O (3 mL)
4
2
1
PhCO Na (2 mmol), U.S.
2
RT, 60 min., Conversion, 100%
Scheme 1

MIRTAGHIꢀADEH & SETAMDIDEH, Orient. J. Chem., Vol. 32(3), 1539-1543 (2016)
1541
(
0.106 g, 1 mmol) in one portion. The mixture was
A typical Procedure for Competitive Reduction
of aldehydes and ketones with NaBH /PhCO Na/
stirred and irradiated with ultrasound waves at
room temperature for 60 minutes. Completion of
the reaction was monitored byTLC (Hexane/EtOAc:
4
2
H O/U.S. system
2
In a round-bottomed flask (10 ml) equipped
with a magnetic stirrer, a solution of benzaldehyde
(0.106 g, l mmol) and acetophenone (0.120 g,
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 Na SO .
(
1 mmol) in H O (3 mL) was prepared.To this solution,
2
4
2
Evaporation of the solvent afforded the pure benzyl
alcohol (0.097 g, 90%).
NaBH (0.047 g, 1.25 mmol) and PhCO Na (0.138
g, 2 mmol) was added.The mixture was stirred and
4
2
CH OH
2
CH(OH)CH
3
NaBH (1mmol)
4
+
RT. 90 min., H O (3mL)
2
Conversion: 100<%
Yield: 80%
0>%
10%
CHO
mmol
COCH
3
+
1
1 mmol
CH OH
2
CH(OH)CH
3
NaBH (1.25 mmol)/PhCO Na (2 mmol)
2
4
+
RT. U.S., 60 min., H O (3mL)
2
Conversion: 100%
Yield: 90%
0%
0%
Scheme 2
Ph
Ph
O
O
Ph
OH 90%
OH 0%
H
NaBH (1.25 mmol)/PhCO Na (2 mmol)
4 2
+
+
RT. U.S., 60 min., H O (3mL)
2
Ph
Ph
Ph
Scheme 3
RCHO
NaOH + H2
BH3
H O
2
PhCO Na
2
O
(
Na
III)
(I)
(II)
RCH OH
2
C
NaBH4
BH3
Ph
O
Scheme 4

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MIRTAGHIꢀADEH & SETAMDIDEH, Orient. J. Chem., Vol. 32(3), 1539-1543 (2016)
Table 1:The optimiꢂation reaction condition for the reduction of
benꢂaldehyde (1 mmol) to benꢂylalcohol in water (3 mL) at room
temperature and under ultrasonic irradiation
Entry
NaBH4
PhCO Na
(mmol)
Time
(min)
Condition Conversion
(%)a
2
(mmol)
1
2
3
4
5
6
7
8
9
1
1
1
1.5
2
2
1
1
0.5
1.25
1.5
1.25
0
1
2
2
2
3
1
2
2
2
2
3
90
90
90
90
90
90
90
90
90
60
50
50
RT
RT
RT
RT
RT
100<
100<
100<
100<
100<
100<
100<
100
RT
b
RT/U.S.
RT/U.S.
RT/U.S.
RT/U.S.
RT/U.S.
RT/U.S.
b
100<
100
100
1
1
1
0
1
2
100
a
b
Conversion monitored byTLC and refer to isolated pure product. Sonication was carried
out using a Cole Palmer high intensity ultrasonic processor (600W, 20 KHz) via a micro-tip
probe and 50% amplitude.
Table 2:The Reduction of Aldehydes (1 eq.) vs. Ketones (1 eq.) by NaBH (1.25 eq.)/PhCO Na (2
4
2
mmol) in Water (3 mL) at Room Temperature under ultrasonic irradiation.a
Ketonesb
Time/min.c
Yield /%
d
Entry Aldehydes
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
benzaldehyde
benzaldehyde
benzaldehyde
Acetophenone
benzophenone
4-phenycyclohexanone
Acetophenone
benzophenone
4-phenycyclohexanone
benzophenone
4-phenycyclohexanone
Acetophenone
benzophenone
4-phenycyclohexanone
chalcone
60
60
60
60
80
40
60
90
85
100
90
40
30
20
20
92
90
95
90
91
90
90
93
95
90
95
90
90
94
92
4-bromobenzaldehyde
3-methylbenzaldehyde
4-nitrobenzaldehyde
4-bromobenzaldehyde
4-methylbenzaldehyde
3-methoxylbenzaldehyde
2-methoxylbenzaldehyde
4-methoxybenzaldehyde
cinnamaldehyde
citral
0
1
2
3
4
5
chalcone
2-pantanone
4-phenycyclohexanone
butanal
hexanal
a
Sonication was carried out using a Cole Palmer high intensity ultrasonic processor (600W, 20 KHz) via a micro-tip
b
c
probe and 50% amplitude. The reduction of ketones vs. aldehydes was 0%. The reaction times refer to complete
d
reduction of aldehydes to their corresponding alcohols. Yields refer to isolated pure alcohols obtained from reduction
of aldehydes.

MIRTAGHIꢀADEH & SETAMDIDEH, Orient. J. Chem., Vol. 32(3), 1539-1543 (2016)
1543
irradiated with ultrasound waves at room temperature
for 60 minutes. TLC monitored the progress of
reaction. After 60 min, the reaction mixture was
quenched by addition of distilled water (5 ml) and
this mixture was then stirred for an additional 1 min.
The mixture was extracted with CH Cl (5×10 ml)
alcohols in high to excellent yields at room
temperature. Reduction reactions were carried out
with 1.25 molar equivalents of NaBH in the presence
4
of 2 molar equivalents of PhCO Na in water as green
2
solvent. In addition, regioselectivity of this system
was also investigated with exclusive 1,2-reduction
of conjugated enals to their corresponding allylic
alcohols in excellent yields. All reductions were
accomplished with high efficiency of the reductions,
2
2
and dried over anhydrous sodium sulfate.
Evaporation of the solvent and short column
chromatography of the resulting crude material over
silicagel by eluent of Hexane/EtOAc: 9/1 affords the
pure liquid benzyl alcohol (0.099 g, 92%) as a sole
product of reduction and acetophenone as an intact
material (table 2, entry 1).
using the appropriate molar ratios of NaBH and
4
PhCO Na, convenient reaction times (20-100 min)
2
under green chemistry protocol, and easy work-up
procedure.
ACKNOWLEꢀgMENTS
CONCLUSION
The authors gratefully appreciated the
financial support of this work by the research council
of Islamic Azad University branch of Mahabad.
In this context, we have been shown
that NaBH /PhCO Na/H O/U.S reduces a variety
4
2
2
of aldehydes vs. ketones to their corresponding
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