Ionic liquid mediated efficient reduction of nitroarenes using stannous chloride under sonication

Article abstract of DOI:10.1016/j.tetlet.2005.04.035

Nitroarenes were rapidly reduced to the corresponding aromatic amines using stannous chloride in ionic liquid as a safe and recyclable reaction medium under sonication. The method is environmentally benign and sensitive functional groups remain unaffected.

Full text of DOI:10.1016/j.tetlet.2005.04.035

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3987–3990
Ionic liquid mediated efficient reduction of nitroarenes
using stannous chloride under sonication
Ganesha Rai,a,b Jae Min Jeong,a,b,c,* Yun-Sang Lee,a,b Hyung Woo Kim,a Dong Soo Lee,a
June-Key Chunga,c and Myung Chul Leea,b
aDepartment of Nuclear Medicine, Seoul National University Hospital, 28 Yungun-dong, Jongro-gu, Seoul 110-744, Republic of Korea
bClinical Research Institute, Seoul National University Hospital, 28 Yungun-dong, Jongro-gu, Seoul 110-744, Republic of Korea
cCancer Research Institute, Seoul National University College of Medicine, 28 Yungun-dong, Jongro-gu, Seoul 110-744,
Republic of Korea
Received 14 March 2005; revised 9 April 2005; accepted 11 April 2005
Abstract—Nitroarenes were rapidly reduced to the corresponding aromatic amines using stannous chloride in ionic liquid as a safe
and recyclable reaction medium under sonication. The method is environmentally benign and sensitive functional groups remain
unaffected.
ꢀ 2005 Published by Elsevier Ltd.
Reduction of aromatic nitrocompounds to the corre-
sponding amines is a synthetically important transfor-
mation,1 both in industry and academic laboratories,
particularly when a molecule has several other reducible
functionalities. Therefore, numerous new reagents and
methods have been developed for reduction of aromatic
nitrocompounds,2 some of which are incompatible with
other substituents or unsafe in view of green chemistry.
Only two papers reported ionic liquid mediated reduc-
tion of nitroarenes using zinc in ammonium salts10 and
samarium.11 Stannous chloride is amongst the popular
reducing agent used for reduction of aromatic nitrocom-
pounds.12 However, no other attempt has been made for
the reduction of nitrocompounds either using stannous
chloride with other additives except NaBH4, which
was reported by Satoh.12b As safer and green technolo-
gies like recyclable media or catalysts are getting more
importance in modern synthetic chemistry, we wish to
report a novel use of ionic liquid for rapid reduction
of nitroarenes under sonication.
Room temperature ionic liquids such as 1-butyl-3-
methylimidazolium tetrafluoroborate ([bmim][BF4])
and 1-butyl-3-methylimidazolium triflate ([bmim][OTf])
are environmentally benign solvents due to their unique
chemical and physical properties such as excellent chem-
ical and thermal stability with ease of reuse, miniscule
vapor pressure, unique miscibility and non-flammabil-
ity.3 They behave like polar aprotic solvents and have
been employed as green solvents for a vast array of or-
ganic and enzymatic transformations,4–6 in liquid–liquid
separation,7 and recycling of organometallic catalysts.8
Further, ionic liquids have also been shown to enhance
the rate of many transformations.9
Reaction of various aromatic nitrocompounds with
stannous chloride in [bmim][BF4] or [bmim][OTf] under
sonication afforded corresponding amines in good to
excellent yields (Scheme 1). The scope and generality
of this method is illustrated with respect to various
nitroarenes are summarized in Table 1. All reactions
were carried out in ionic liquids [bmim][BF4] and
[bmim][OTf] under sonication for 10–15 min at room
NH2
NO2
Keywords: Ionic liquid; Reduction of nitroarene; Stannous chloride;
Sonication.
Ionic liquid, sonication
RT, 10-15 min.
.
SnCl2 2H2O
R
R
+
*
Corresponding author. Address: Department of Nuclear Medicine,
Seoul National University Hospital, 28 Yungun-dong, Jongro-gu,
Seoul 110-744, Republic of Korea. Tel.: +82 2 2072 3805; fax: +82 2
745 7690; e-mail: jmjng@snu.ac.kr
Scheme 1. Reduction of nitroarenes with stannous chloride in ionic
liquid under sonication.
0040-4039/$ - see front matter ꢀ 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.04.035

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G. Rai et al. / Tetrahedron Letters 46 (2005) 3987–3990
Table 1. Reduction of nitroarenes with stannous chloride in [bmim][BF4] and [bmim][OTf] under sonication
Entry
Reactant
Producta
% Yieldb
[bmim][BF4]
87
[bmim][OTf]
96
NH2
NO2
1
Cl
Cl
NO2
NH2
Cl
Cl
2
3
84
98
90
97
NO2
NH2
Br
Br
NO2
NH2
4
92
89
CH3
NO2
CH3
NH2
5
6
91c
89c
OH
OH
NO2
NH2
86c
87c
OH
OH
NO2
NH2
7
8
87
80
89
80
OMe
NO2
OMe
NH2
CH2OH
NO2
CH2OH
NH2
9
47
83
62
89
CHO
CHO
NO2
NH2
10
COCH3
NO2
COCH3
NH2
11
99
86
CN
CN

G. Rai et al. / Tetrahedron Letters 46 (2005) 3987–3990
3989
Table 1 (continued)
Entry
Reactant
Producta
% Yieldb
[bmim][BF4]
88c
[bmim][OTf]
93c
NO2
NH2
12
CO2H
NO2
CO2H
NH2
NH2
13
83c
86c
NO2
NO2
NH2
14
15
88c
92c
94c
96c
N
N
I
I
N
N
NO2
NH2
N
N
a All products were characterized by proton NMR and LCMS analysis (compared with literature values).
b Isolated yields of pure amines.
c Product and ionic liquid were extracted in dichloromethane and separated by column.
temperature. As is evident, the ultrasound-assisted
reduction of the aromatic nitrocompounds with stan-
nous chloride proceeded smoothly at room temperature
with complete conversion in a very short period (TLC
and NMR show the absence of any starting or side
products). We used sonication as a means to achieve effi-
cient mixing and enhance the rate of conversion. With-
out sonication nitroreduction under stirring at room
temperature even after 10 h was sluggish, as viscous
reaction mixture makes mechanical or magnetic stirring
inefficient. The rate enhancement under sonication in
the present protocol may be attributed to cavity effect
and formation of hot spots as reported for many other
kinds of transformations in the literature.13 Sensitive
functional groups like CHO, CN, CH2OH, etc. re-
mained unaffected. Low yield was observed for the
reduction of m-nitrobenzaldehyde due to subsequent
self-condensation leading to formation of higher oligo-
mers. Further, nitroarenes like entries 14 and 15, which
are insoluble or partially soluble in organic solvents, can
also be reduced effectively in good yield. Nitroarenes
were initially dissolved in ionic liquid and sonicated
after adding stannous chloride. Products were extracted
with ether and the remaining ionic liquid was recovered
by extracting with dichloromethane. In case of ether-
insoluble amines, both products and ionic liquid were
extracted with dichloromethane and separated in a col-
umn using n-hexane/ethyl acetate solvent mixture (1:5).
Completion of the reaction was monitored by TLC
and products were characterized by proton NMR and
LCMS data (compared with literature data). The reduc-
tion can also be performed upon heating the reaction
mixture in ionic liquid for 100–120 ꢁC. The transform-
ation was observed to be faster in ionic liquid than in
ethyl acetate or alcohol. In the reduction process, ionic
liquid can be recovered in more than 90% yield after
extracting the product with diethyl ether or dichloro-
methane, which can be reused for the same compounds
to avoid cross contamination (trace amount of amine
contaminant has been observed in some cases). The
reduction of p-nitroacetophenone is representative: p-
nitroacetophenone (165 mg, 1.00 mmol) and [bmim][BF4]
or [bmim][OTf] (1mL) were placed in a 25 mL round-
bottomed flask and sonicated to dissolve the compound.
Stannous chloride (1.128 g, 5 mmol) was added and
sonicated for 10 min (TLC showed the completion of
the reaction). The reaction mixture was neutralized with
sodium bicarbonate and extracted with ether (5 mL · 2).
The combined extract was dried over anhydrous
Na2SO4 and then the solvent was removed under re-
duced pressure to get pure p-aminoacetophenone. Ionic
liquid was recovered by extracting with dichlorometh-
ane and can be reused for the same reduction.
In conclusion, we have found that ionic liquid is a good
reaction medium for rapid reduction of aromatic nitro-
compounds in good yield at room temperature under
sonication. In addition, it can be reused for same reac-
tions and convenient for the reduction of compounds,
which are partially soluble or insoluble in common
organic solvents. Further, this method is simple and
safe from green chemistry point of view.
Acknowledgment
We thank KOSEF for supporting fund (mid- and long-
term project of atomic energy).
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