Efficient reducing system based on iron for conversion of nitroarenes to anilines

Article abstract of DOI:10.1080/00397910903009455

Reduction of nitroarenes with low solubility in EtOH-H2O to anilines easily occurs in a Fe-NH4Cl-acetone-H2O system, and treatment of the same nitroarenes with Fe-NH₄Cl-EtOH-H₂O hardly furnished the corresponding products. Under the reaction condition, the reducible or hydrolysable groups are not affected.

Full text of DOI:10.1080/00397910903009455

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Efficient Reducing System Based on Iron
for Conversion of Nitroarenes to Anilines
Zhu-Ping Xiao a , Ying-Chun Wang a , Gao-Yu Du a , Jun Wu a , Tao
Luo a & Shou-Fu Yi a
a College of Chemistry and Chemical Engineering, Jishou University,
Jishou, China
Version of record first published: 04 Feb 2010.
To cite this article: Zhu-Ping Xiao , Ying-Chun Wang , Gao-Yu Du , Jun Wu , Tao Luo & Shou-Fu Yi
(2010): Efficient Reducing System Based on Iron for Conversion of Nitroarenes to Anilines, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:5, 661-665
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Synthetic Communications1, 40: 661–665, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903009455
EFFICIENT REDUCING SYSTEM BASED ON IRON FOR
CONVERSION OF NITROARENES TO ANILINES
Zhu-Ping Xiao, Ying-Chun Wang, Gao-Yu Du, Jun Wu,
Tao Luo, and Shou-Fu Yi
College of Chemistry and Chemical Engineering, Jishou University,
Jishou, China
Reduction of nitroarenes with low solubility in EtOH–H2O to anilines easily occurs in
a
Fe–NH4Cl–acetone–H2O system, and treatment of the same nitroarenes with
Fe–NH4Cl–EtOH–H2O hardly furnished the corresponding products. Under the reaction
condition, the reducible or hydrolysable groups are not affected.
Keywords: Aniline; Fe–NH4Cl–acetone–H2O; nitroarene; reduction
Aromatic amines are versatile synthetic intermediates in the preparation of
important chemicals such as dyes and pharmaceutical chemicals. Numerous methods
have been reported in the literature for the reduction of nitroarenes to anilines.[1]
Many reductive agents have been recommended for this transformation, and the
most commonly used methods utilize iron,[2,3] such as Fe–AcOH, and zinc,[4,5] such
as Zn–HCl and Zn–NH4Cl. In comparison with other reducing reagents, Fe–NH4Cl
is a mild, neutral, and selective reducing system and finds wide application in organic
synthesis because of its ready availability, ease of handling, and low cost.
Selective methods for the reduction of the nitro group in the presence of other
reducible functional groups are highly desirable. In a development program, we
needed to find an efficient method for the reduction of aromatic nitro compounds
bearing halogen or cyano groups to the corresponding anilines.[6,7] When reduction
of nitro compound 1 (Fig. 1) was run in water by using Zn–HCl, we found that a
bromide was reduced simultaneously. We next studied this reduction using Fe–
NH4Cl in H2O–EtOH or H2O–MeOH, which is a typical procedure for reduction
of aromatic nitro compounds.[8,9] However, the reduction was incomplete even at
reflux for a day because of the poor solubility of compound 1. One interesting obser-
vation was that the conversion of the starting material was not consistent from run
to run. This promoted us to study the effect of acetone, and we realized better yields
without affecting bromides. To widen the synthetic utility of the reagent and
conditions, many nitro aryls are tested. The high yields of the reduction products
demonstrate the efficiency of this new method.
Received March 23, 2009.
Address correspondence to Zhu-Ping Xiao, College of Chemistry and Chemical Engineering,
Jishou University, Jishou 416000, China. E-mail: xiaozhuping2005@163.com
661

662
Z.-P. XIAO ET AL.
Figure 1. The chemical structure of compound 1.
RESULTS AND DISCUSSION
We herein report a mild, neutral, efficient, and selective reducing system,
Fe–NH4Cl–acetone, to convert nitroarenes to anilines (Scheme 1). This system is
especially suitable for conversion of an aromatic nitro compound with poor solu-
bility in ethanol (EtOH) to the corresponding amine. For the first try, we worried
that the resulting aniline would condense with acetone to form a Schiff base in situ.
Fortunately, this was not a problem, and the desired product was obtained in good
to high yield. Tetrahydrofuran is also a suitable solvent except for acetone. To inves-
tigate how wide the ranges of structural variations in reactant molecules could be
tolerated by the reaction, eight substituents (Br, OH, OMe, OBn, CO2Et, CH2CN,
PhSO3, and CH2CO2Et) were used. These substituents were selected primarily for
their wide range of electronic and reducible properties. The results are summarized
in Table 1. The functional group tolerance of this method is evident from entries 1–11,
Table 1. Reduction of aromatic nitro compounds by Fe-NH4Cl in water-acetone
Entry
R1
R2
R3
R4
Mp (ꢀC)
Ref.
Yield (%)
1
2
H
F
CO2Me
CH2CN
CH2CO2Me
H
H
H
Liquid
112–113
48–49
186–187=760 torr[10]
79
87
91
85
86
94
80
92
85
67
98
90
93
H
111–112[11]
3
H
H
47–49[12]
240–250=17 torr[13]
4
H
CH2CO2Me
CH2CO2Me
H
Liquid
81–83
5
H
OH
OMe
—
151–152=1 torr[14]
New
6
H
OH
H
Liquid
155–157
154–156
191–193
65–67
7
PhSO3
PhSO3
Br
PhSO3
PhSO3
Br
8
OMe
OH
New
9
191.5–192.5
66
—
61–62[15]
54–55[16]
10
11
12
13
Br
Br
OMe
OBn
Br
Br
106–107
62–63
53–54
H
OMe
OBn
H
H
H

IRON–AMMONIUM CHLORIDE–ACETONE/TETRAHYDROFURAN
663
Scheme 1. Schematic diagram showing the transformation of aromatic nitro compounds anilines in
acetone (THF)-water solvent system.
which show that halogen, hydroxy, methoxy, sulfonate, ester, and cyano groups are
unaffected under the reaction conditions. In particular, haloaromatic nitro com-
pounds showed remarkable selectivity to give the anilines without any further deha-
logenation.
A solid product is easy to crystallize from AcOEt–petroleum ether. As for a
liquid product, the crude aniline is dissolved in hydrochloric acid (15%, v=v). After
washing with AcOEt, the acid layer is alkalized with NaOH and extracted with
AcOEt. The organic layer is subsequently neutralized and dried. A product with high
purity is given after removal of solvent.
In conclusion, we have developed a simple and general procedure to convert
an aromatic nitro compound to the corresponding amine. This method is especially
suitable for reducing the aromatic nitro compounds with poor solubility in EtOH.
Reducible functional groups such as halogen and CN as well as hydrolyzable
groups such as ester and suflonate groups are unaffected under the reaction
conditions.
EXPERIMENTAL
All chemicals (reagent grade) used were purchased from Aldrich (USA) and
Sinopharm Chemical Reagent Co., Ltd. (China). Melting points (uncorrected) were
determined on an XT4 MP apparatus (Taike Corp., Beijing, China).
Electron-impact (EI) mass spectra were obtained on a Waters GCT mass spec-
1
trometer, and H NMR spectra were recorded on a Bruker AV-500 spectrometer
at 25ꢀC with tetramethylsilane (TMS) and solvent signals allotted as internal stan-
dards. Chemical shifts were reported in parts per million (d). Elemental analyses
were performed on a CHN-O-Rapid instrument and were within ꢁ0.4% of the
theoretical values.
General Procedure for Reduction
Reduced iron powder was added was added to a solution of ammonium chlor-
ide (15 mmol) in water (10 mL) under a nitrogen atmosphere. To this stirring mix-
ture, a solution of nitrocompound (5 mmol) in acetone (25 mL) was added
dropwise. It was refluxed in an oil bath for 2–5 h (TLC monitering; see Table 1).
When the reaction was over, the result was extracted with AcOEt, and the combined
organic layer was basified by adding a saturated solution of NaHCO3. After the
mixture was washed and dried, the solvent was removed under reduced pressure.
The amino compound was further purified as mentioned previously.

664
Z.-P. XIAO ET AL.
Selected Data
5-Amino-2-hydroxy-1,3-phenylene dibenzenesulfonate (7). White pow-
1
der. H NMR (300 MHz, d6-DMSO): 5.09 (bs, 2H), 6.33 (s, 2H), 7.63 (t, J ¼ 7.5 Hz,
4H), 7.79 (t, J ¼ 7.3 Hz, 2H), 7.82 (d, J ¼ 7.5 Hz, 4H), 8.61 (s, 1H); EIMS m=z 421
(Mþ). Anal. calcd. for C18H15NO7S2: C, 51.30; H, 3.59; N, 3.32; S, 15.22. Found:
C, 51.37; H, 3.58; N, 3.31; S, 15.27.
5-Amino-2-methoxy-1,3-phenylene dibenzenesulfonate (8). White pow-
der. 1H NMR (300 MHz, d6-DMSO): 3.25 (s, 3H), 5.49 (bs, 2H), 6.33 (s, 2H), 7.68 (t,
J ¼ 8.0 Hz, 4H), 7.81 (t, J ¼ 7.7 Hz, 2H), 7.85 (d, J ¼ 8.1 Hz, 4H); EIMS m=z 435
(Mþ). Anal. calcd. for C19H17NO7S2: C, 52.40; H, 3.93; N, 3.22; S, 14.73. Found:
C, 52.36; H, 3.92; N, 3.24; S, 14.76.
ACKNOWLEDGMENT
The work was financed by Grant No. JSDXKYZZ0801 from Jishou University
for talent introduction, Hunan Province, China, and by a project (JSU-CX-2009-42)
of College Students’ Research-Type Learning and Innovative Experiment from
Jishou University, Hunan, China.
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