A facile reduction of aromatic nitro compounds to aromatic amines with bis(cyclopentadienyl)titanium(IV) dichloride-indium system

Article abstract of DOI:10.1081/SCC-120003398

Cp₂TiCl₂/In system was found to be a new reagent for reducing various aromatic nitro compounds to the corresponding aromatic amines in good yields under mild and neutral conditions.

Full text of DOI:10.1081/SCC-120003398

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A FACILE REDUCTION OF AROMATIC NITRO
COMPOUNDS TO AROMATIC AMINES WITH
BIS(CYCLOPENTADIENYL)TITANIUM(IV)
DICHLORIDE–INDIUM SYSTEM
Byung Woo Yoo a , Sung Jae Lee a , Byoung Seung Yoo b , Kyung Il Choi c & Joong Hyup Kim c
a Department of Chemistry , Korea University , Chochiwon, Chungnam, 339-700, Korea
b Department of Food Science and Technology , Dongguk University , Chung-gu, Seoul,
100-715, Korea
c Biochemicals Research Center , Korea Institute of Science and Technology , Cheongryang,
Seoul, 130-650, Korea
Published online: 16 Aug 2006.
To cite this article: Byung Woo Yoo , Sung Jae Lee , Byoung Seung Yoo , Kyung Il Choi & Joong Hyup Kim (2002) A
FACILE REDUCTION OF AROMATIC NITRO COMPOUNDS TO AROMATIC AMINES WITH BIS(CYCLOPENTADIENYL)TITANIUM(IV)
DICHLORIDE–INDIUM SYSTEM, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 32:16, 2489-2493, DOI: 10.1081/SCC-120003398
To link to this article: http://dx.doi.org/10.1081/SCC-120003398
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 16, pp. 2489–2493, 2002
A FACILE REDUCTION OF
AROMATIC NITRO COMPOUNDS
TO AROMATIC AMINES WITH
BIS(CYCLOPENTADIENYL)TITANIUM(IV)
DICHLORIDE–INDIUM SYSTEM
1
2
Byung Woo Yoo,1, Sung Jae Lee, Byoung Seung Yoo,
*
Kyung Il Choi,3 and Joong Hyup Kim3
1Department of Chemistry, Korea University,
Chochiwon, Chungnam, 339-700, Korea
2Department of Food Science and Technology,
Dongguk University, Chung-gu, Seoul, 100-715, Korea
3Biochemicals Research Center, Korea Institute of
Science and Technology, Cheongryang, Seoul,
130-650, Korea
ABSTRACT
Cp2TiCl2/In system was found to be a new reagent for reduc-
ing various aromatic nitro compounds to the corresponding
aromatic amines in good yields under mild and neutral
conditions.
*Corresponding author. E-mail: yoobw@tiger.korea.ac.kr
2489
DOI: 10.1081/SCC-120003398
Copyright & 2002 by Marcel Dekker, Inc.
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2490
YOO ET AL.
The chemical reactivity of Cp2TiCl2/M system (M¼Na, Zn, Al,
Mg, Sm) has been the subject of considerable interest and the reducing
ability of these systems has been extensively studied.[1] It has recently been
reported that Cp2TiCl2/samarium system is used as a reagent for reducing
nitroarenes to the corresponding amines.[2] The synthesis of aromatic
amines has been an active area of research for many years and a large
number of methods have been developed for the reduction of aromatic
nitro compounds.[3] We considered that Cp2TiCl2/In system can be an effi-
cient reducing agent for the conversion of nitroarenes to the corresponding
amines. The application of indium reagents in organic synthesis has
attracted considerable interest in the last decade.[4] We have investigated
the reaction of Cp2TiCl2/In with various nitroarenes and found that they
can be effectively reduced to the corresponding aromatic amines in good
yields (Eq. 1). The scope of the reaction is illustrated in Table 1. The new
reducing system was generated by the addition of indium powder to a stirred
solution of bis(cyclopentadienyl)titanium(IV) dichloride in THFunder
nitrogen. In continuation of our interest on the applications of indium
reagents for various transformations[5] we would like to report here the
reduction of aromatic nitro compounds to aromatic amines by treatment
with Cp2TiCl2/In under mild conditions. Some control experiments revealed
that nitroarenes could not be reduced by Cp2TiCl2 or indium alone and
were recovered unchanged.
Cp2TiCl2=In
ArNO2
1
À! ArNH2
ð1Þ
THF; r: t:
2
The reaction molar ratio of indium and Cp2TiCl2 is 1 : 2. If the molar
ratio is changed to In:Cp2TiCl2 ¼ 1 : 1, the reaction is not successful. In
comparison with the Cp2TiCl2/Sm system, the method of Cp2TiCl2/In
system resulted in high yields of amino compounds (76–91%). The func-
tional group tolerance of this method is evident from Table 1 which shows
that bromo, chloro, methoxy, hydroxy, ketone, carboxyl and ester are not
affected under the reaction conditions. All the compounds obtained showed
IR, NMR and mass spectral data compatible with the structure. In order
to assess the generality of the process, the reaction was studied with a
variety of nitroarenes. Thus, we have been able to demonstrate the utility
of easily accessible Cp2TiCl2/In system as a convenient reagent for
effecting chemoselective reduction of nitroarenes. Although the role
of bis(cyclopentadienyl)titanium(IV) dichloride is still not clarified, it is
assumed that reduction of titanium(IV) with indium provides low valent
titanium,[6] which might be reducing nitroarenes 1 to give the corresponding
amines 2. The notable advantages of this methodology are mild reaction

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REDUCTION OF AROMATIC NITRO COMPOUNDS
2491
Table 1. Reduction of Nitroarenes to Amines with Cp2TiCl2/In
Reaction Time
(h)
Yield
(%)b
Entry
Substrate
C6H5NO2
p-CH3C6H4NO2
p-HOC6H4NO2
p-BrC6H4NO2
o-CH3COC6H4NO2
p-CH3OOCC6H4NO2
o-CH3OC6H4NO2
p-HOOCC6H4NO2
Producta
C6H5NH2
p-CH3C6H4NH2
p-HOC6H4NH2
p-BrC6H4NH2
o-CH3COC6H4NH2
p-CH3OOCC6H4NH2
o-CH3OC6H4NH2
p-HOOCC6H4NH2
1
2
3
4
5
6
7
8
0.5
0.5
3
0.5
0.5
2
91
91
86
90
89
93
79
76
0.5
1
9
0.5
80
10
4
81
aAll products obtained were fully characterized by spectral analysis.
bIsolated yield.
condition, simple operation, high yield, tolerance of various functional
groups on the aromatic ring.
In conclusion, we believe this procedure using Cp2TiCl2/In system will
present a useful and convenient alternative to the existing methods for
reduction of nitroarenes to the corresponding amines. Further applications
of Cp2TiCl2/In system as reducing agent in organic synthesis are currently
under investigation.
EXPERIMENTAL
Tetrahydrofuran was freshly distilled from sodium/benzophenone
1
ketyl before use. H NMR spectra were recorded on a FT-Bruker AF-300
1
(300 MHz for H NMR; 75 MHz for 13C NMR) using TMS as an internal
standard. The solvent was CDCl3 unless otherwise noted. IR spectra were
obtained on a Perkin Elmer 16FPC FT-IR Shimadzu. GC-MS was
recorded on a Hewlett-Packard 5890 GC. High resolution mass spectra
(HRMS) were obtained on a Varian MATCH-50Finstrument.

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2492
YOO ET AL.
General Procedure for the Reaction
Bis(cyclopentadienyl)titanium(IV) dichloride (438 mg, 1.75 mmol,
Aldrich, 97%), indium powder (100 mesh, 86 mg, 0.75 mmol, Aldrich,
99.99%) and THF(5 mL) were mixed under nitrogen atmosphere and the
resulting mixture was stirred at reflux for 30 min. A dark-red solution of the
low-valent titanium–indium complex was obtained and cooled to room tem-
perature. To this solution, nitrobenzene (23.0 mg, 0.25 mmol) was added. The
reaction mixture was stirred for 10 min at room temperature under nitrogen.
The solvent was evaporated under reduced pressure and the residue was
diluted with ether and filtered. The crude product was purified by silica gel
column chromatography (hexane : ethyl acetate ¼ 6 : 1) to afford aniline
(20.0 mg, 91%).
1
Entry 1: Oil. H NMR (CDCl3, 300 MHz): ꢀ 7.23 (t, 2H, J ¼ 8.8 Hz),
6.81 (m, 3H), 3.63 (bs, 2H): IR(film) 3455, 3356, 1606, 1498 cmÀ1; GC-MS
(m/z) 93 (Mþ).
Entry 2[7]: M.p. 45–46ꢀC (lit: 44–46ꢀC). 1H NMR (CDCl3, 300 MHz): ꢀ
6.97 (d, 2H, J ¼ 8.4 Hz), 6.65 (d, 2H, J ¼ 8.4 Hz), 3.38 (bs, 2H), 2.24 (s, 3H);
IR(film) 3416, 3334, 1624, 1514 cmÀ1; GC-MS(m/z) 107 (Mþ).
Entry 3[7]: M.p. 185–187ꢀC (lit: 188–190ꢀC). 1H NMR (CDCl3,
300 MHz): ꢀ 7.23 (d, 2H, J ¼ 8.8 Hz), 6.81 (d, 2H, J ¼ 8.8 Hz), 2.63 (bs,
2H); IR(film) 3340, 3280, 1616, 1508 cmÀ1; GC-MS(m/z) 93 (Mþ).
Entry 4[7]: M.p. 62–64ꢀC (lit: 62–64ꢀC). 1H NMR (CDCl3, 300 MHz): ꢀ
7.23 (d, 2H, J ¼ 8.6 Hz), 6.56 (d, 2H, J ¼ 8.6 Hz), 3.67 (bs, 2H); IR(film)
3466, 3376, 1610, 1486 cmÀ1; GC-MS(m/z) 170 (Mþ).
1
Entry 5: Oil. H NMR (CDCl3, 300 MHz): ꢀ 7.71 (d, 1H, J ¼ 8.4 Hz),
7.26 (t, 1H, J ¼ 8.6 Hz), 6.65 (m, 2H), 6.27 (bs, 2H), 2.57 (s, 3H): IR(film)
3462, 3342, 1644, 1616, 1550 cmÀ1; GC-MS(m/z) 135 (Mþ).
Entry 6[7]: M.p. 109–110ꢀC (lit: 110–111ꢀC). 1H NMR (CDCl3,
300 MHz): ꢀ 7.86 (d, 2H, J ¼ 8.7 Hz), 6.64 (d, 2H, J ¼ 8.7 Hz), 4.06
(bs, 2H), 3.87 (s, 3H); IR(film) 3422, 3340, 1684, 1634, 1596 cmÀ1
;
GC-MS(m/z) 151 (Mþ).
Entry 7: Oil. 1H NMR (CDCl3, 300 MHz): ꢀ 6.76 (m, 4H), 3.85 (s, 3H),
3.67 (bs, 2H); IR(film) 3454, 3370, 1616, 1506, 1224 cmÀ1; GC-MS(m/z)
123 (Mþ).
Entry 8[7]: M.p. 188–189ꢀC (lit: 187–189ꢀC). 1H NMR (CDCl3,
300 MHz):
ꢀ
7.23 (d, 2H, J ¼ 8.8 Hz), 6.81 (d, 2H, J ¼ 8.8 Hz),
3.63 (bs, 2H); IR(film) 3462, 3366, 1690, 1604, 1522 cmÀ1; GC-MS(m/z)
93 (Mþ).
1
Entry 9: Oil. H NMR (CDCl3, 300 MHz): ꢀ 6.98 (d, 1H, J ¼ 7.7 Hz),
6.71 (s, 1H), 6.49 (d, 1H, J ¼ 9.0 Hz), 3.47 (bs, 2H), 2.25 (s, 3H): IR(film)
3445, 3362, 1624, 1500 cmÀ1; GC-MS(m/z) 141 (Mþ).

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REDUCTION OF AROMATIC NITRO COMPOUNDS
2493
Entry 10[7]: M.p. 253–255ꢀC (lit: 253–255ꢀC). 1H NMR (CDCl3,
300 MHz): ꢀ 8.28 (m, 2H), 7.80(m, 3H), 7.48 (t, 1H, J ¼ 9.0 Hz), 6.98
(d, 1H, J ¼ 6.0 Hz), 6.88 (bs, 2H); IR(film) 3455, 3336, 1650, 1610,
1495 cmÀ1; GC-MS (m/z) 223 (Mþ).
ACKNOWLEDGMENT
This work was financially supported by Korea Institute of Science and
Technology (2E16800) and partially by Korea University.
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Received in Japan June 7, 2001

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