Chemistry Letters Vol.35, No.2 (2006)
227
Table 1. Reduction of aromatic nitro compounds under ultra-
sound using Zn/HCOONH4/CH3CN systema
(controlled by adding ice to the water bath). When the starting
aromatic nitro compound had completely reacted (monitored
by TLC), the suspension was poured into ice water and extracted
with dichloromethane (4 Â 150 mL). The extract was washed
with brine and dried over anhydrous Na2SO4. Then, it was
concentrated under reduced pressure and a temperature never ex-
ceeding 15 ꢀC to give the corresponding N-arylhydroxylamine.
NO2
NHOH
))))
Zn/HCO2NH4,CH3CN,25-30°C
R1
R1
R2
R2
Yieldb
/%
Purityc
/%
References
Time
/min
Entry
R1
R2
1
2
3
K. S. Suslick, D. A. Hammerton, R. E. Cline, J. Am. Chem.
Soc. 1986, 108, 5641.
W. T. Richards, A. L. Loomis, J. Am. Chem. Soc. 1927, 49,
3086.
1
2
3
4
5
6
7
H
CN
H
Cl
H
COCH3
H
CN
50
100
55
60
55
97
95
94
97
98
94
96
>98
>98
>96
>93
>93
>92
>90
a) R. Ding, C. H. Zhao, Y. J. Chen, L. Liu, D. Wang, C. J. Li,
Tetrahedron Lett. 2004, 45, 2995. b) J. Touster, A. J. Fry,
Tetrahedron Lett. 1997, 38, 6553. c) G. A. Heropoulos, S.
Georgakopoulos, B. R. Steele, Tetrahedron Lett. 2005, 46,
2469. d) T. J. Mason, J. L. Luche, in Chemistry under
Extreme or Non-Classical Conditions, ed. by R. V. Eldik,
C. D. Hubbard, Wiley, New York, 1997, pp. 317–380.
a) R. M. Coates, C. W. Hutchins, J. Org. Chem. 1979, 44,
4742. b) J. Fujiwara, Y. Fukutani, H. Sano, K. Maruoka,
H. Yamamoto, J. Am. Chem. Soc. 1983, 105, 7177.
N. R. Ayyangar, K. C. Brahme, M. S. Shingare, K. V.
Srinivasan, Indian J. Chem. 1989, 28B, 961.
A. D. Mcgill, W. Zhang, J. Wittbrodt, J. Wang, H. B.
Schlegel, P. G. Wang, Bioorg. Med. Chem. 2000, 8, 405.
a) O. Kamm, Org. Synth. 1941, Coll. Vol. I, 445. b) R. J.
Cummings, M. F. Grundon, A. C. Knipe, A. S. Wasfi, J.
Chem. Soc., Perkin Trans. 2 1983, 105. c) C. V. Deliwala,
S. Rajagopalan, Proc.-Indian Acad. Sci., Sect. A 1950, 31,
185.
Cl
CO2C2H5
H
CH3
Cl
H
60
70
aSubstrate:Zn:HCOONH4 = 2.5:10:25 (molar ratio). bYields
of crude products were based on the single experiment and
c
were not optimized. Estimated by 1H NMR analysis.
4
Ar-NO2
O
Ar-NO
Ar-NHOH
Ar-NH2
5
6
7
Ar-N=N-Ar
Ar-N=N-Ar
Scheme 2.
Ar-NH-NH-Ar
ly and a small quantity of nitro compound still could be detected
by TLC even after 12 h. Therefore, the influence of the ultra-
sound on enhancing the reaction rate was very obvious.
Scheme 2 gave the known reduction mechanism of a nitro
group to an amino group.8,14 The reduction underwent two mid-
dle stages and produced nitroso and hydroxylamine intermedi-
ates. The hydroxylamine was converted into amine finally.
Moreover the azoxy, azo, and hydrazo compounds could be
formed very easily when the reduction was performed under
basic condition. Owing to the existence of traces of azoxy,
azo, and amine compounds in our reaction mixture, we believed
that the reaction mechanism of our experiments was the same as
that in the literature14 (Scheme 2).
In conclusion, we reported here an approach for the prepara-
tion of N-arylhydroxylamines from the corresponding aromatic
nitro compounds using the Zn/HCOONH4/CH3CN system
under ultrasound. This method was mild, exceedingly efficient,
highly chemoselective, environmentally friendly, and especially
simple compared to the traditional method in which the careful
manipulation was needed. Further studies to optimize reaction
conditions and investigate solvent influence on the chemoselec-
tive reduction are in progress in our laboratory.
`
S. Ung, A. Falguieres, A. Guy, C. Ferroud, Tetrahedron Lett.
2005, 46, 5913.
8
9
a) N. R. Ayyangar, K. C. Brahme, U. R. Kalkote, K. V.
Srinivasan, Synthesis 1984, 938. b) P. Ren, X. Pan, Q. Jin,
Z. Yao, Synth. Commun. 1997, 27, 3497. c) P. Ren, T. Dong,
S. Wu, Synth. Commun. 1997, 27, 1547. d) K. Yanada, H.
Yamaguchi, H. Meguri, S. Uchida, J. Chem. Soc., Chem.
Commun. 1986, 1655. e) C. S. Rondestvedt, T. A. Johnson,
Synthesis 1977, 850. f) I. D. Entwistle, T. Gilkerson, R. A.
W. Johnstone, R. P. Telford, Tetrahedron 1978, 34, 213. g)
S. Uchida, K. Yanada, H. Yamaguchi, H. Meguri, Chem.
Lett. 1986, 1069.
10 a) F. Li, J. Cui, X. Qian, R. Zhang, Chem. Commun. 2004,
2338. b) F. Li, J. Cui, X. Qian, R. Zhang, Y. Xiao, Chem.
Commun. 2005, 1901.
11 T. V. Pratap, S. Baskaran, Tetrahedron Lett. 2001, 42, 1983.
12 A. Kamal, K. S. Reddy, B. R. Prasad, A. H. Babu, A. V.
Ramana, Tetrahedron Lett. 2004, 45, 6517.
13 a) D. C. Gowda, B. Mahesh, S. Gowda, Indian J. Chem.
2001, 40B, 75. b) F. A. Khan, J. Dash, C. Sudheer, R. K.
Gupta, Tetrahedron Lett. 2003, 44, 7783.
14 a) E. D. Brady, D. L. Clark, D. W. Keogh, B. L. Scott,
J. G. Watkin, J. Am. Chem. Soc. 2002, 124, 7007. b) C.
Yu, B. Liu, L. Hu, J. Org. Chem. 2001, 66, 919. c) P.
Baumeister, H. U. Blaser, M. Studer, Catal. Lett. 1997, 49,
219.
General procedure for the preparation of substituted N-aryl-
hydroxylamines is as follows: A mixture of commercial zinc
dust (10 mmol) and aromatic nitro compound (2.5 mmol) in
CH3CN was sonicated at 59 kHz under mechanical stirring at
room temperature for 30 min. Then, to the suspension, was
added all at once HCOONH4 (25 mmol) and the mixture was still
stirred under ultrasonic conditions for 50–100 min at 25–30 ꢀC