6
704
E. Diez-Cecilia et al. / Tetrahedron Letters 52 (2011) 6702–6704
Table 3
Reduction of common nitro intermediates using the optimized conditions (2 mL
NH NH , 5 equiv KOH, 135 °C in a pressure tube, 24 h)
seem to suggest that the reduction of the nitro group proceeds via
a nitroso intermediate.
From these experiments a mechanism for the reduction of the
2
NO group through reaction with hydrazine can be proposed
2
2
Substrate
Product
Yielda (%)
(Scheme 3).
Cl
Cl
The first step of this reaction would involve nucleophilic attack
9
9
8
3
of hydrazine on the nitro N atom to form a 1-hydroxy-1-aryltriaz-
ane 1-oxide. Attack of a hydroxyl anion results in the formation of
a nitroso intermediate and the release of diazene and water. A sec-
ond hydrazine molecule can attack the nitroso derivative to yield a
1-hydroxy-1-aryltriazane which would undergo transformation
into the anilino derivative, water, and nitrogen. This hypothesis
is in agreement with the lack of reactivity of the hydroxylamine
derivative 5 and the positive results obtained with the nitroso
compound 3. In addition, this mechanism would explain why the
reduction of derivatives 3 and 4 could be performed in the absence
of KOH.
The first objective of this project was to develop a methodology
for the reduction of a problematic diaryl carbonyl 1b to the corre-
sponding diaryl alkane. In the process we achieved not only this
reduction but also the simultaneous reduction of two aryl-nitro
groups to the corresponding anilines 1a. This method of double
reduction proved to be applicable to a variety of molecules and is
a valuable route to alkyl-substituted anilines.
NO2
NH2
2
N
N
O
N
3
NH2
O N
H N
2
2
1
00
0
N3
NH2
Cl
4
Cl
OH
O N
N
H
H2N
NH2
2
5
a
Isolated yield of purified compound.
NH2
H N
2
H+
O
O
O
O
Ar
N
Ar
N
O H
NH2
Ar
O
N
OH
H
NH2
Acknowledgements
N
N
transfer
2
The authors are grateful to the IRCSET (E.D.C.) and HEA-PRTLI-4
(B.K.) for the financial support, and are indebted to Dr. John O’Brien
for NMR studies.
O
N
NH
HN
Ar
NH2
Ar
N
N
H
OH
H O
2
Supplementary data
NH2
H+
O
N
O
N
OH
N
N
H
2
H N
Ar
Ar
Ar
H N NH2 transfer
2
NH2
H O
2
H
References and notes
Ar
N
Ar
N
Ar NH2
H
N
N
N
N
H
1. Clemmensen, E. Chem. Ber. 1913, 46, 1837.
2. Kishner, N. J. Russ. Chem. Soc. 1911, 43, 582.
OH
H
3
4
.
.
Todd, D. Org. React. 1948, 4, 378.
Mozingo, R.; Wolf, D. E.; Harris, S. A.; Folkers, K. J. J. Am. Chem. Soc. 1946, 65,
Scheme 3. Proposed mechanism for the reduction of the nitro group using
1013.
hydrazine.
5.
6.
7.
8.
9.
Allen, C. F. H.; VanAllan, J. Org. Synth. Coll. Vol. 3 1955, 63.
Burdon, J.; Price, R. C. J. Chem. Soc., Chem. Commun. 1986, 893.
Dewar, M. J. S.; Mole, T. J. Chem. Soc. 1956, 2556.
Kuhn, L. P. J. Am. Chem. Soc. 1951, 73, 1510.
Raney M., U.S. Patent 1,628,190, 1927; Chem. Abstr. 1927, 21, 17120.
The corresponding amine was obtained from both compounds 3
and 4 but not from the hydroxylamine 5. Furthermore, to confirm
that hydrazine was involved in the reductive process, derivatives 2,
10. Binz, A.; Schickh, O. V. Chem. Ber. 1935, 68, 315.
1
1
1
1. Cope, O. J.; Brown, R. K. Can. J. Chem. 1961, 39, 1695.
2. Durham, L. J.; McLeod, D. J.; Cason, J. Org. Synth. Coll. Vol. 4 1963, 510.
3. Ung, S.; Falguieres, A.; Guy, A.; Ferroud, C. Tetrahedron Lett. 2005, 46, 5913.
3
, and 4 were reacted in its absence under the same conditions and
no reduction was observed. In addition, reactions were carried out
with hydrazine but without hydroxide, and reduction of the nitro 2
and nitroso 3 compounds was observed. Importantly, the azide
derivative 4 was not reduced under these conditions. These results
14. Wu, G.; Zhu, J.; Mo, X.; Wang, R.; Terskikh, V. J. Am. Chem. Soc. 2010, 132, 5143.
15. Samet, A. V.; Kislyi, K. A.; Marshalkin, V. N.; Strelenko, Y. A.; Nelyubina, Y. V.;
Lyssenko, K. A.; Semenova, V. V. Russ. Chem. Bull. Int. Ed. 2007, 56, 2089.