4
Tetrahedron
blocks in the synthesis of pharmaceuticals and natural products,
suggestive of the potential utility of the reduction protocol.
References and notes
1. (a) Downing, R. S.; Kunkeler, P. J.; Bekkum, H. Catal. Today.
5 equiv Fe/2 N HCl
10 equiv HFIP
NO2
NH2
1997, 37, 121-136; (b) One, N. The Nitro Group in Organic
Synthesis, Wiley-VCH: New York, 2001; (c) Suchy, M.;
Winternitz, P.; Zeller, M. World (WO) Patent 91/00278, 1991.
(a) For a review of selective hydrogenation of nitroarenes, see:
Blaser, H. U.; Steiner, H.; Studer, M. Chem. Cat. Chem. 2009,
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For reviews on transfer hydrogenation, see: (a) Gladiali, S.;
Mestroni, G. In Transition Metals for Organic Synthesis;
Beller, M.; Bolm, C., Eds.; Wiley-VCH: Weinheim, 2004; vol.
4,pp 136-146; (b) Gladiali, S.; Alberico, E. Chem. Soc. Rev.
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rt, 30 min
NC
NC
10.5 g
90%
2.
O
O
O
5 equiv Fe/2 N HCl
10 equiv HFIP
rt, 30 min
O
NO2
3.5 g
NH2
81%
3.
5 equiv Fe/2 N HCl
10 equiv HFIP
O2N
H2N
rt, 30 min
N
Cl
N
Cl
6.0 g
91%
236; (c) Samec, J. S. M.; Bäckvall, J.-E.; Andersson, P. G.;
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S.; Gallou, F;. Lipshutz, B. H. Angew. Chem. Int. Ed. 2016, 55,
9125-9129; (e) Sharma, U.; Kumar, N.; Verma, P. K.; Kumar, V.;
Singh, B. Green Chem. 2012, 14, 2289-2293.
Scheme 1. The gram-scale reduction reactions
It is generally accepted that the direct reduction of
nitrobenzene to aniline proceeds via nitrosobenzene and N-
phenylhydroxylamine intermediates (Scheme 2). We noticed that
hydrogen bond forming mechanisms have been proposed in other
HFIP-promoted reactions.19 We assumed that hydrogen bonding
existing in intermediates I and II would be the driving force for
the removal of water. Thus, the transformation can take place
under very mild conditions. Overall, HFIP can efficiently
promote the nitro reduction reduction as a hydrogen bond donor.
4.
5.
6.
Zhu, K.; Shaver, M. P.; Thomas, S. P. Chem. Sci. 2016, 7,
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Uberman, P. M.; García, C. S.; Rodríguez, J. R.; Martín, S. E.
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R. E.; Grecko, R.; Ran, Y.; Sensintaffar, J. L.; Kamal, A.;
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Synthesis. 2003, 13, 2001-2004.
F3C
CF3
H
H
H
O
O
O
O
OH
O
O
N
N
N
+ 2 e, H+
+ H+
- H2O
R
R
R
F3C
I
CF3
H
O
7.
8.
Kelly, S. M.; Lipshutz, B. H. Org. Lett. 2014, 16, 98-101.
(a) Shuklov, I. A.; Dubrovina, N. V.; Börner, A. Synthesis.
2007, 2007, 2925-2943; (b) Khaksar, S. J. Fluorine Chem.
2015, 172, 51-61; (c) Wang, Y. X.; Li,G. X.; Yang, G. H.; He,
G.; Chen, G. Chem. Sci. 2016, 7, 2679-2683.
H
O
HO
R
O
HO
R
N
N
H
NH
NH
+ 2 e, H+
+ H+
+ H+
R
R
9.
Hofmann, M.; Hampel, N.; Kanzian, T.; Mayr, H. Angew.
Chem. Int. Ed. 2004, 43, 5402-5405.
II
NH
NH2
+ H+
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(b) Champagne, P. A.; Benhassine, Y.; Desroches, J.; Paquin,
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Am. Chem. Soc. 2015, 137, 6140-6143.
+ 2 e
R
R
- H2O
Scheme 2. The reaction pathway for the nitro reduction
Conclusion
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Werbeloff, A.; Shalit, H.; Pappo, D. Angew. Chem. Int. Ed.
2015, 127, 4272-4276.
In conclusion, an efficient and practical method has been
13. Czaplik, W. M.; Grupe, S.; Mayer, M.; Wangelin, A. J. Chem.
Commun. 2010, 46, 6350-6352.
developed for chemoselective reduction of nitro groups, which
was carried out using a combination of iron powder and 2 N HCl
aqueous solution in the presence of HFIP under mild conditions.
The reduction is chemoselective for nitroaromatic compounds
bearing a wide range of reactive functional groups (e.g. aldehyde,
ketone, acid, ester, amide, nitrile, halogens, allyl, propargyl). In
addition, compatibility with common protecting groups and
heteroaromatic substrates has been demonstrated. 1-nitrooctane
was smoothly reduced in good yield. Also, aminaphtone
precursor was achieved successfully.
14. Chowdhury, R. R.; Crane, A. K.; Fowler, C.; Kwong, P.;
Kozak, C. M. Chem. Commun. 2008, 19, 94-96.
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3316-3340.
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9095-9097.
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18. BALDACCI, M.; Roberti, M. US Pat., 2014/0323747A1, 2014.
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10497-10500.
Acknowledgments
This work is supported by Science and Technology
Department of Sichuan Province under grant number
2015JY0171.
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