2665
In continuation of our work on applications of indium,9 we report a mild and efficient method for
the deoxygenation of amine-N-oxides using indium metal in aqueous methanolic ammonium chloride
(Scheme 1). Furthermore, deoxygenations of pyridine-N-oxides with chlorine containing dehydrating
reagents such as PCl5, POCl3, SO2Cl2 and SOCl3 etc. suffer serious drawbacks such as chlorination of
the pyridine nucleus.7 Several amine-N-oxides are selectively deoxygenated to the corresponding amines
by simply heating the substrate with indium powder in aqueous methanolic ammonium chloride;10 the
results are summarised in the Table 1. In general, the reactions were very clean, high-yielding and
complete within 3–5 h and gave the corresponding amines in good to quantitative yields. The reaction
conditions are compatible with other functional groups such as halides, carboxylic acids, nitriles, ethers
and sulphones.
In conclusion, we have described a mild and efficient method for the selective reduction of amine-
N-oxides to amines using metallic indium in neutral aqueous media. Because of the mild reaction
conditions, our method is compatible with other functional groups present in the molecule, and may
find application in organic synthesis.
Acknowledgements
BVS and MMR are thankful to CSIR and UGC, New Delhi for the award of fellowship.
References
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2. (a) Tjomas, K.; Jerchel, D. Angew. Chem. 1958, 70, 731. (b) Aoyagi, Y; Abe, T.; Ohta, A. Synthesis 1997, 891. (c) Bocker,
R. H.; Guengerich, F. P. J. Med. Chem. 1986, 29, 1596.
3. Sim, T. B.; Ahn, J. H.; Yoon, N. M. Synthesis 1995, 324 and references cited therein. (b) Loev, B.; Snader, K. M. J. Org.
Chem. 1965, 30, 1914.
4. Balick, R.; Kaczmarek, L.; Malinowski, M. Synth. Commun. 1989, 19, 897.
5. Akita, Y.; Misu, K.; Watanabe, T.; Ohta, A. Chem. Pharm. Bull. 1976, 24, 1839.
6. Handa, Y.; Inanga, J.; Yamguchi, M. J. Chem. Soc., Chem. Commun. 1989, 298.
7. (a) Abrovitch, R. A.; Saha, J. G. Adv. Heterocycl. Chem. 1966, 6, 229. (b) Grimmett, M. R. Adv. Heterocycl. Chem. 1993,
58, 271. (c) Morimoto, Y.; Kurihara, H.; Yokoe. C.; Kinoshita, T. Chem. Lett. 1989, 829.
8. (a) Li, C. J.; Chan, T. H. Tetrahedron Lett. 1991, 32, 7017. (b) Cintas, P. Synlett 1998, 1028. (c) Ranu, B. C.; Dutta, P.;
Sankar, A. Tetrahedron. Lett. 1998, 39, 9557. (d) Li, C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149.
9. (a) Sampath Kumar, H. M.; Subba Reddy, B. V.; Tirupathi Reddy, P.; Yadav, J. S. Tetrahedron Lett. 1999, 40, 5387. (b)
Sampath Kumar, H. M.; Subba Reddy, B. V.; Anjaneyulu, S.; Yadav, J. S. Tetrahedron Lett. 1999, 40, 8305–8306.
10. Experimental procedure: A mixture of the amine-N-oxide (5 mmol), indium powder (6 mmol) and saturated ammonium
chloride (10 ml) in ethanol (15 ml) was refluxed for an appropriate time (Table 1). After complete conversion, as indicated
by TLC, the reaction mass was filtered through Celite and washed with ether (2×30 ml). The organic layer was washed with
water and dried over Na2SO4. Evaporation of the solvent in vacuo gave the corresponding amine in pure form. Representative
data for compound 2f: (solid) m.p. 62–63°C, 1H NMR (CDCl3): δ 0.8 (t, 6H, J=8.1 Hz), 2.6 (s, 6H), 3.95 (q, 4H, J=8.1 Hz),
7.1–7.35 (m, 5H). 13C: δ 13.27 (-CH2-CH3), 22.62 (-CH3), 61.04 (-CH2-CH3), 126.52, 126.66, 127.53, 127.69, 127.86,
128.19, 136.20, 136.21, 145.90, 155.10, 155.27, 168.15, 168.10 (aromatic, pyridine and carbonyl carbons). EI-MS: m/z (%)
327 (M+) (100) 282 (70), 254 (50), 236 (60), 209 (30), 180 (15), 139 (40), 105 (15), 83 (80), 77 (5), 47 (40). Compound 1f:
1H NMR (CDCl3): δ 0.75 (t, 6H, J=8.1 Hz), 2.52 (s, 6H), 3.85 (q, 4H, J=8.1 Hz), 6.9–7.2 (m, 5H). EI-MS: m/z 343 (M+),
327 (M−16), 282, 254, 236, 209, 105, 77. Compound 2l: m.p. 78–80°C. 1H NMR (CDCl3): δ 2.42 (s, 3H, -N-CH3), 2.65 (t,
2H, Ar-C2-CH2-N-), 2.85 (t, 2H, Ar-CH2-CH2-N), 3.5 (s, 2H, Ar-CH2-N), 3.85 (s, 6H, OCH3), 6.45 (s, 1H, aromatic), 6.55
(s, 1H, aromatic). EI-MS: m/z 207 (M+), 165 (M−43). Compound 1l: 1H NMR (DMSO): δ 2.35 (s, 3H, N-CH3), 2.55 (t,
2H, Ar-CH2-CH2-N), 2.75 (t, 2H, Ar-CH2-CH2-N), 3.36 (s, 2H, Ar-CH2-N), 3.8 (s, 6H, -OCH3), 6.35 (s, 1H, Ar-H), 6.45
(s, 1H, aromatic). EI-MS: m/z 223 (M+), 207, (M−16).