8810
P. S. Reddy et al. / Tetrahedron Letters 48 (2007) 8807–8810
Based on this result, a series of reactions were conducted
by reacting benzaldehyde, anisaldehyde and tolualde-
hyde with a series of amines: aromatic amines (primary
and secondary), aliphatic amines (cyclic and acyclic) and
aromatic amines with different substituents. For each
type of substrate, the time for maximum formation of
imines was monitored and NaBH4 was added after the
optimized time, see Table 1. All the substrates reacted
smoothly to afford the corresponding amines in good
to excellent yields. The methodology was also extended
for the reductive amination of ketones (Table 1; entries
22–24). The reusability of an IL is always an advantage
for the commercial viability of the process. The recov-
ered ionic liquid was recycled for four consecutive runs
for the reductive amination of benzaldehyde over a
period of 4 h affording 93%, 85%, 83% and 76% yields
of N-benzylaniline.
127.48, 127.54, 128.75, 128.78, 137.67, 139.31, 148.13,
158.79; Anal. Calcd for C12H12N2: C, 78.23; H, 6.57,
N, 15.21. Found: C, 78.69; H, 6.31, N, 15.42; EI-mass:
m/z 184 [M]+, 106 [MÀ78]+, 91, 79.
2.1.2. 4-Chlorophenyl-4-methoxybenzylamine (entry 10).
Yellow solid; mp: 78–81 ꢁC; IR (KBr): m 3409 (NH),
1166 (OCH3) cmÀ1 1H NMR (300 MHz, CDCl3): d
;
3.72 (3H, s), 3.81–3.91 (1H, br s), 4.18 (2H, s), 6.5
(2H, J = 9.06 Hz, d), 6.80 (2H, J = 9.06 Hz, d), 7.0
(2H, J = 9.06 Hz, d), 7.22 (2H, J = 8.30 Hz, d); 13C
NMR (75 MHz, CDCl3): d 47.75, 55.54, 113.55,
113.99, 114.34, 114.53, 121.87, 129.05, 129.43, 130.60,
130.94, 132.00, 146.77, 158.95; Anal. Calcd for
C14H14ClNO: C, 67.88; H, 5.70; N, 5.65. Found: C,
68.75; H, 5.39; N, 5.64; EI-mass: m/z 247 [M]+, 121
[MÀ126]+, 91, 77.
In conclusion, an efficient protocol for reductive amina-
tion of carbonyl compounds using a variety of amines in
a Brønsted acidic IL (HMIm)BF4 has been reported.
The reported protocol is mild, efficient and user and
environmentally friendly. An important aspect of this
protocol is the selectivity of the reducing agent towards
imines without the formation of any side product.
Supplementary data
Supplementary data associated with this article can be
References and notes
2. Experimental
1. Cho, B. T.; Kang, S. K. Tetrahedron 2005, 61, 5725.
2. Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.;
Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61,
3849.
The IL, (HMIm)BF4 was prepared following the
reported procedure.12
3. Imao, D.; Fujihara, S.; Yamamoto, T.; Ohta, T.; Ito, Y.
Tetrahedron 2005, 61, 6988.
4. Menche, D.; Hassfeld, J.; Menche, G.; Ritter, A.;
Rudolph, S. Org. Lett. 2006, 8, 741.
2.1. General procedure for reductive amination
Amine (1.0 mmol) and carbonyl compound (1.2 mmol)
were taken in (HMIm)BF4 (0.17 g; 1.0 mmol) and the
reaction mixture was stirred at 30 ꢁC for 30–60 min fol-
lowed by the addition of sodium borohydride (0.057 g;
1.5 mmol). After completion of the reaction, the reac-
tion mixture was extracted with ethyl acetate
(3 · 10 mL). The combined extracts were dried over
anhydrous Na2SO4 and evaporated. The crude was puri-
fied by silica gel column chromatography eluting with 2–
10% EtOAc in hexane. The IL was solubilized in aceto-
nitrile and filtered to separate sodium borohydride. The
organic layer was evaporated and the IL dried under
vacuum for further reuse. All products were character-
ized by IR, NMR, mass spectrometry and elemental
analysis and compared with those reported in the litera-
ture.1–9,11,15,16 All new compounds gave satisfactory
spectroscopic data in accordance with their structures.
5. Ito, T.; Nagata, K.; Kurihara, A.; Miyazaki, M.; Ohsawa,
A. Tetrahedron Lett. 2002, 43, 3105, and references cited
therein.
6. Ravi, V.; Ramu, E.; Kumar, P. V.; Rao, A. S. Chin. J.
Chem. 2006, 24, 807.
7. Heydari, A.; Khaksar, S.; Akbari, J.; Esfandyari, M.;
Pourayoubi, M.; Tajbakhsh, M. Tetrahedron Lett. 2007,
48, 1135, and references cited therein.
8. Heydari, A.; Khaksar, S.; Esfandyari, M.; Tajbakhsh, M.
Tetrahedron 2007, 63, 3363.
9. Heydari, A.; Arefi, A.; Esfandyari, M. J. Mol. Catal. A:
Chem. 2007, 274, 169, and references cited therein.
10. Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S.
Tetrahedron 2005, 61, 1015.
11. Nagaiah, K.; Kumar, V. N.; Rao, R. S.; Reddy, B. V. S.;
Narsaiah, A. V.; Yadav, J. S. Synth. Commun. 2006, 36,
3345.
12. Zhu, H.-P.; Yang, F.; Tang, J.; He, M.-Y. Green Chem.
2003, 5, 38.
13. Wu, H.-H.; Yang, F.; Cui, P.; Tang, J.; He, M.-Y.
Tetrahedron Lett. 2004, 45, 4963.
14. Wang, H.; Cui, P.; Zou, G.; Yang, F.; Tang, J. Tetra-
hedron 2006, 62, 3985.
15. Sato, S.; Sakamoto, S.; Miyazawa, E.; Kikugawa, Y.
Tetrahedron 2004, 60, 7899.
16. Varma, R. S.; Dahiya, R. Tetrahedron 1998, 54,
6293.
2.1.1. 2-(N-Benzyl)aminopyridine (entry 4). Yellow oil;
IR (neat): m 3377 (NH) cmÀ1 1H NMR (300 MHz,
;
CDCl3): d 4.52 (2H, J = 6.04 Hz, d), 6.50 (1H,
J = 8.3 Hz, d), 6.78–6.90 (1H, br s), 6.55 (1H,
J = 6.04 Hz, t), 7.21–7.28 (5H, m), 7.50 (1H,
J = 6.79 Hz, t), 8.20 (1H, J = 5.28 Hz, d); 13C NMR
(75 MHz, CDCl3): d 46.41, 106.92, 113.17, 127.37,