H. Alinezhad et al. / Tetrahedron Letters 50 (2009) 659–661
661
10 mmol scale and a similar yield was obtained. We also exam-
Acknowledgments
ined the chemoselective reductive amination of functionalized
benzaldehydes bearing other reducible functional groups employ-
ing the same methodology. As shown in Table 1, reductive amina-
tion of aromatic aldehydes possessing nitro and cyano groups
proceeded to give the corresponding N-phenylamines in good
yields without reduction of the cyano or nitro groups (Table 1,
Financial support of this work from the Research Council of
Mazandaran University is gratefully acknowledged.
References and notes
1. Lane, C. F. Synthesis 1975, 135.
2. Abdel-Magid, A. F.; Carsone, K. G.; Harris, B. D.; Maryanoff, C. A.; Shah, R. D.
J. Org. Chem. 1996, 61, 3849.
3. (a) Bomann, M. D.; Guch, I. C.; Dimare, M. J. Org. Chem. 1995, 60, 5995; (b)
Pelter, A.; Rosser, R. M.; Mills, S. J. Chem. Soc., Perkin Trans. 1 1984, 717.
4. Ranu, B. C.; Majee, A.; Sarkar, A. J. Org. Chem. 1998, 63, 370.
5. Bhattacharyya, S. J. Org. Chem. 1995, 60, 4928.
6. Saxena, I.; Borah, R.; Sarma, J. C. J. Chem. Soc., Perkin Trans. 1 2000, 503.
7. Bhanushali, M. J.; Nandurkar, N. S.; Bhor, M.; Bhanag, B. M. Tetrahedron Lett.
2007, 48, 1273.
entries 2 and 3). In the case of
a,b-unsaturated aldehydes, such
as cinnamaldehyde, reductive amination was achieved success-
fully in excellent yield without reduction of the carbon–carbon
double bond (Table 1, entry 6). We found that both 4-bromo-
and 4-nitroaniline reacted efficiently with benzaldehyde in the
presence of ZBHNMP to produce the corresponding amines (Table
1, entries 7 and 8). However, in order to examine a greater range
of amines to better illustrate the scope and limitations of the
method, we investigated the reactions with aniline, N-methylan-
iline, benzylamine, morpholine, piperidine, pyrrolidine, and allyl-
amine using benzaldehyde as a representative aldehyde, and
cyclohexanone as a representative ketone (Table 1, entries 8–
20). Excellent yields of the expected amines were obtained.
Reductive amination of aliphatic ketones such as cyclohexanone
and heptan-2-one, and aldehydes such as butanal and hexanal
with aniline gave excellent yields of the corresponding amines
(Table 1, entries 21–23).
8. Alinezhad, H.; Ardestani, E. Lett. Org. Chem. 2007, 4, 473.
9. Bhattacharyya, S. Synth. Commun. 1997, 4265.
10. Heydari, A.; Arefi, A.; Esfandyari, M. J. Mol. Catal. A 2007, 274, 169.
11. Alinezhad, H.; Tajbakhsh, M.; Zamani, R. Synlett 2006, 431.
12. Firouzabadi, H.; Iranpoor, N.; Alinezhad, H. Bull. Chem. Soc. Jpn. 2003, 76, 143.
13. Alinezhad, H.; Tajbakhsh, M.; Salehian, F. Synlett 2005, 170.
14. Takashi, I.; Kazuhiro, N.; Michiko, M.; Hyroyuki, I.; Ayako, K.; Akio, O.
Tetrahedron 2004, 60, 6649.
15. Alinezhad, H.; Tajbakhsh, M.; Salehian, F. Monatsh. Chem. 2005, 136, 2029.
16. Sato, S.; Sakamoto, T.; Miyazawa, E.; Kikugava, Y. Tetrahedron 2004, 60, 7899.
17. Typical procedure for the reductive amination of aldehydes and ketones with
ZBHNMP: To a stirred solution of aldehyde or ketone (1 mmol) and amine
(1 mmol) in 5 mL of methanol was added the reducing agent (1 mmol) under
neutral conditions (pH 7). The pH was adjusted by addition of a 10% aqueous
solution of HCl in MeOH. The mixture was stirred, and the progress of the
reaction was followed by TLC (eluent: n-hexane/EtOAc 4:1). After completion,
water (10 mL) was added and the reaction mixture was extracted with diethyl
ether (2 Â 20 mL). The combined organic layers were dried over anhydrous
MgSO4 and evaporated. The crude product was purified by silica gel column
chromatography with n-hexane/EtOAc as the eluent to afford the pure amine.
18. Tajbakhsh, M.; Lakouraj, M. M.; Mohanazadeh, F.; Ahmadinejhad, A. Synth.
Commun. 2003, 229.
N-Methylpyrrolidine zinc borohydride was prepared according
to the literature procedure.18 All the products are known com-
pounds, and were identified by comparison of their spectra and
physical data with those of authentic samples.
In conclusion, ZBHNMP is a stable and versatile bench-top
reducing agent which is prepared easily from commercially avail-
able starting materials. It is a white powder and unlike its parent
compound Zn(BH4)2, is thermally stable and can be stored for sev-
eral months without appreciable loss of its reducing ability.
ZBHNMP is a good substitute for Na[BH3CN] for reductive amina-
tion of carbonyl compounds. Moreover, the simple reaction proce-
dure, easy work-up, selectivity, high reaction rates and yields, and
lack of requirement of an inert atmosphere or neutral conditions
make this stabilized transition-metal tetrahydroborate a useful
addition to the category of reagents used for the reductive prepa-
ration of amines.
19. Abdel-Magid, A. F.; Maryanoff, C. F. Synlett 1990, 537.
20. Kim, S.; Oh, C. H.; Ko, J. S.; Ahn, K. H.; Kim, Y. J. J. Org. Chem. 1985, 50, 1927.
21. Cho, B. T.; Kang, S. K. Synlett 2004, 1484.
22. Varma, R. S.; Dahiya, R. Tetrahedron 1998, 54, 6293.
23. Pin, L.; Jiangqing, L.; Gonghang, L.; Xunjun, Z. Youji Huaxue 1986, 6, 447.
24. Gribble, G. W.; Nutaitis, C. F. Synthesis 1987, 709.
25. Cho, B. T.; Kang, S. K. Tetrahedron 2005, 61, 5725.
26. Hutchins, R. O.; Markowitz, M. J. Org. Chem. 1981, 46, 3574.
27. Pelter, A.; Rosser, R. M. J. Chem. Soc., Perkin Trans. 1 1984, 717.
28. Gasc, M. B.; Perie, J.; Lattes, A. Tetrahedron 1978, 34, 1943.
29. Abdel-Magid, A. F.; Maryanoff, C. A.;Carson, K. G. Tetrahedron Lett. 1990, 31, 5595.