Communication
RSC Advances
monoalkylated amines. The yield of N-benzylaniline was greatly Professional Development Project: Under the Science Achieve-
improved from 53% to 87% with prolonged reductive amination ment Scholarship of Thailand (SAST) are gratefully acknowl-
step (entry 6). Under similar condition, N-benzyl-4-methoxya- edged for nancial support.
niline was also obtained in good yield (88%, entry 7). However,
due to the strong electron withdrawing effect of the nitro group,
the least reactive 4-nitroaniline gave the desired amine in only
Notes and references
5
5% yield along with 40% of benzyl alcohol by-product (entry 8).
Slightly better results were obtained with the more reactive
1 R. N. Salvatore, C. H. Yoon and K. W. Jung, Tetrahedron,
2001, 57, 7785–7811.
benzyl bromide. Since benzyl bromide is a good substrate for
NMO oxidation, addition of KI catalyst is not necessary. The
reactions of benzyl bromide with a series of amines proceeded
smoothly to afford high yields of the corresponding amines
2 T. Naito, Chem. Pharm. Bull., 2008, 56, 1367–1383.
3 J. F. Hartwig, Acc. Chem. Res., 2008, 41, 1534–1544.
4 B. M. Trost and I. Fleming, Comprehensive Organic Synthesis,
Pergamon Press, 1991.
(
entries 9–12).
5 (a) C. Chiappe and D. Pieraccini, Green Chem., 2003, 5, 193–
197; (b) Y. Ju and R. S. Varma, Green Chem., 2004, 6, 219–221;
(c) G. Cami-Kobeci, P. A. Slatford, M. K. Whittlesey and
J. M. J. Williams, Bioorg. Med. Chem. Lett., 2005, 15, 535–
537; (d) C. Chiappe, P. Piccioli and D. Pieraccini, Green
Chem., 2006, 8, 277–281; (e) F. M. Moghaddam,
S. M. DokhtTaimoory, H. Ismaili and G. R. Bardajee, Synth.
Commun., 2006, 36, 3599–3607; (f) M. B. Gawande,
S. S. Deshpande, J. R. Satam and R. V. Jayaram, Catal.
Commun., 2007, 8, 576–582; (g) C. B. Singh, V. Kavala,
A. K. Samal and B. K. Patel, Eur. J. Org. Chem., 2007, 1369–
1377; (h) B. Basu, S. Paul and A. K. Nanda, Green Chem.,
2009, 11, 1115–1120; (i) A.-S. Delepine, R. Tripier,
H. Bernard, N. Le Bris and H. Handel, Tetrahedron Lett.,
2009, 50, 2521–2524; (j) J. W. Kim, K. Yamaguchi and
N. Mizuno, J. Catal., 2009, 263, 205–208; (k) G. Marzaro,
A. Guiotto and A. Chilin, Green Chem., 2009, 11, 774–776;
(l) T. Ruether, T. Ross, E. J. Mensforth and
A. F. Hollenkamp, Green Chem., 2009, 11, 804–809; (m)
P. Linciano, M. Pizzetti, A. Porcheddu and M. Taddei,
Synlett, 2013, 2249–2254.
12
In agreement with our previous study, the rate of benzyl
halide oxidation was depended on electronic nature of the
substituents on aromatic ring. Substrates with electron-
donating groups were more reactive than those containing
electron-withdrawing groups. Benzyl chlorides with electron
donating groups such as –OCH3 and –CH3 were converted
readily to the corresponding aldehydes leading to relatively high
yields of the amine products (entries 13–22). However, the
oxidation of 4-nitrobenzyl chloride was rather sluggish and only
7
7% yield of the desired amine was obtained even with pro-
longed oxidation step (entry 23).
It is noted that although this sequence reaction can be per-
formed with other less reactive primary aliphatic halides, the
reaction rate for the oxidation step is much slower and generally
requires a longer time for completion of the reaction. In fact,
9
1% yield of N-benzyldecan-1-amine was isolated based on 54%
conversion of dodecyl bromide aer subjected to 60 min
oxidation. Nevertheless, attempts to perform the reaction with
secondary halides such as cyclohexyl bromide and 3-bromocy-
clohexene failed to give satisfactory results due to competitive
elimination during NMO oxidation.
In summary, for the rst time, a one-pot procedure for
conversion of benzyl halides into amines via a sequential
oxidation/reductive amination under solventless ultrasonic
irradiation was reported. This protocol provided several bene-
6 R. P. Tripathi, S. S. Verma, J. Pandey and V. K. Tiwari, Curr.
Org. Chem., 2008, 12, 1093–1115.
7 (a) R. F. Borch, Org. Synth., 1988, 6, 499; (b) A. F. Abdel-
Magid, K. G. Carson, B. D. Harris, C. A. Maryanoff and
R. D. Shah, J. Org. Chem., 1996, 61, 3849–3862; (c)
A. V. Panlov, Y. D. Markovich, A. A. Zhirov, I. P. Ivashev,
A. T. Kirsanov and V. B. Kondrat'ev, Pharm. Chem. J., 2004,
34, 371–373; (d) A. F. Abdel-Magid and S. J. Mehrman, Org.
Process Res. Dev., 2006, 10, 971–1031; (e) K. Nagaiah,
V. N. Kumar, R. S. Rao, B. V. S. Reddy, A. V. Narsaiah and
J. S. Yadav, Synth. Commun., 2006, 36, 3345–3352; (f)
P. S. Reddy, S. Kanjilal, S. Sunitha and R. B. N. Prasad,
Tetrahedron Lett., 2007, 48, 8807–8810; (g) H. Alinezhad,
M. Tajbakhsh, F. Salehian and K. Fazli, Tetrahedron Lett.,
2009, 50, 659–661; (h) E. E. Boros, J. B. Thompson,
S. R. Katamreddy and A. J. Carpenter, J. Org. Chem., 2009,
74, 3587–3590; (i) C. L. Devi, O. S. Olusegun,
C. N. S. S. P. Kumar, V. J. Rao and S. Palaniappan, Catal.
Lett., 2009, 132, 480–486; (j) P. N. Grenga, B. L. Sumbler,
F. Beland and R. Priefer, Tetrahedron Lett., 2009, 50, 6658–
ts over the conventional mode including simple equipment
set-up, used no solvent, and easy work-up. In addition, the mild
oxidation with NMO is compatible with the subsequence
reduction step, thus allows a clean synthesis of amine from the
two step oxidation–reduction conducted in one pot. In most
cases, primary benzylic halides together with a range of amines
could be efficiently converted into secondary and tertiary
amines in good to excellent yields without detectable side
products from overalkylation or aldehyde reduction. Moreover,
the crude mixture can be puried simply by applied directly
onto a chromatography column. The reaction is simple, rapid
and eco-friendly which could be potentially useful alternative
for selective synthesis of N-alkylated amines.
Acknowledgements
6660; (k) J. Deng, L.-P. Mo, F.-Y. Zhao, L.-L. Hou, L. Yang
The Center of Excellence for Innovation in Chemistry (PERCH-
CIC), the National Research University Project under Thailand's
Office of the Higher Education Commission, and the Research
and Z.-H. Zhang, Green Chem., 2011, 13, 2576–2584; (l)
A. Shokrolahi, A. Zali and M. H. Keshavarz, Green Chem.
Lett. Rev., 2011, 4, 195–203.
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