RSC Advances
Page 6 of 7
DOI: 10.1039/C5RA07208E
2.65–2.63 (m, 1H), 2.20 (s, 3H), 1.75–1.68 (m, 4H); 13C NMR 55 311.0920.
(CDCl3, 75 MHz) δ 145.3, 130.0 (2C), 129.0, 115.0 (2C), 67.6
(2C), 59.3, 57.2, 37.2, 29.1 (2C).
Tris-(4-aminobenzyl)-amine (2r).15f Yellow gum, 98% yield.
1H NMR (CDCl3, 300 MHz) δ 7.12 (d, 6H, J = 8.25 Hz), 6.66 (d,
6H, J = 8.25 Hz), 3.66 (s, 6H), 3.60 (s, 6H); 13C NMR (CDCl3, 75
MHz) δ 145.1 (3C), 130.4 (3C), 129.2 (6C), 115.0 (6C), 52.5
4-(Pyrrolidin-1-yl)methyl aniline (2k). Yellowish oil, 99%
1
5
yield. IR (KBr) v 3372, 2929, 1623, 1582, 1382, 1288 cmꢀ1; H
NMR (CDCl3, 400 MHz) δ 7.11 (d, 2H, J = 8.24 Hz), 6.64 (d, 60 (3C).
2H, J = 8.24 Hz), 3.60 (s, 2H), 3.50 (s, 2H), 2.49–2.46 (m, 4H),
1.78–1.75 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 145.2, 130.1
Acknowledgements
(2C), 129.3, 114.9 (2C), 60.1, 53.9 (2C), 23.3 (2C); HRMS (ESIꢀ
This work was supported by NNSF of China (Nos. 21221062,
21372142 and 21472107).
10 TOF) (m/z): calcd for C11H16N2, [M+H]+ 177.1386; found
177.1388.
4-(Piperidin-1-yl)methyl aniline (2l).5d Yellowish oil, 98%
yield. H NMR (CDCl3, 400 MHz) δ 7.09 (d, 2H, J = 8.28 Hz),
6.63 (d, 2H, J = 8.24 Hz), 3.60 (s, 2H), 3.38 (s, 2H), 2.42–2.30
15 (m, 4H), 1.61–1.52 (m, 4H), 1.42–1.38 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ 145.2, 130.4 (2C), 128.1, 114.8 (2C), 63.3,
54.2 (2C), 25.9 (2C), 24.4.
Notes and references
1
65 a Department of Chemistry, Tsinghua University, Beijing 100084, P. R.
China. Fax: +86ꢀ10ꢀ62771149; Tel: +86ꢀ10ꢀ62795380; Eꢀmail:
† Electronic Supplementary Information (ESI) available: 1H and 13C
70 NMR spectra for products 2aꢀ2r. See DOI: 10.1039/b000000x/
4-(Morpholin-1-yl)methyl aniline (2m). Yellowish solid, mp
100–102 oC (lit.15d mp 100–102 oC), 97% yield. 1H NMR (CDCl3,
20 300 MHz) δ 7.10 (d, 2H, J = 8.24 Hz), 6.64 (d, 2H, J = 8.25 Hz),
3.70–3.67 (m, 4H), 3.62 (s, 2H), 3.37 (s, 2H), 2.42–2.39 (m, 4H);
13C NMR (CDCl3, 75 MHz) δ 145.4, 130.3 (2C), 127.5, 114.9
(2C), 67.0 (2C), 63.0, 53.5 (2C).
1
2
3
(a) S. Nishimura, Handbook of heterogeneous catalytic
hydrogenation for organic synthesis, John Wiley & Sons, Inc., New
York, 2001, Chapter 9; (b) P. N. Rylander, Hydrogenation methods,
Academic Press, London, 1985, Chapter 8.
75
(a) S. Nishimura, Handbook of heterogeneous catalytic
hydrogenation for organic synthesis, John Wiley & Sons, Inc., New
York, 2001, Chapter 13; (b) P. N. Rylander, Hydrogenation methods,
Academic Press, London, 1985, Chapter 13.
4-(N-Methyl-N-phenyl-aminomethyl)
aniline
(2n).15e
1
In general, the order of ease of hydrogenolysis of benzylamines is
tertiary > secondary > primary. N,NꢀDisubstituted benzylamine
smoothly underwent a hydrogenolysis over PdꢀC catalyst, while
benzylamine and Nꢀmonosubstituted benzylamine usually stayed
intact. Therefore, only N,Nꢀdisubstituted benzylamines were suitable
to be used as protective groups, see: T. W. Greene and P. G. M.
Wuts, Protective Groups in Organic Synthesis, 3rd edn., John Wiley
& Sons, Inc., New York, 1999.
25 Yellowish oil, 99% yield. H NMR (CDCl3, 300 MHz) δ 7.21–
7.19 (m, 2H), 6.75–6.58 (m, 7H), 4.38 (s, 2H), 3.55 (s, 2H), 2.93
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 149.9, 145.1, 129.0 (2C),
128.6, 127.9 (2C), 116.3, 115.2 (2C), 112.4 (2C), 56.0, 38.1.
80
85
N-[4-(N-Ethyl-N-phenyl-aminomethyl)phenyl] acetamide
30 (2o). Yellowish oil, 88% yield. IR (KBr) v 3285, 3185, 2967,
1658, 1598, 1505, 1408, 1248 cmꢀ1; 1H NMR (CDCl3, 300 MHz)
δ 7.42–7.14 (m, 7H), 6.69–6.63 (m, 3H), 4.46 (s, 2H), 3.44 (q,
2H, J = 6.87 Hz), 2.14 (s, 3H), 1.18 (t, 3H, J = 6.87 Hz); 13C
NMR (CDCl3, 75 MHz) δ 168.4, 148.3, 136.5, 135.1, 129.1 (2C),
35 127.0 (2C), 120.2 (2C), 116.0, 112.1 (2C), 53.4, 45.0, 24.3, 12.0;
HRMS (ESIꢀTOF) (m/z): calcd for C17H20N2O, [M+Na]+:
291.1468; found 291.1463.
4
5
M. Baba, O. Nishimura, N. Kanzaki, M. Okamoto, H. Sawada, Y.
Iizawa, M. Shiraishi, Y. Aramaki, K. Okonogi, Y. Ogawa, K.
Meguro and M. Fujino, Proc. Natl. Acad. Sci. USA, 1999, 96, 5698–
5703.
90
Selected references for dissolving metal reductions: (a) X. Liang, H.
Pei, L. Ma, Y. Ran, J. Chen, G. Wang and L. Chen, Molecules, 2014,
19, 6163–6183; (b) H.ꢀJ. Kim, M. I. ElꢀGamal, Y. S. Lee and C.ꢀH.
Oh, Bull. Korean Chem. Soc., 2013, 34, 2480–2486; (c) H. Konno, S.
Aimoto, S. O. Smith, K. Nosaka and K. Akaji, Bioorg. Med. Chem.,
2009, 17, 5769–5774; (d) H.ꢀR. Tsou, M. Otteng, T. Tran, M. B.
Floyd, Jr., M. Reich, G. Birnberg, K. Kutterer, S. AyralꢀKaloustian,
M. Ravi, R. Nilakantan, M. Grillo, J. P. McGinnis and S. K.
Rabindran, J. Med. Chem., 2008, 51, 3507–3525; (e) B. Lagu, C.
Gerchak, M. Pan, C. Hou, M. Singer, R. Malaviya, M. Matheis, G.
Olini, D. Cavender and M. Wachter, Bioorg. Med. Chem. Lett., 2007,
17, 4382–4386; (f) H. Hashimoto, T. Ikemoto, T. Itoh, H. Maruyama,
T. Hanaoka, M. Wakimasu, H. Mitsudera and K. Tomimatsu, Org.
Proc. Res. Dev., 2002, 6, 70–73; (g) G. Ronsisvalle, O. Prezzavento,
A. Marrazzo, F. Vittorio, M. Massimino, G. Murari and S.
Spampinato, J. Med. Chem., 2002, 45, 2662–2665; (h) M. Mitsuya, K.
Kobayashi, K. Kawakami, A. Satoh, Y. Ogino, T. Kakikawa, N.
Ohtake, T. Kimura, H. Hirose, A. Sato, T. Numazawa, T. Hasegawa,
K. Noguchi and T. Mase, J. Med. Chem., 2000, 43, 5017–5029.
95
100
105
N-[4-(N-Butyl-N-phenyl-aminomethyl)phenyl] acetamide
(2p). Yellowish oil, 85% yield. IR (KBr) v 3286, 2952, 2867,
40 1659, 1599, 1505, 1408, 1317 cmꢀ1; 1H NMR (CDCl3, 400 MHz)
δ 7.25–7.13 (m, 7H), 6.67–6.63 (m, 2H), 4.48 (s, 2H), 3.33–3.38
(m, 2H), 2.15 (s, 3H), 1.62–1.60 (m, 2H), 1.35–1.33 (m, 2H),
0.94 (t, 3H, J = 9.64 Hz); 13C NMR (CDCl3, 75 MHz) δ 168.3,
148.5, 136.4, 135.1, 129.1 (2C), 127.0 (2C), 120.2 (2C), 115.9,
45 112.1 (2C), 54.0, 51.0, 29.2, 24.4, 20.3, 13.9; HRMS (ESIꢀTOF)
(m/z): calcd for C19H24N2O, [M+Na]+ 319.1781; found 319.1779.
N-[2-[N-Methyl-N-(2-chlorophenyl)-aminomethyl]phenyl]
acetamide (2q). Yellowish oil, 88% yield. IR (KBr) v 3260,
1
2854, 2803, 1686, 1516, 1443, 1304 cmꢀ1; H NMR (CDCl3, 300
110
115
6
Selected references for catalytic transfer hydrogenation: (a) J. Ma, D.
Chen, K. Lu, L. Wang, X. Han, Y. Zhao and P. Gong, Eur. J. Med.
Chem., 2014, 86, 257–269; (b) Y. Lu, T. Ran, G. Lin, Q. Jin, J. Jin,
H. Li, H. Guo, T. Lu and Y. Wang, Chem. Pharm. Bull., 2014, 62,
238–246; (c) M. Koufaki, C. Kiziridi, P. Papazafiri, A.
Vassilopoulos, A. Varro, Z. Nagy, A. Farkas and A. Makriyannis,
Bioorg. Med. Chem., 2006, 14, 6666–6678.
50 MHz) δ 9.82 (s, 1H), 8.22–8.19 (m, 1H), 7.40–7.02 (m, 7H), 4.17
(s, 2H), 2.62 (s, 3H), 2.16 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ
168.6, 148.4, 138.3, 130.5, 130.2, 129.5, 128.6, 127.8, 125.3,
125.2, 123.4, 121.9, 121.6, 58.8, 41.9, 24.7; HRMS (ESIꢀTOF)
(m/z): calcd for C16H17ClN2O, [M+Na]+ 311.0922; found
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