LETTER
N-Arylputrescines and Cadaverines
753
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J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144.
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(9) Salvatore, R. N.; Yoon, Ch. H.; Jung, K. W. Tetrahedron
2001, 57, 7785.
Table 3 Reduction of Compounds 2
BH3, THF
NH2
( )n
( )n
CN
ArHN
ArHN
2
1
Compd 1
1a
n
1
1
1
1
1
1
1
1
2
2
2
2
Ar
Yield (%)a
Ph
80
83
82
79
78
72
81
79
82
75
81
79
(10) Romera, J. L.; Cid, J. M.; Trabanco, A. A. Tetrahedron Lett.
1b
1c
4-BrC6H4
4-FC6H4
2004, 45, 8797.
(11) (a) Salvatore, R. N.; Nagle, A. S.; Schmidt, S. E.; Jung,
K. W. Org. Lett. 1999, 1, 1893. (b) Salvatore, R. N.;
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E. A.; Sahab, S.; Yoon, C. H.; Jung, K. W. Tetrahedron Lett.
2003, 44, 5695. (e) Cohen, R. J.; Fox, D. L.; Eubank, J. F.;
Salvatore, R. N. Tetrahedron Lett. 2003, 8617. (f) Cui, S.-
L.; Jiang, Z.-Y.; Wang, Y.-G. Synlett 2004, 1829. (g) Fink,
D. M. Synlett 2004, 13, 2394. (h) Lehman, F. Synlett 2004,
2447. (i) Varala, R.; Ramu, M. M. A.; Adapa, S. R. Synlett
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367. (m) Kondoh, A.; Yorimitsu, H.; Oshima, K.
Tetrahedron 2006, 62, 2357. (n) Bhowruth, V.; Brown,
A. K.; Senior, S. J.; Snaith, J. S.; Besra, G. S. Bioorg. Med.
Chem. Lett. 2007, 17, 5643. (o) Bisoyi, H. K.; Kumar, S.
Tetrahedron Lett. 2007, 48, 4399.
1d
1e
4-MeC6H4
2-MeC6H4
1-C10H7
1f
1g
4-MeOC6H4
3,4-(MeO)2C6H3
Ph
1h
1i
1j
2-MeC6H4
4-MeOC6H4
3,4-(MeO)2C6H3
1k
1l
a Yields correspond to pure compounds.
(12) Kruizinga, W. H.; Kellog, R. M. J. Am. Chem. Soc. 1981,
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(13) Galli, C. Org. Prep. Proced. Int. 1992, 24, 285.
(14) Representative Procedure for the Synthesis of
Compounds 2
References and Notes
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Clinical Approaches; Landes Bioscience Publishers: Austin,
TX, 1996.
A solution of 4-chlorobutyronitrile (2.5 mmol) in DMF
(1 mL) was added during 1.5 h to a mixture of aniline (2.5
mmol), Cs2CO3 (2.5 mmol), and KI (5 mmol) in DMF
(4 mL). The mixture was stirred 2.5 h at 95 °C. After
completion of the reaction, as indicated by TLC, the mixture
was treated with Et2O (50 mL) and H2O (10 mL). The
aqueous phase was separated and extracted with Et2O (30
mL). The combined organic layers were dried over anhyd
Na2SO4 and filtered. The solvent was evaporated in vacuo.
The crude product was purified by column chromatography
(SiO2, hexane–CHCl3) to furnish 4-(phenylamino)butyro-
nitrile in 69% yield as an oil.
Spectral and Analytical Data for Selected Compounds
4-(Phenylamino)butyronitrile (2a) was obtained as an oil
(69%). 1H NMR (300 MHz, CDCl3): d = 7.17–7.22 (2 H, m),
6.74 (1 H, dt, J = 7.4, 1.0 Hz), 6.61 (2 H, dd, J = 8.8, 1.0 Hz),
3.68 (1 H, br s), 3.33 (2 H, t, J = 6.7 Hz), 2.49 (2 H, t, J = 7.0
Hz), 1.93–2.02 (2 H, m). 13C NMR (75 MHz, CDCl3): d =
147.63, 129.43, 119.50, 117.91, 112.87, 42.31, 25.26, 14.81.
Anal. Calcd for C10H12N2: C, 74.97; H, 7.55; N, 17.48.
Found: C, 74.87; H, 7.65; N, 17.42.
(3) (a) Frydman, B.; Valasinas, A. Expert Opin. Ther. Pat. 1999,
9, 1055. (b) Aizencang, G.; Harari, P.; Buldain, G.; Guerra,
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3, 951. (g) Bergeron, R. J.; Yao, G. W.; Yao, H.; Weimar,
W. R.; Sninski, C. A.; Raisler, B.; Feng, Y.; Wu, Q.; Gao, F.
J. Med. Chem. 1996, 39, 2461.
(4) (a) Orelli, L. R.; García, M. B.; Perillo, I. A. Heterocycles
2000, 53, 2437. (b) García, M. B.; Grilli, S.; Lunazzi, L.;
Mazzanti, A.; Orelli, L. J. Org. Chem. 2001, 66, 6679.
(c) García, M. B.; Grilli, S.; Lunazzi, L.; Mazzanti, A.;
Orelli, L. Eur. J. Org. Chem. 2002, 4018. (d) García, M. B.;
Orelli, L. R.; Magri, M. L.; Perillo, I. A. Synthesis 2002,
2687. (e) Magri, M. L.; Vanthuyne, N.; Roussel, C.; García,
M. B.; Orelli, L. R. J. Chromatorgr., A 2005, 1069, 203.
(f) García, M. B.; Torres, R. A.; Orelli, L. R. Tetrahedron
Lett. 2006, 47, 4857.
N,N-Bis(3-cyanopropyl)aniline (3a) was obtained as an oil.
1H NMR (300 MHz, CDCl3): d = 7.24–7.27 (3 H, m), 6.80
(1 H, t, J = 7.3 Hz), 6.75 (2 H, d, J = 8.0 Hz), 3.44 (4 H, t,
J = 7.1 Hz), 2.38 (4 H, t, J = 7.0 Hz), 1.90–1.96 (4 H, m). 13
C
(5) Hedrera, M. E.; Perillo, I. A. J. Heterocycl. Chem. 2000, 37,
1431.
(6) Abd-El-Aziz, A.; Bernardin, S. A.; Tran, K. Tetrahedron
Lett. 1999, 40, 1835.
(7) Perillo, I. A.; Fernández, B. M.; Lamdan, S. J. Chem. Soc.,
Perkin Trans. 2 1977, 2068.
NMR (75 MHz, CDCl3): d = 147.08, 129.64, 119.28, 118.30,
114.10, 50.26, 23.09, 14.73. Anal. Calcd for C14H17N3: C,
73.98; H, 7.54; N, 18.49. Found: C, 73.84; H, 7.59; N, 18.51.
5-(Phenylamino)valeronitrile (2i) was obtained as an oil
(65%). 1H NMR (300 MHz, CDCl3): d = 7.18–7.21 (2 H, m),
Synlett 2009, No. 5, 751–754 © Thieme Stuttgart · New York