7408
S. K. De, R. A. Gibbs / Tetrahedron Letters 45 (2004) 7407–7408
NHR
1
4. (a) Mai, K.; Patil, G. Tetrahedron Lett. 1984, 125, 4583; (b)
Harusawa, S.; Hamada, Y.; Shiori, T. Tetrahedron Lett.
1979, 20, 4663; (c) Iyer, M. S.; Gigstad, M.; Namdev, N.
D.; Lipton, M. J. Am. Chem. Soc. 1996, 118, 4910; (d)
Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998,
120, 5315; (e) Takamura, M.; Hamashima, Y.; Usuda, H.;
Kanai, M.; Shibasaki, M. Angew. Chem., Int. Ed. Engl.
2000, 39, 1650; (f) Kobayashi, S.; Busujima, T.; Nagayama,
S. J. Chem. Soc., Chem. Commun. 1998, 981.
BiCl3
R-CHO + R -NH + TMSCN
1
2
CH CN, rt
3
R
CN
Scheme 1.
procedure that does not require a separate step to pre-
pare an imine for subsequent use. The significant fea-
tures of this method include (a) operational simplicity,
5
. Leonard, N. M.; Wieland, L. C.; Mohan, R. S. Tetrahedron
002, 58, 8373.
. Typical procedure: a mixture of benzaldehyde (106mg,
mmol), benzyl amine (110mg, 1mmol), and trimethylsilyl
cyanide (148mg, 1.5mmol) in acetonitrile (2mL) in the
presence of BiCl (32mg, 0.1mmol) was stirred at room
2
(
b) inexpensive reagents, (c) no need for any additive
6
to promote the reaction, (d) high yields of products,
and (e) the use of relatively non-toxic reagents and
solvents.
1
3
temperature. After completion of the reaction (TLC), the
reaction mixture was partitioned between 100mL of ether
and 50mL of water. The organic layer was washed with
Acknowledgements
4
brine (50mL), dried (MgSO ), and concentrated. The
Authors are thankful to reviewers for valuable
suggestions.
residue was chromatographed over silica gel (15% ethyl
acetate in hexane) to give a pure product.
. Selected spectral data: 2-(N-benzylamino)-2-phenylaceto-
7
1
References and notes
nitrile: H NMR (300MHz, CDCl ): d 1.85 (br s, NH), 3.96
3
(AB, q, J = 13.5Hz, 2H), 4.72 (s, 1H), 6.77 (d, J = 8Hz,
1H), 7.16 (t, J = 7.8Hz, 1H), 7.22–7.43 (m, 6H), 7.48–7.52
1
2
. Strecker, A. Ann. Chem. Pharm. 1850, 75, 27.
. Shafran, Y. M.; Bakulev, V. A.; Mokrushin, V. S. Russ.
Chem. Rev. 1989, 58, 148.
+
(m, 2H); MS m/z 223 (M + H) ; 2-(N-morpholino)-
1
2-phenylacetonitrile:
2.56–2.64 (m, 4H), 4.75–4.83 (m, 4H), 7.35–7.56 (m,
3
H NMR (300MHz, CDCl ): d
3
. (a) Weinstock, L. M.; Davis, P.; Handelsman, B.; Tull, R.
J. Org. Chem. 1967, 32, 2823; (b) Matier, W. L.; Owens, D.
A.; Comer, W. T.; Deitchman, D.; Ferguson, H. C.;
Seidehamel, R. J.; Young, J. R. J. Med. Chem. 1973, 16,
1
5H); 2-(N-benzylamino)-2-furfurylacetonitrile: H NMR
3
(300MHz, CDCl ): d 1.94 (br s, NH), 3.94 (AB, q,
J = 13.1Hz, 2H), 4.73 (s, 1H), 6.31 (m, 1H), 7.17–7.49 (m,
7H), MS m/z 213 (M + H) .
+
901.