LETTER
Efficient Catalyst for the One-Pot Synthesis of a-Amino Nitriles
1769
Table 1 Heteropoly Acid Catalyzed Synthesis of a-Amino Nitriles with TMSCN
Entry
Aldehyde
Amine
Time (h)
Yield (%)
Mp (°C)
Found
72–73
Reported
1
2
3
4
5
6
7
8
9
Benzaldehyde
Aniline
3
97
94
96
95
96
95
93
91
92
94
95
73–748
109–1128
–
4-Chlorobenzaldehyde
3-Methoxybenzaldehyde
4-Methylbenzaldehyde
4-Methoxybenzaldehyde
Benzaldehyde
Aniline
5.5
5
108–112
Yellow oil
75–77
Benzylamine
Aniline
4.5
5
76–788
94–958
Oil12
Aniline
93–95
Benzylamine
Aniline
4.5
5
Oil
Cynamaldehyde
116–118
Yellow oil
125–127
Oil
117–1198
–
Isobutyraldehyde
Benzylamine
Aniline
5.15
4.5
4.5
5
Isobutyraldehyde
–
1
1
0
1
4-Chlorobenzaldehyde
4-Methylbenzaldehyde
Benzylamine
Benzylamine
Oil22
Oil
Oil22
The major advantage of this method is that it is truly a References
one-pot procedure that does not require a separate step to
prepare an imine for subsequent use.
(
(
1) Dyker, G. Angew. Chem., Int. Ed. Engl. 1997, 36, 1700.
2) (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, 901.
3) Mai, K.; Patil, G. Tetrahedron Lett. 1984, 25, 4583.
4) Groger, H. Chem. Rev. 2003, 103, 2795.
All products were identified by comparison of their physical and
7
,8,10–12
spectroscopic data with those of authentic samples.
(
(
(
Synthesis of a-Amino Nitriles – General Procedure
5) Iyer, M. S.; Gigstad, M.; Namdev, N. D.; Lipton, M. J. Am.
Chem. Soc. 1996, 118, 4910.
A mixture of an aldehyde (1 mmol), amine (1 mmol), TMSCN (1.2
mmol) and catalyst H P (0.02 g, 0.003 mmol) in MeCN (5 mL)
1
4 5
(
(
(
(
6) Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120,
was refluxed for the indicated time (Table 1) under vigorous stir-
ring. The progress of the reaction was monitored by TLC. After fil-
tration and washing of the catalyst with MeCN, the solvent was
removed under reduced pressure and the crude product was purified
5
315.
7) Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron 2002, 58,
529.
2
8) Yadav, J. S.; Subba Reddy, B. V.; Eeshwaraiah, B.; Srinivas,
M. Tetrahedron 2004, 60, 1767.
by column chromatography over silica gel (hexane–Et O) or recrys-
2
tallized from absolute EtOH to obtain the pure product (Scheme 1).
9) De, S. K.; Gibbs, R. A. Tetrahedron Lett. 2004, 45, 7407.
(
10) De, S. K. Synth. Commun. 2005, 35, 1577.
Spectral and Physical Data for Selected Compounds
(11) De, S. K. J. Mol. Catal. A: Chem. 2005, 225, 169.
2
-(N-Benzylamino)-2-(3-methoxyphenylacetonitrile (Entry 3)
1
(12) Yadav, J. S.; Reddy, B. V. S.; Eshwaraiah, B.; Srinivas, M.;
Vishnumurthy, P. New. J. Chem. 2003, 27, 462.
(13) Royer, L.; De, S. K.; Gibbs, R. A. Terahedron Lett. 2005, 46,
595.
(14) Heydari, A.; Fatemi, P.; Alizadeh, A. A. Tetrahedron Lett.
998, 39, 3049.
(
(
H NMR (300 MHz, CDCl ): d = 1.84 (br s, 1 H), 3.76 (s, 3 H), 3.95
3
(
AB, q, J = 13.0 Hz, 2 H), 4.65 (s, 1 H), 6.85 (dd, J = 2.4, 9 Hz, 1
1
3
H), 7.14–7.36 (m, 2 H), 7.28–7.43 (m, 6 H). C NMR (75 MHz,
4
CDCl ): d = 51.6, 53.9, 55.7, 113.4, 114.8, 119.2, 119.8, 128.5,
3
+
1
1
29.7, 128.8, 130.4, 136.7, 138.6, 160.4. MS (EI): m/z = 252 [M ],
22, 91, 77.
1
15) Strecker, A. Ann. Chem. Pharm. 1850, 75, 27.
16) Harusawa, S.; Hamada, Y.; Shioiri, T. Tetrahedron Lett.
1979, 20, 4663.
2
-(N-Benzylamino)-2-isopropylacetonitrile (Entry 8)
1
H NMR (300 MHz, CDCl ): d = 1.08 (d, J = 6.5 Hz, 3 H), 1.09 (d,
3
(
17) (a) Chakraborty, T. K.; Readdy, G. V.; Hussain, K. A.
Tetrahedron Lett. 1991, 32, 7597. (b) Leblanc, J. P.;
Gibson, H. W. Tetrahedron Lett. 1992, 33, 6295.
18) (a) Kozhevnikov, I. V. Chem. Rev. 1998, 98, 171.
(b) Kozhevnikov, I. V. Catal. Rev. Sci. Eng. 1995, 37, 311.
J = 6.5 Hz, 3 H), 1.56 (br s, 1 H), 1.97–2.02 (m, 1 H), 3.24 (d,
J = 6.0 Hz, 1 H), 3.80 (d, J = 13.0 Hz, 1 H), 4.07 (d, J = 13.0 Hz, 1
1
3
H), 7.24–7.43 (m, 5 H). C NMR (75 MHz, CDCl ): d = 18.2, 19.3,
3
(
3
1
1.3, 51.8, 56.3, 119.3, 127.5, 128.4,128.7, 138.4. MS (EI): m/z =
+
88 [M ].
(c) Okuhara, T.; Mizuno, N.; Misono, M. Adv. Catal. 1996,
41, 113.
2
-(N-Anilino)-2-isopropylacetonitrile (Entry 9)
–
1
IR (KBr): 3346, 2234 cm .
Synlett 2006, No. 11, 1768–1770 © Thieme Stuttgart · New York