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B. Movassagh, S. Shokri / Tetrahedron Letters 46 (2005) 6923–6925
Table 1. Conversion of aldehydes into nitriles catalyzed by KF/Al2O3
Entry
Aldehydes
Time (h)
Nitriles
Yields (%)a
1
2
3
4
5
6
7
8
3-Nitrobenzaldehyde
4-Methoxybenzaldehyde
4-Methylbenzaldehyde
2-Methoxybenzaldehyde
Benzaldehyde
1-Naphthaldehyde
3-Methylbenzaldehyde
3-Bromobenzaldehyde
Phenylacetaldehyde
Crotonaldehyde
3-Butenalb
4.5
7
7.5
9
5
6
8
7
10.5
9
10
8
3-Nitrobenzonitrile
4-Methoxybenzonitrile
4-Methylbenzonitrile
2-Methoxybenzonitrile
Benzonitrile
1-Cyanonaphthalene
3-Methylbenzonitrile
3-Bromobenzonitrile
Benzylcyanide
trans-Crotononitrile
Allyl cyanide
Valeronitrile
Hexanenitrile
Decanonitrile
89
91
83
87
77
73
79
90
82
78
79
76
74
78
9
10
11
12
13
14
Valeraldehyde
Hexanal
Decanal
7.5
8.5
a Yields of isolated pure products.
b This compound was prepared by controlled hydrolysis of its dimethyl acetal, itself obtained by reaction of allylmagnesium chloride with
trimethylorthoformate;17 1H NMR (300 MHz, CDCl3): d 9.65 (1H, t, J = 1 Hz), 6.05–5.80 (1H, m), 5.36–5.18 (2H, m), 3.22–3.17 (2H, m).
The reaction between an aldehyde and hydroxylamine
hydrochloride produces first the corresponding aldox-
ime, which is then converted into the nitrile by dehydra-
tion. This heterogeneous system offers an easy work-up
that includes evaporation of DMF, addition of a suit-
able solvent to the residue, filtration to remove the solid
material, washing with water and evaporation of the
solvent.
Acknowledgment
We thank the K. N. Toosi University of Technology
Research Council and Kermanshah Oil Refining Com-
pany for financial support.
References and notes
1. Fabiani, M. E. Drug News Perspect. 1999, 12, 207–
216.
2. Chichiro, M.; Nagamoto, H.; Takemura, I.; Kitano, K.;
Komatsu, H.; Sekiguchi, K.; Tabusa, F.; Mori, T.;
Tominnaga, M.; Yabuuchi, Y. J. Med. Chem. 1995, 38,
353–358.
In summary, a new reliable, economical and practical
method for the synthesis of nitriles from the correspond-
ing aldehydes has been developed that features a simple
reaction procedure, easy work-up, ready availability of
the reagent and high yields of the products.
3. Judkins, B. D.; Allen, D. G.; Cook, T. A.; Evans, B.;
Sardharwala, T. E., Synth. Commun. 1996, 26, 4351–
4367.
4. Diana, G. D.; Catcliffe, D.; Volkots, D. L.; Mallamo, J. P.;
Bailey, T. R.; Vescio, N.; Oglesby, R. C.; Nitz, T. J.;
Wetzel, J.; Giranda, V.; Pevear, D. C.; Dutko, F. J.
J. Med. Chem. 1993, 36, 3240–3250.
5. Medwid, J. B.; Paul, R.; Baker, J. S.; Brockman, J. A.; Du,
M. T.; Hallett, W. A.; Hanifin, J. W.; Hardy, R. A.;
Tarrant, M. E.; Torley, I. W.; Wrenn, S. J. Med. Chem.
1990, 33, 1230–1241.
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F. J.; Callins, P. W.; Kobaldt, C. M.; Veenhuizen, A. W.;
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Y.; Gregory, S. A.; Seibert, K.; Isakson, P. C. J. Med.
Chem. 1997, 40, 1634–1647.
7. (a) Movassagh, B.; Shokri, S. Synth. Commun. 2005, 35,
887–890; (b) Yang, S. H.; Chang, S. Org. Lett. 2001, 3,
4209–4211; (c) Thomas, H. G.; Greyn, H. D. Synthesis
1990, 129–130; (d) Desai, D. G.; Swami, S. S.; Mahale, G.
D. Synth. Commun. 2000, 30, 1623–1625.
8. (a) Streith, J.; Fizet, C. Helv. Chim. Acta 1976, 59, 2786–
2792; (b) Miller, M. J.; Loudon, G. M. J. Org. Chem.
1975, 40, 126–127.
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1782.
Conversion of aldehydes into nitriles; general procedure:
A solution of hydroxylamine hydrochloride (1.1 mmol)
and aldehyde (1 mmol) in anhydrous DMF (10 mL)
was heated at 100 ꢁC. To this mixture was added with
stirring, over a period of 15 min, KF/Al2O3 (7.25 g,
40% by weight)7a and heating was continued for the
appropriate time (Table 1). After completion of the
reaction, DMF was removed in vacuo, dichloromethane
(20 mL) was added and the mixture filtered; the filtrate
was washed with water (2 · 10 mL) and dried over anhy-
drous sodium sulfate. The solvent was evaporated to
give the crude nitrile, which was purified by preparative
thin layer chromatography (silica gel, eluent n-hexane/
EtOAc = 7:3).
Allyl cyanide: Bp115–117 ꢁC (lit.15 bp116–121 ꢁC); IR
(neat): m 2220, 1636, 1408, 983, 924 cmÀ1 1H NMR
;
(300 MHz, CDCl3): d 5.82–5.69 (1H, m), 5.50–5.43
(1H, m), 5.35–5.30 (1H, m), 3.14 (2H, dt, J = 6.7,
1.7 Hz); 13C NMR (75 MHz, CDCl3):
119.48, 117.15, 21.37.
d 125.94,
4-Methoxybenzonitrile: Mp 59 ꢁC (lit.16 mp57–59 ꢁC);
IR (KBr): m 2150, 1596, 1498, 1255, 1177, 823 cmÀ1
;
1H NMR (300 MHz, CDCl3):
d
7.61 (2H, d,
11. (a) Das, B.; Ramesh, C.; Madhusudhan, P. Synlett 2000,
1599–1600; (b) Wang, E.-C.; Lin, G.-J. Tetrahedron Lett.
1998, 39, 4047–4050; (c) Lai, G.; Bhamare, N. K.;
Anderson, W. K. Synlett 2001, 230–231; (d) Bose, D. S.;
J = 8.5 Hz), 6.96 (2H, d, J = 8.5 Hz), 3.88 (3H, s); 13C
NMR (75 MHz, CDCl3): d 162.85, 133.94, 119.27,
114.76, 103.78, 55.56.