PAPER
Synthesis of Nitriles
3183
only benzaldehyde oxime and benzonitrile, was collected into
CH2Cl2, dried (MgSO4) and concentrated under reduced pressure.
The parameters are given in Table 5.
Thiophene-3-carbonitrile
FVP of thiophene-3-carbaldoxime (318 mg, 2.5 mmol, 135 °C,
350 °C, 1 × 10–2 Torr, 15 min) over 3A MS using work-up Method
A yielded thiophene-3-carbonitrile after distillation as a clear oil
(209 mg, 77%); bp 210 °C/760 Torr (Lit.30 bp 203–205 °C/760
Torr).
Table 5 FVP of Benzaldoxime (3 R = Ph) over 3A MS (Inlet Tem-
perature 60 °C)
1H NMR: d = 9.02 (1 H, dd, J = 3.0, 1.2 Hz), 7.40 (1 H, dd, J = 5.1,
3.0 Hz), 7.27 (1 H, dd, J = 5.1, 1.2 Hz).
13C NMR: d = 135.22, 128.43, 127.12, 114.90 (Cq), 110.37 (Cq).
Quantity
(mg)
Furnace
temp (°C)
Pressure
(Torr)
Pyrolysis
time (min)
Conversion
127
97
300
350
400
450
0.01
0.01
0.01
0.01
10
10
10
10
>90
>90
>90
100
Acknowledgment
109
80
We are grateful to the EPSRC and to Zeneca plc for a CASE award
(G.M.) and to EPSRC and Chemistry Innovation Knowledge Trans-
fer Network for a post-doctoral fellowship (R.G.T.).
Dehydration of Oximes; Typical Procedures
Benzonitrile
References
FVP of benzaldoxime (97 mg, 8.0 mmol, 60 °C, 350 °C, 1 × 10–2
Torr, 10 min) over 3A MS using work-up Method B gave benzoni-
trile (80 mg, 97%); spectroscopic data as above.
(1) March, J. Advanced Organic Chemistry, 3rd ed.; Wiley-
Interscience: New York, 1985, 1169.
(2) For example: Li, D.; Shi, F.; Guo, S.; Deng, Y. Tetrahedron
Lett. 2005, 46, 671.
FVP of benzaldoxime (991 mg, 8.2 mmol, 95 °C, 200 °C, 7.0 × 10–2
Torr, 80 min) over WO3 using work-up Method C gave benzonitrile
as a clear liquid (781 mg, 92%); spectroscopic data as above.
(3) Reviews: (a) Hurd, C. D. The Pyrolysis of Carbon
Compounds; Chemical Catalog Company: New York, 1929,
582. (b) Hurd, C. D. The Pyrolysis of Carbon Compounds;
Chemical Catalog Company: New York, 1929, 659.
(4) For example: Lancaster, M. Green Chemistry; Royal Society
of Chemistry: Cambridge, 2002.
(5) (a) Billups, W. E.; McCord, D. J. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1332. (b) Denis, J.-M.; Gaumont, A.-C. In
Gas Phase Reactions in Organic Synthesis; Vallée, Y., Ed.;
Gordon and Breach: Amsterdam, 1997.
2-Cyanophenol
FVP of salicylaldoxime (808 mg, 5.9 mmol, 180 °C, 350 °C, 5 × 10–3
Torr, 30 min) over 3A MS using work-up Method B provided a yel-
low solid which, after distillation, was identified as 2-cyanophenol
(621 mg, 88%); mp 90–93 °C (Lit.19 mp 97–98 °C); spectroscopic
data as above.
FVP of salicylaldoxime (1001 mg, 7.3 mmol, 145 °C, 400 °C,
3.0 × 10–2 Torr, 36 min) over WO3 using work-up Method A gave
2-cyanophenol as a dark yellow solid (758 mg, 87%); mp 93–95 °C
(Lit.19 mp 97–98 °C); spectroscopic data as above.
(6) Hodgetts, I.; Noyce, S. J.; Storr, R. C. Tetrahedron Lett.
1984, 25, 5435.
(7) Bader, H.; Hopf, H.; Jäger, H. Chem. Ber. 1989, 122, 1193.
(8) (a) Laporterie, A.; Dubac, J.; Mazerolles, P.; Iloughmane, H.
J. Organomet. Chem. 1981, 216, 321. (b) Laporterie, A.;
Manuel, G.; Dubac, J.; Mazerolles, P.; Iloughmane, H. J.
Organomet. Chem. 1981, 210, C33.
(9) Van der Waals, A. C. L. M.; Klunder, A. J. H.; van Buren, F.
R.; Zwanenburg, B. J. Mol. Catal. A: Chem. 1998, 134, 179.
(10) Sen, S. E.; Smith, S. M.; Sullivan, K. A. Tetrahedron 1999,
55, 12657.
(11) Barton, D. G.; Soled, S. L.; Iglesia, E. Top. Catal. 1998, 6,
87.
(12) McDougald, G. PhD Thesis; The University of Edinburgh:
UK, 2000.
Pyrrole-2-carbonitrile
FVP of pyrrole-2-carbaldoxime (870 mg, 7.9 mmol, 150 °C,
350 °C, 1 × 10–3 Torr, 120 min) over 3A MS using work-up Method
B gave pyrrole-2-carbonitrile (457 mg, 63%) as an orange oil; bp
80 °C/0.3 Torr (Lit.28 bp 89–90 °C/1.5 Torr).
1H NMR: d = 9.65 (1 H, br s), 6.86 (1 H, dd, J = 2.7, 1.4 Hz), 6.79
(1 H, dd, J = 3.8, 1.4 Hz), 6.17 (1 H, dd, J = 3.8, 2.7 Hz).
13C NMR: d = 123.78, 120.11, 114.77 (Cq), 109.84 and 100.28 (Cq).
FVP of pyrrole-2-carbaldoxime (971 mg, 8.8 mmol, 170 °C,
400 °C, 2.5 × 10–2 Torr, 30 min) over WO3 using work-up Method
B gave pyrrole-2-carbonitrile as a dark yellow liquid (732 mg,
90%); bp 38–43 °C/0.05 Torr (Lit.28 bp 89–90 °C/1.5 Torr); spec-
troscopic data as above.
(13) Duffy, E. F.; Foot, J. S.; McNab, H.; Milligan, A. A. Org.
Biomol. Chem. 2004, 2, 2677.
(14) Dunlop, A. P.; Peters, F. N. The Furans; American Chemical
Society: New York, 1953, 544.
(15) Krause, J. G.; Shaikh, S. Synthesis 1975, 502.
(16) Pakrashi, S. C. J. Org. Chem. 1971, 36, 642.
(17) Kazmirowski, H. G.; Landmann, H.; Walsmann, P.
Pharmazie 1969, 24, 378.
(18) Xiang, Y.-B.; Drenkard, S.; Baumann, K.; Hickey, D.;
Eschenmoser, A. Helv. Chim. Acta 1994, 77, 2209.
(19) Yamamori, Y.; Hiramatsu, Y.; Adachi, I. J. Heterocycl.
Chem. 1981, 18, 347.
Indole-3-carbonitrile
FVP of indole-3-carbaldoxime (613 mg, 3.8 mmol, 240 °C, 350 °C,
1 × 10–2 Torr, 25 min) over 3A MS using work-up Method A gave
indole-3-carbonitrile (484 mg, 89%) as an orange solid; mp 177–
181 °C (Lit.29 mp 183–184 °C).
1H NMR (DMSO-d6): d = 8.23 (1 H, s), 7.65–7.43 (2 H, m), 7.34–
7.15 (2 H, m).
(20) Wentrup, C.; Crow, W. D. Tetrahedron 1970, 26, 4375.
(21) Yamakawa, M.; Kubota, T.; Akazawa, H. Bull. Chem. Soc.
Jpn. 1967, 40, 1600.
13C NMR: d = 135.35 (Cq), 134.60, 126.87 (Cq), 123.54, 121.85,
118.57, 116.57 (Cq), 113.09, 84.36 (Cq).
(22) Salley, D. J.; Gray, J. B. J. Am. Chem. Soc. 1948, 70, 2650.
(23) Mai, K.; Path, G. Synthesis 1986, 1037.
Synthesis 2007, No. 20, 3179–3184 © Thieme Stuttgart · New York