Org. Synth. 1963, 43, 58
DOI: 10.15227/orgsyn.043.0058
Submitted by H. M. Blatter, H. Lukaszewski, and G. de Stevens1.
Checked by Wayland E. Noland and Kent R. Rush.
1. Procedure
A mixture of 1.44 g. (0.0099 mole) of indole-3-carboxaldehyde,2 7.0 g. (0.053 mole) of diammonium hydrogen phosphate, 30 g. (30 ml., 0.34 mole) of 1-nitropropane, and 10 ml. of glacial acetic acid is refluxed for 12.5 hours. During the reflux period the pale-yellow mixture becomes dark red. The volatile reactants and solvent are removed under reduced pressure, and an excess of water is then added to the dark residue. After a short time, crude indole-3-carbonitrile precipitates rapidly. It is separated by filtration and dried under reduced pressure; weight 1.20–1.34 g. (85–95%). Crystallization from acetone-hexane, with decolorization by activated carbon, yields 0.68–0.89 g. (48–63%) of fairly pure indole-3-carbonitrile, m.p. 179.5–182.5° (Note 1).
2. Notes
1. The checkers obtained pure indole-3-carbonitrile, m.p. 182–184°, by subliming the product at a pressure of 1.5 mm. (bath temperature 165–170°) and recrystallizing the sublimate from a mixture of acetone and light petroleum ether. The recovery was 84%.
3. Discussion
Indole-3-carbonitrile has been prepared by the dehydration of indole-3-carboxaldehyde oxime,3,4,5 indole-3-glyoxalic acid oxime,4,6 or indole-3-carboxamide;3 by the action of cyanogen chloride on indolylmagnesium iodide;6 by the reaction of isoamyl formate with o-aminobenzyl cyanide in the presence of metallic sodium;7,8 by mild basic hydrolysis of 1-acetylindole-3-carbonitrile;7 and by the present method.9
4. Merits of the Preparation
This synthetic process is applicable to the preparation of other aromatic nitriles from aldehydes. The submitters have used it to prepare 5-bromoindole-3-carbonitrile, 7-azaindole-3-carbonitrile, p-chlorobenzonitrile, 3,4,5-trimethoxybenzonitrile, and p-N,N-dimethylaminobenzonitrile.9 There are several advantages to its use. They include (a) readily available and inexpensive reagents, (b) a simple, time-saving procedure, and (c) fair to good yields of nitrile obtained by a one-step method.

References and Notes
  1. Research Department, Division of Chemistry, CIBA Pharmaceutical Company, Division of CIBA Corporation, Summit, New Jersey.
  2. P. N. James and H. R. Snyder, Org. Syntheses, Coll. Vol. 4, 539 (1963).
  3. F. P. Doyle, W. Ferrier, D. O. Holland, M. D. Mehta, and J. H. C. Nayler, J. Chem. So., 2853 (1956).
  4. K. N. F. Shaw, A. McMillan, A. G. Gudmundson, and M. D. Armstrong, J. Org. Chem., 23, 1171 (1958).
  5. S. Swaminathan, S. Ranganathan, and S. Sulochana, J. Org. Chem., 23, 707 (1958).
  6. R. Majima, T. Shigematsu, and T. Rokkaku, Ber., 57, 1453 (1924).
  7. R. Pschorr and G. Hoppe, Ber., 43, 2549 (1910).
  8. N. I. Gavrilov, Izvest. Petrov. Selskochos, Akad. (Russia), 1–4, 14 (1919) [C. A., 19, 505 (1925)].
  9. H. M. Blatter, H. Lukaszewski, and G. de Stevens, J. Am. Chem. Soc., 83, 2203 (1961).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

petroleum ether

acetic acid (64-19-7)

acetone (67-64-1)

carbon (7782-42-5)

sodium (13966-32-0)

cyanogen chloride (506-77-4)

Indole-3-carboxaldehyde (487-89-8)

isoamyl formate (110-45-2)

Indole-3-carbonitrile (5457-28-3)

diammonium hydrogen phosphate (7783-28-0)

1-nitropropane (108-03-2)

acetone-hexane (821-55-6)

indole-3-carboxaldehyde oxime (2592-05-4)

indole-3-glyoxalic acid oxime


indolylmagnesium iodide




3,4,5-trimethoxybenzonitrile (1885-35-4)

p-chlorobenzonitrile (623-03-0)

o-aminobenzyl cyanide (2973-50-4)

p-N,N-dimethylaminobenzonitrile (1197-19-9)