Org. Synth. 1963, 43, 58
DOI: 10.15227/orgsyn.043.0058
INDOLE-3-CARBONITRILE
Submitted by H. M. Blatter, H. Lukaszewski, and G. de Stevens
1.
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.
Appendix
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
indole-3-carboxamide
indolylmagnesium iodide
1-acetylindole-3-carbonitrile
5-bromoindole-3-carbonitrile
7-azaindole-3-carbonitrile
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)
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