Organic Syntheses, CV 3, 479
Submitted by F. T. Tyson
Checked by R. L. Shriner and C. H. Tilford.
1. Procedure
A 2-l. three-necked round-bottomed flask is fitted with a reflux condenser and a glass inlet tube connected to a cylinder of nitrogen. The third opening of the flask is closed by a stopper. The top of the condenser is connected to an air trap which consists of two 500-ml. suction flasks joined in series. The first suction flask is empty; the second contains 100 ml. of paraffin oil, and the inlet tube of this flask extends slightly below the surface of the oil.
In the reaction flask is placed
600 ml. of commercial tert-butyl alcohol (Note
1), and the air in the flask is displaced by dry
nitrogen gas. Then
29 g. (0.75 gram atom) of metallic potassium is added, in portions, to the alcohol. The mixture is heated on a
water bath until all the
potassium has dissolved, and then
68 g. (0.5 mole) of o-formotoluide (Note
2) is added and brought into solution. The condenser is set for distillation with a filter flask as the receiver; this flask is protected from the air by connecting it to the trap used in the initial operation. The reaction flask is surrounded by a
metal bath, and the excess alcohol is removed by distillation. The residue is heated to 350–360° for about 20 minutes (Note
3) and then is allowed to cool in a stream of
nitrogen. The residue is decomposed by addition of 300 ml. of water, and the mixture is steam-distilled to remove the
indole. The distillate is extracted successively with
300 ml. and 100 ml. of ether, and the combined
ether extracts are shaken with cold dilute
5% hydrochloric acid to remove small amounts of
o-toluidine. The
ether extract is washed with 100 ml. of water, followed by
100 ml. of 5% sodium carbonate solution, and is dried over
20 g. of sodium sulfate. The
ether is removed by distillation, and the residue is distilled under reduced pressure.
Indole distils at
142–144°/27 mm. (
128°/10 mm.;
121°/5 mm.) as a pale yellow oil which solidifies and then melts at
52–53°. The yield is
23 g. (
79%) (Note
4).
2. Notes
1. Alcohols other than
tert-butyl alcohol, such as
methyl, ethyl, butyl, or isobutyl alcohol, may be used, but with a decrease in yield. If
methyl or ethyl alcohol is substituted for
tert-butyl alcohol, the
potassium should be added in smaller portions and the more vigorous reaction must be controlled by external cooling. Furthermore, if
methyl alcohol is used the amount of
potassium should be decreased from 0.75 gram atom to 0.5 gram atom.
2.
o-Formotoluide can be prepared by heating a mixture of
856 g. (8 moles) of o-toluidine and
403 g. (8.4 moles) of 90% formic acid on a
steam bath for about 3 hours and allowing the reaction mixture to stand overnight. The mixture is fractionated under reduced pressure; there is obtained
920–963 g. (
85–89%) of
o-formotoluide, b.p.
173–5°/25 mm., m.p.
55–58°. This product is a pale yellow solid which contains traces of
toluidine and possesses an odor indicating the presence of traces of an
isocyanide. However, the material is sufficiently pure for conversion to
indole. By use of
99% formic acid, a quantitative yield may be obtained. If a purer product is desired, the original reaction mixture is mixed with about a liter of water, the crude
formotoluide is filtered, then washed with 1%
hydrochloric acid and with water. After drying, the crude
formotoluide is recrystallized from
benzene-petroleum ether. The yield is practically the same as that obtained by direct distillation, and the product melts at
61°. In order to assure freedom from moisture, the recrystallized product may be distilled under reduced pressure; the loss in this distillation is negligible.
4. The product is pale yellow. The color may be removed by crystallizing the material from a mixture of
100 ml. of petroleum ether and about
10 ml. of ethyl ether. The recovery is
21 g. (
91%).
3. Discussion
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