demorol (Hive Bee)
12-11-02 11:53
No 388483
      Indole synthesis  Bookmark   

Here is a fairly simple synthesis of indole, taken from Organic Syntheses, CV 3, 479.


A 2L 3-necked RB 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 500mL suction flasks joined in series. The first suction flask is empty; the second contains 100mL of paraffin oil, and the inlet tube of this flask extends slightly below the surface of the oil.
In the reaction flask is placed 600mL of commercial tert-butyl alcohol (Note 1), and the air in the flask is displaced by dry nitrogen gas. Then 29g (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 68g (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 350360C for about 20 minutes (Note 3) and then is allowed to cool in a stream of nitrogen. The residue is decomposed by addition of 300mL of water, and the mixture is steam-distilled to remove the indole. The distillate is extracted successively with 300 mL and 100mL 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 100mL of water, followed by 100mL of 5% sodium carbonate solution, and is dried over 20g of sodium sulfate. The ether is removed by distillation, and the residue is distilled under reduced pressure. Indole distils at 142144C/27 mm (128C/10 mm; 121C/5 mm) as a pale yellow oil which solidifies and then melts at 5253C. The yield is 23g (79%) (Note 4).


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 856g (8 moles) of o-toluidine and 403g (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 920963g (8589%) of o-formotoluide, b.p. 173175C/25 mm, m.p. 5558C. 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.

3.) During this interval combustible gases, chiefly carbon monoxide and hydrogen, are evolved, and a liquid, which is principally o-toluidine, distils.

4.) The product is pale yellow. The color may be removed by crystallizing the material from a mixture of 100mL of petroleum ether and about 10mL of ethyl ether. The recovery is 21g (91%).

I can't find correct name for o-formotoluide. If anyone knows what is this chemicals correct name please tell me.

I'm dreaming of the white crystals.
12-11-02 12:19
No 388488
      o-formotoluidide = 2-formylamino-toluene ...  Bookmark   

o-formotoluidide = 2-formylamino-toluene (o-toluidine is 2-mino-toluene or 2-methyl-aniline):