Preparation and Properties of 3-Indoleacetaldehyde
Reed A. Gray, Arch. Biochem. & Biophys. 81, 481-488 (1959)

3-Indoleacetaldehyde 

The method of preparation consisted of oxidation of tryptophan with dilute
sodium hypochlorite solution and was similar to the method used by Larsen (1)
except that a different oxidizing agent was used and precautions were taken to
prevent destruction of the aldehyde as it was being formed. The reaction is
based on that studied by Langheld (6) who showed that when an alpha-amino acid
is treated with sodium hypochlorite it is converted into an aldehyde containing
one less carbon atom than the original amino acid. The oxidation of alpha-amino
acids to aldehydes and nitriles has in fact been accomplished with a variety of
reagents (7).

EXPERIMENTAL METHODS AND RESULTS

Preparation of 3-Indoleacetaldehyde from Tryptophan

To 100 ml. of distilled water were added 15 ml. of 10% NaOH solution and 3.0 g.
of DL-tryptophan. After the tryptophan was completely dissolved, 4 N HCl was
added until tryptophan crystals just started to separate at a pH near 8.5. The
solution was diluted immediately with 1200 ml. of distilled water in a 4000-ml.
Erlenmeyer flask. To this solution was added 700 ml. benzene followed by 200 ml.
of 0.52% sodium hypochlorite solution made by mixing 1 part Clorox with 9 parts
water. The flask and contents were shaken with a swirling motion immediately
after the addition of the hypochlorite and during the entire duration of the
experiment so that the aldehyde was taken up in the benzene as soon as it was
produced. Care was taken to avoid an excess of hypochlorite which produced
brown-colored products. This also happened if dilute solutions were not used.
The flask was immersed in a hot water bath, and the temperature of the contents
was raised to 50 degrees C. over a period of 20 min. The temperature was held
between 50 and 51 degrees C. for 15 min. more. The benzene layer became yellow
in color and later turned orange. The benzene was separated from the aqueous
phase with a separatory funnel while still warm.

The benzene solution was concentrated to 65 ml. in a large evaporating dish
placed in a swift current of air in a fume hood. Slight heat was supplied with a
warm water bath at 40-50 degrees C. The resulting benzene solution was shaken
with 50 ml. of saturated sodium bisulfate solution in a closed wide-mouth
bottle. Crystals of the IAc.NaHSO3 formed immediately and were filtered almost
dry by suction.. The product was resuspended twice and shaken vigorously in 95%
ethanol and filtered each time. The crystals were washed again with absolute
alcohol and finally with ether. After drying at room temperature, the yield was
4.06 g. of white crystalline material. The yield was 90% of theoretical based on
the amount of tryptophan used. Most of the IAc.NaHSO3 was dissolved in a small
amount of water making a saturated solution. The solution was filtered, and the
IAc.NaHSO3 was recrystallized by adding absolute ethanol to a final
concentration of 90% ethanol, yielding 2.5 g. of recrystallized product.

To obtain the free aldehyde, 200 mg. of the IAc.NaHSO3 was dissolved in 8 ml.
water. A few drops of a saturated solution of Na2CO3 was added until the
solution turned slightly turbid. After standing a few minutes, the free aldehyde
was extracted by shaking the solution with three portions of peroxide-free
ether. After evaporation of the ether and drying at reduced pressure, 82 mg.
IAc was obtained as a colorless sirupy liquid.

Refs:

1. LARSEN, P., Dansk Botan. Ark. 11, 1 (1944).
6. LANGHELD, K., Ber. 42, 2306 (1909).
7. DEAKIN, H.D., Biochem. J. 12, 319 (1916).

