(Hive Bee)
07-21-03 22:02
No 448869
      Dehydrogenation of indolines
(Rated as: excellent)

Tetrahedron Letters 42 (2001) 5385–5387 (

A new mild and efficient dehydrogenation of indolines to indoles has been developed. For the dehydrogenation trichloroisocyanuric acid is used in combination with DBU. After work-up with sodium hydrogen sulfite it was possible to obtain indole in an almost quantitative yield. The new method is also suitable for indolines bearing electron withdrawing or electron donating groups. Under the reaction conditions no ring chlorination was observed.

Typical procedure:
Indoline 3a (6.0 g, 50.4 mmol) was dissolved in 60 ml MtB–ether, and 17.2 ml (2.3 equiv.) of DBU were added. The solution was cooled to -30°C and a solution of 4.55 g TCCA dissolved in a mixture of 75 ml MtB–ether and 25 ml ethyl acetate was added while maintaining the temperature below -20°C.
After completion of the addition the mixture was allowed to warm up slowly over 2 h to 0°C. After completion of the reaction, 50 ml of a saturated solution of sodium hydrogen sulfite was added while maintaining the temperature below 9°C. The mixture was stirred overnight at room temperature prior to separation of the phases.
The precipitated solid was filtered off and washed with 20 ml of MtB–ether. The phases were separated and the aqueous phase was extracted with 30 ml of MtB–ether. The combined organic phases were washed twice with 50 ml of water. The organic solution was filtered through a pad of silica gel (75 g) and the silica gel pad was subsequently washed with 100 ml of MtB–ether.
The combined organic phase was stripped to dryness and the residue was taken up in 100 ml of petroleum ether and 0.25 g of activated charcoal was added. The mixture was heated to reflux, filtered hot and the colorless solution was cooled slowly to -20°C. The obtained crystalline material was filtered off and dried giving 5.25 g of indole 4a as colorless crystals.

Entry Indoline  of type 3 Entry Indole of type 4 Yield
3a Indoline 4a Indole 89%
3b 3-Methyl-indoline 4b 3-Methyl-indole 82%
3c 2,3-Dimethyl-indoline 4c 2,3-Dimethylindole 81%
3d 5-Methoxy-indoline 4d 5-Methoxyindole 83%
3e 5-Nitro-indoline 4e 5-Nitro-indole 72%
3f 6-Nitro-indoline 4f 6-Nitro-indole 76%

Lego's voice: Unfortunately Lego has not found a method suitable for the large scale preparation of indolines but the search will go on. Nitrostyrenes can be cyclized to indoles but this is a small-scale photochemical synthesis.

A major advantage of this method is the workup which does not require chromatographical purification.

The candle that burns twice as bright burns half as long