Indole → 1,2,3,4-Tetrahydrocarbazole

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Reaction Steps

In Scheme II, Step A, a phenylhydrazine salt (for example the hydrochloride salt) of formula (4), is reacted with a cyclic ketone of formula (3) in a Fischer indole synthesis to provide a tetrahydrocarbazole of formula (5). The hydrazine and ketone are reacted in ethanol saturated with hydrogen chloride gas at reflux for about 10 to 48 hours and isolated using standard aqueous workup techniques. Alternatively the reaction can be accomplished without the hydrogen chloride gas simply by using a phenyl hydrazine hydrochloride salt of formula (4) with a ketone of formula (3) in ethanol at about 50 to 85° C. for about 10 to 72 hours. In yet another procedure a phenylbydrazine hydrochloride salt of formula (4) and a ketone of formula (3) can be reacted as a vigorously stirred heterogeneous mixture in water and concentrated hydrochloric acid at about 80 to 100° C. for about 4 to 8 hours as essentially described in U.S. Pat. No. 6,359,146B1. The tetrahydrocarbazole can then be isolated by filtration. Using yet another variation, acetyl chloride and absolute ethanol are stirred at 0° C. to room temperature for about 1 to 2 hours. A phenylhydrazine hydrochloride salt of formula (4) and a ketone of formula (3) are then added to the ethanol/HCl and reluxed for about 10 to 72 hours.

Provenance & Evidence