Jump to main content
Jump to site search

Issue 32, 2013
Previous Article Next Article

Indolesvia Knoevenagel–Hemetsberger reaction sequence

Author affiliations


A series of substituted indoles have been synthesized by the sequential reaction of aromatic aldehydes with ethyl azidoacetate in the presence of sodium ethoxide to form the corresponding ethyl α-azido-β-arylacrylates (Knoevenagel process) followed by a solvent mediated thermolysis (Hemetsberger process). The isolated yields of the ethyl α-azido-β-arylacrylates were significantly increased when employing the sacrificial electrophile ethyl trifluoroacetate. 1H NMR and coupled 1H–13C NMR analysis of the ethyl α-azido-β-arylacrylates indicate that the condensation is stereospecific—only the Z-isomer could be detected. Solvent mediated thermal treatment of the meta-substituted ethyl α-azido-β-arylacrylates resulted in the formation of both the 5- and 7- substituted indoles—the 5-regioisomer being slightly favored over the 7-regioisomer. Analogous thermal treatment of (2Z, 2Z′)-diethyl 3,3′-(1,3-phenylene)bis(2-azidoacrylate) and (2Z, 2Z′)-diethyl 3,3′-(1,4-phenylene)bis(2-azidoacrylate) exclusively produced pyrroloindoles, diethyl 1,5-dihydropyrrolo[2,3-f]indole-2,6-dicarboxylate and diethyl 1,5-dihydropyrrolo[2,3-f]indole-2,6-dicarboxylate, respectively. Results are also reported which indicate that the α-azido-β-arylacrylates can be used in the subsequent Hemetsberger indolization process without prior purification.

Graphical abstract: Indoles via Knoevenagel–Hemetsberger reaction sequence

Back to tab navigation

Supplementary files

Article information

16 Apr 2013
31 May 2013
First published
31 May 2013

RSC Adv., 2013,3, 13232-13242
Article type

Indoles via Knoevenagel–Hemetsberger reaction sequence

W. L. Heaner IV, C. S. Gelbaum, L. Gelbaum, P. Pollet, K. W. Richman, W. DuBay, J. D. Butler, G. Wells and C. L. Liotta, RSC Adv., 2013, 3, 13232
DOI: 10.1039/C3RA42296H

Social activity

Search articles by author