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N-Alkylation of an indole by substitution of an alkyl bromide; N-haloalkyl-2-toluenesulfonyl-indoles

SyntheticPage 15
DOI: 10.1039/SP15
Submitted Jun 18, 2001, published Jun 18, 2001
Stephen Caddick (

			Reaction Scheme: N-Alkylation of an indole by substitution of an alkyl bromide

Chemicals Used

Substrate (0.56 mmol)
KOH (powdered, 0.7 mmol)
1,3-dibromopropane (1.7 mmol)
DMF (3 ml)
hexane / ether (for chromatography)
Silica Gel (for chromatography)


To the substrate in DMF added the electrophile and then the KOH, stirred overnight at room temperature. Standard aqueous work up using ether for extraction. Purification by silica-gel chromatography using gradient elution (hexane:ether, 50:1, 20:1, 10:1, 5:1, 2:1) gave the product as a white solid (51%)

Author's Comments

We have used this type of reaction many times and although the yields are generally only in the range 40 - 70 oC it is generally quite applicable. It is important not to use too much base otherwise elimination can be a problem and dimerisation can be an issue. An alternative is to use a chloro-bromo substrate and convert the chloro compound into the bromide or iodide using NaBr or NaI.


1H NMR 7.85, 2H, d, J = 8.4 Hz; 7.71, 1H, d, J = 8.02 Hz; 7.44-7.37, 2H, m; 7.34-7.31 Hz, 2H, m; 7.22-7.16, 2H, m; 4.44, 2H, t, J = 7.8 Hz; 3.4, 2H, t, J = 6.25 Hz; 2.4, 3H, s; 2.22, 2H, p, J = 7.0 Hz

Lead Reference

S. Caddick, K. Aboutayab, K. Jenkins, R. I. West, J. Chem. Soc. Perkin Trans 1. 1996, 675

Other References

W. Dehaen, A. Hassner, J. Org. Chem. 1991, 56, 896

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Keywords: alkyl/alkenyl/aryl halides, aromatics/arenes, heterocyclic compounds, indole, nucleophilic, substitution

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