Fischer indole synthesis in water: Simple, efficient preparation of naltrindole, naltriben and analogs

Romain A. Duval, John R. Lever

Research output: Contribution to journalArticle

Abstract

Naltrindole, naltrindole analogs and the benzofuran congener naltriben have been prepared by Fischer syntheses using mildly acidic, purely aqueous conditions. The preparation of naltrindole and several analogs was accomplished under almost neutral conditions using just the hydrochloride salts of naltrexone and various electron-rich and electron-poor phenylhydrazines in boiling water. The products were obtained by simple filtration in good to excellent yields and with high purities in the majority of cases. The route is suited to gram-scale synthesis, does not require the use of organic solvents, minimizes the use of corrosive acids, and is simple, efficient and environmentally friendly. Naltriben was prepared efficiently from the hydrochloride salts of naltrexone and O-phenylhydroxylamine but more forcing conditions, 6.0 N HCl, were required. A limitation to the method is the failure of Fischer cyclization between naltrexone and nitro-substituted phenylhydrazines under aqueous conditions.

Original languageEnglish (US)
Pages (from-to)304-309
Number of pages6
JournalGreen Chemistry
Volume12
Issue number2
DOIs
StatePublished - 2010
Externally publishedYes

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naltrindole
Phenylhydrazines
Naltrexone
Salts
salt
electron
Electrons
Water
Cyclization
Organic solvents
Boiling liquids
Caustics
water
Acids
acid
indole
naltrindole benzofuran

ASJC Scopus subject areas

  • Environmental Chemistry
  • Pollution

Cite this

Fischer indole synthesis in water : Simple, efficient preparation of naltrindole, naltriben and analogs. / Duval, Romain A.; Lever, John R.

In: Green Chemistry, Vol. 12, No. 2, 2010, p. 304-309.

Research output: Contribution to journalArticle

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