The synthesis of (iodobenzyl)oxybenzaldehydes, useful intermediates for biologically active targets

Hedvig Bölcskei, Andrea Német-Hanzelik, István Greiner, Zsófia Dubrovay, Viktor Háda, G. Keglevich

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The benzyloxy-benzyl moiety is a valuable building block in medicinal chemistry, e.g. in case of the voltage gated sodium channel blockers Safinamide and Ralfinamide. To prepare further derivatives a series of (iodobenzyl)oxybenzaldehydes (3a-3i) useful intermediates for the synthesis of biologically active compounds were synthesized in high yields by O-benzylation of 2-, 3- and 4- hydroxybenzaldehydes (2a-2c) with a variety of iodobenzylbromides (1a-1c). The title compounds were obtained in 77-100 % yield in 2-5 hours. Longer reaction time or addition of water favoured the formation of aldol-type by-products, mainly 4-hydroxy-4-{[(iodophenyl)methoxy]phenyl}butan-2-one derivatives (5a-5g), which contained the iodine group and the 4-hydroxy-butan-2-one moiety in various positions. In one case (3E-)-4-{3-[(2-iodophenyl)methoxy]phenyl}but-3-en-2-one (6c) with a double bond has been isolated. These side-reactions could be avoided by using acetonitrile as solvent. The structures of the new products were established by high resolution MS and NMR measurements, where 1H-1H, direct 1H-13C, long-range 1H-13C scalar spin-spin connectivities were established from 1D 1H, 13C, 2D gHSQCAD, zTOCSY and gHMBCAD NMR experiments.

Original languageEnglish
Pages (from-to)233-239
Number of pages7
JournalLetters in Drug Design and Discovery
Volume14
Issue number2
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Voltage-Gated Sodium Channel Blockers
Pharmaceutical Chemistry
Iodine
Water
safinamide
3-hydroxybutanal
acetonitrile
Ralfinamide
Proton Magnetic Resonance Spectroscopy
3-hydroxybenzaldehyde
4-hydroxybenzaldehyde

Keywords

  • (Iodobenzyloxy)benzaldehydes
  • Aldol condensation
  • Aldol reaction
  • Alkylation
  • Hydroxybenzaldehyde
  • Iodobenzylbromide

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

The synthesis of (iodobenzyl)oxybenzaldehydes, useful intermediates for biologically active targets. / Bölcskei, Hedvig; Német-Hanzelik, Andrea; Greiner, István; Dubrovay, Zsófia; Háda, Viktor; Keglevich, G.

In: Letters in Drug Design and Discovery, Vol. 14, No. 2, 01.01.2017, p. 233-239.

Research output: Contribution to journalArticle

Bölcskei, Hedvig ; Német-Hanzelik, Andrea ; Greiner, István ; Dubrovay, Zsófia ; Háda, Viktor ; Keglevich, G. / The synthesis of (iodobenzyl)oxybenzaldehydes, useful intermediates for biologically active targets. In: Letters in Drug Design and Discovery. 2017 ; Vol. 14, No. 2. pp. 233-239.
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