Title:The Synthesis of (Iodobenzyl)oxybenzaldehydes, Useful Intermediates for Biologically Active Targets
VOLUME: 14 ISSUE: 2
Author(s):Hedvig Bölcskei, Andrea Német-Hanzelik, István Greiner, Zsófia Dubrovay, Viktor Háda and György Keglevich
Affiliation:Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521, Budapest, Hungary.
Keywords:Alkylation, hydroxybenzaldehyde, iodobenzylbromide, (iodobenzyloxy)benzaldehydes, aldol reaction, aldol condensation.
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.
