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The Synthesis of (Iodobenzyl)oxybenzaldehydes, Useful Intermediates for Biologically Active Targets

[ Vol. 14 , Issue. 2 ]


Hedvig Bölcskei, Andrea Német-Hanzelik, István Greiner, Zsófia Dubrovay, Viktor Háda and György Keglevich   Pages 233 - 239 ( 7 )


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.


Alkylation, hydroxybenzaldehyde, iodobenzylbromide, (iodobenzyloxy)benzaldehydes, aldol reaction, aldol condensation.


Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521, Budapest, Hungary.

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