Synthesis and EPR investigations of fluorocatecholamines

Abstract

The synthesis of 3-fluoro- and 5-fluoronoradrenaline (3- and 5-fluoronorepinephrine) starting from 4-fluorophenol or 3-fluoroanisole is described. In the first step the second OH group is introduced followed by O-methylation and subsequent introduction of an acetyl function by Friedel–Crafts acylation. Replacement of one acetyl proton by bromine and reaction with potassium phthalimide yields the adrenalone-type compounds. After cleavage of the methyl ethers and hydrazinolysis of the amide function the catecholamines were obtained by reduction of the carbonyl group.

Oxidation of the catechols obtained by the reduction leads to the corresponding semiquinone radicals which gave rise to well resolved EPR and, in some cases, ENDOR spectra. An assignment of the data obtained could be made by comparison of the variety of radicals investigated and with the help of multiresonance experiments. The 5-fluoro-o-benzosemiquinones are less stable than the 3-fluoro-radicals as can be seen by the formation of paramagnetic secondary products.