Synthesis of N-alkyl-3-hydroxy-2(1H)-pyridinones and coordination complexes with iron(III)

The amidation of 2,5-dimethoxytetrahydrofuran-2-carboxylic acid methyl ester by primary alkylamines followed by acid-catalyzed rearrangements yields N-alkyl-3-hydroxy-2-pyridinones. The rearrangement reaction is promoted by the presence of metal ions, such as Fe3+, Cu2+, and Zn2+, which have high affinities for the bidentate hydroxypyridinone binding group. The structures of N-butyl-3-hydroxy-2-pyridinone (HL') and its 3:1 complex with iron(III) (FeL'3·3H2O) have been determined by x-ray crystallography. Bond lengths involving the pyridine ring indicate that a catechol-like aromatic resonance form is significant, particularly in the iron complex. The visible spectra for [FeL'n](3-n)+ (n = 1-3) are virtually identical with those of previously characterized complexes of iron(III) and 3-hydroxy-2-(1H)-pyridinone (3,2-Hopo, HL). The log Ka (protonation constant) of HL' and log K3 for formation of FeL'3 (from FeL'2+ and [L']-) are higher by 0.5 log unit than those of the unsubstituted HL and FeL3. Differences in equilibria at pH > 7 between solutions of FeL'3 and those of FeL3 have been studied by spectrophotometric titrations. The N-butyl derivative FeL'3 hydrolyzes only above pH 10.5 in the presence of 3 mM excess HL', whereas three stepwise protonations (log Ka = 9.2, 10.6, 12) are observed in solutions of FeL3 containing excess (several millimolar) HL. The contrasting behaviors of FeL'3 and FeL3 in alkaline solution are rationalized in terms of the absence or presence of a weakly acidic proton on the ligand nitrogen. 38 refs., 8 figs., 5 tabs