NMR of a series of novel hydroxyflavothiones

Alkylated hydroxyflavothiones, namely flavothione, 5-hydroxyflavothione, 5,7-dihydroxyflavothione (chrysinthione), 7-dodecyloxy-5-hydroxyflavothione, 7-butyloxy-5-hydroxyflavothione, 2',3,4',7-tetramethoxy-5-hydroxyflavothione, 3,3',4',7-tetra methoxy-5-hydroxyflavothione, 7-butyloxy-4',5-dihydroxyflavothione and 7-butyloxy-4',5-hydroxyflavanonethione have been synthesized from the corresponding hydroxyflavones in two steps, alkylation of the non-hydrogen-bonded hydroxyl groups by bromoalkanes or dimethyl sulfate followed by conversion of the carbonyl group to a thione using Lawesson's Reagent under microwave irradiation and solvent-free conditions. Part of the alkylated flavanone, 7-butyloxy-4',5-dihydroxyflavanone, was oxidized during the treatment with Lawesson's reagent to yield a second product 7-butyloxy-4',5-dihydroxyflavothione in addition to the target product butyloxy-4',5-hydroxyflavanonethione. Deuterium isotope effects on 13C chemical shifts have been measured in hydroxyflavones, isoflavones, flavanones and the thio analogs. Formal four-bond deuterium isotope effects on 13C chemical shifts, n Delta C=S(OD) are very sensitive to variations in structures and substitution patterns. Density functional theory (DFT) calculations are carried out to obtain geometries. Correlations relating distances around the hydrogen bond system to the deuterium isotope effects on 13C chemical shifts are discussed. 13C chemical shifts are calculated by DFT methods. Effects of thiocarbonyl anisotropies are suggested. Copyright (C) 2009 John Wiley & Sons, Ltd.