Tautomerism and ionization processes in 6-thioxanthine and its N-methyl derivatives

U.v. and n.m.r. spectra have been measured for 6-thioxanthine and all its N-methyl derivatives. In aqueous solutions of 6-thioxanthines with a free NH-group in the imidazole ring, the 7-NH-tautomer is predominant, while the monoanion of 6-thioxanthine and its 1-methyl derivative are mainly present as the 9-NH-tautomers. Whenever possible, anion formation occurs first by dissociation of the 3-NH-group; the order of acidities is 3 > 7 > 1. The anions of 6-thioxanthine and its 1-methyl derivative tautomerize to the 9-NH form. Steric interactions between substituents (H and Me) at positions 3 and 9 are evident in the pK values of the 9-methyl-6-thioxanthines and in the large displacement to lower field of the n.m.r. signals of the 3- and 9-methyl groups in 3,9-dimethyl derivatives.