Synthesis, tautomeric forms, specific intermolecular interactions, and lipophilicity of methylated 6-hydroxypyridazine-3-carboxylic acid and its 4,5-dihydro analogs

Effects of methylation for intermolecular interactions and lipophilicity have been studied for a series of methylated 4,5-dihydro-6-hydroxypyridazine-3-carboxylic and 6-hydroxypyridazine-3-carboxylic acids (1 and 2). In solution they exist in equilibrium of the lactam and lactim tautomers, with the reverse preferences for analogs 1 and 2, which affect the syntheses of their methylated derivatives. Carboxylic acid 2 preferably crystallizes as a hydrate, built of carboxylate anions and hydronium cations 2(-)center dot H3O+, hydrogen bonded into catemeric patterns involving both ions. In methyl 4,5-dihydro-6-oxopyridazine-3-carboxylate (4A) the molecules are NH center dot center dot center dot O hydrogen bonded into chains. In both structures 2(-)center dot H3O+ and 4A, there are relatively strong CH center dot center dot center dot O hydrogen bonds, arranging the molecules into sheets. The increased lipophilicity of the methylated derivatives has been correlated with the formation of CH center dot center dot center dot O bonds. (C) 2011 Elsevier B.V. All rights reserved.