New 4-hydroxy-N-(2-hydroxyethyl)butanamides: Structure and acidity

Optically active new 4-hydroxy-N-(2-hydroxyethyl)butanamides are reported. The structure in the solid state of four racemic mixtures and three enantiomeric pure compounds was determined by X-ray diffraction. The solid state arrangements of enantiomerically pure compounds were compared with those of their racemic mixtures. The butanamides prefer lineal conformations in the solid state. They form dimers and polymers through intermolecular hydrogen bonds. Variable temperature 1H NMR experiments were performed in order to analyse the strength of the hydrogen bonds in the neutral molecules in solution. The pKa values of the dihydroxybutanamides in DMSO determined by cyclic voltammetric (11.1–14.5) were lower than those reported for amides RNHCOR without hydroxyl groups (25.9). The latter motivated us to investigate the role of hydrogen bonds in the stabilization of the corresponding anions and in consequence in the acidity of the amides. The explanation of the enhanced NH acidity of dihydroxybutanamides was found in the cyclic voltammetric experiments, in conductimetric titrations using nBu4NOH in methanol and titration with CsOH in acetonitrile. The optimised structures for the neutral molecules and their mono and dianions calculated by ab-initio HF(6-31 + G∗) and B3LYP(6-31 + G∗) methods supported the explanation of the enhanced NH acidity.