Synthon Competition and Cooperation in Molecular Salts of Hydroxybenzoic Acids and Aminopyridines

Abstract

Meta- and para-substituted hydroxy-benzoic acids and amino-pyridines were cocrystallized and characterized by X-ray diffraction. Proton transfer from the COOH to pyridyl N acceptor (PyN) occurred in 11 molecular salts (1−11) leading to a PyNH+···−OOC ionic synthon in 10 structures and a PyNH+···O═C hydrogen bond in one structure. Competition and cooperation between COO−, OH, NH2, PyNH+, and H2O functional groups for the observed hydrogen bond synthons are examined in 11 structures, of which 4 are hydrates. The second and third highest occurring synthons are NH2···OH, NH2···−OOC, and OH···−OOC in nine, eight, and eight structures, respectively. Hydrogen bonding of water to/from COO−, OH, and NH2 groups is present in hydrates 1, 5, 7, and 9. There are no systematic studies on our knowledge on hydrogen bond competition and interplay when the above four common functional groups are present in the same crystal structure. Synthons in this study are compared with statistics extracted from the Cambridge Structural Database to summarize trends and predict hydrogen bonding in new cocrystal and salt structures. The term molecular salt is suggested for ionic complexes derived from organic acids and bases. Acidity constants of benzoic acids and amino-pyridines were calculated in the gas phase, MeOH, and water using the SPARC program. The ΔpKa rule is found to be inadequate for predicting neutral or ionic O−H···N/N+−H···O− hydrogen bonds when other polar functional groups are also present in the system. The persistence of PyNH+···−OOC ionic synthons is ascribed to the presence of OH and NH2 groups in the same supramolecular system. ΔpKa values are in the range 1−5 in the gas phase and water but negative in MeOH (−1 to −6), on the whole lower than the pKa difference of >3 that is generally accepted as a condition for proton transfer. Our results are at variance with a recent paper in Cryst. Growth Des. (2008, 8, 4533−4545) wherein neutral COOH···NPy heterosynthon occurs with 78% probability when competition in the presence of phenol OH group only was analyzed.