Synthesis and structural investigation of salts of 2-amino-3-methylpyridine with carboxylic acid derivatives: an experimental and theoretical study.

Abstract

The salts bis(2-amino-3-methylpyridinium) fumarate dihydrate, 2C6H9N2+·C4H2O22-·2H2O (I), and 2-amino-3-methylpyridinium 5-chlorosalicylate, C6H9N2+·C7H4ClO3- (II), were synthesized from 2-amino-3-methylpyridine with fumaric acid and 5-chlorosalicylic acid, respectively. The crystal structures of these salts were characterized by single-crystal X-ray diffraction, revealing protonation in I and II by the transfer of a H atom from the acid to the pyridine base. In the crystals of both I and II, N-H...O interactions form an R22(8) ring motif. Hirshfeld surface analysis distinguishes the interactions present in the crystal structures of I and II, and the two-dimensional (2D) fingerprint plot analysis shows the percentage contribution of each type of interaction in the crystal packing. The volumes of the crystal voids of I (39.65 Å3) and II (118.10 Å3) have been calculated and reveal that the crystal of I is more mechanically stable than II. Frontier molecular orbital (FMO) analysis predicts that the band gap energy of II (2.6577 eV) is lower compared to I (4.0035 eV). The Quantum Theory of Atoms In Molecules (QTAIM) analysis shows that the pyridinium-carboxylate N-H...O interaction present in I is stronger than the other interactions, whereas in II, the hydroxy-carboxylate O-H...O interaction is stronger than the pyridinium-carboxylate N-H...O interaction; the bond dissociation energies also confirm these results. The positive Laplacian [∇2ρ(r) > 0] of these interactions shows that the interactions are of the closed shell type. An in-silico ADME (Absorption, Distribution, Metabolism and Excretion) study predicts that both salts will exhibit good pharmacokinetic properties and druglikeness.