Effects controlling the conformational selectivity and association parameters of H‐bonded assemblies between di‐ and triaminotriazines and bemegride

Abstract

Abstract2,4,6‐Tris(aminocyclohexyl)triazine (1) and 2,4‐bis(aminocyclohexyl)‐6‐methoxytriazine (2) are present in solution in two and three equilibrating conformations, respectively. The activation barrier for interconversion of the conformers 1a ⇌ 1b is 14·55 ± 0·2 kcal mol−1 (1 kcal = 4·184 kJ) and the activation barrier for interconversion of the conformers 2a ⇌ 2b ⇌ 2c is 14·2 ± 0·2 kcal mol−1. The conformational analyses of 1 and 2 were also followed by molecular mechanics calculations. Compounds 1 and 2 form H‐bonded intermolecular complexes with bemegride (3). Association of 3 proceeds by selection of a specific conformation of 1 and 2, i.e. 1b and 2a, respectively. The association constants of 3–1b and 3–2a are to Ka = 915 and 450 l mol−1, respectively. Molecular mechanics calculations for the H‐bonded intermolecular assemblies support the experimental observations of the selective conformational association.