Geometry of lidocaine-like molecules: 2. Crystal structures of 2-benzyl-2-(1-piperidinyl)-N-(2,6-dimethylphenyl) acetamide and its hydrochloride hemihydrate

The title compounds both crystallize in the monoclinic space group P2(1) (Z = 4), with a = 12.574(1), b = 9.653(1) c = 16.483(1) Angstrom, and beta = 91.84(1)degrees for the free base and a = 10.991(2), b = 16.864(3), c = 12. 030(2) Angstrom, beta = 99.35(3)degrees for the hydrochloride. The most imp ortant factors affecting conformation of the molecules are: ortho-substitut ion of the benzene ring in the acetanilide system and substitution of the C -alpha atom. Surprisingly, the conformation does not depend on the protonat ion state of the amine nitrogen atom, which greatly affects packing and hyd rogen bonding patterns in the crystalline state. The conformation in which the H atom of the charged amine group is in a trans position to the main ba ckbone of the molecule, is probably responsible for the antiarrhythmic acti vity, while a gauche conformation promotes local anaesthetic action. The se paration of the lipophilic (xylidine) and amine groups, being two important pharmacophores, equals about 4.7 Angstrom in the studied compounds and oth er structures comprising the amino-2,6-dimethyl-acetanilide system.