Geometry of lidocaine-like molecules: 2. Crystal structures of 2-benzyl-2-(1-piperidinyl)-N-(2,6-dimethylphenyl) acetamide and its hydrochloride hemihydrate
Ml. Glowka et A. Olczak, Geometry of lidocaine-like molecules: 2. Crystal structures of 2-benzyl-2-(1-piperidinyl)-N-(2,6-dimethylphenyl) acetamide and its hydrochloride hemihydrate, J CHEM CRYS, 29(6), 1999, pp. 695-700
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.