GEOMETRY OF LIDOCAINE-LIKE MOLECULES .1. CRYSTAL-STRUCTURE OF TOCAINIDE

The title compound crystallizes in the orthorhombic space group P2(1)2 (1)2(1), With Z = 4, a = 4.770(1)Angstrom, b = 6.620(1)Angstrom, c = 3 7.550(7)Angstrom, R = 0.04. The most important factors affecting confo rmation of the molecules are: the protonation state of the N(9) atom a nd ortho-substitution of the benzene ring in the acetanilide system. P rotonation promotes an extended form of the molecule and 2,6-substitut ion forces a twist of at least 60 degrees between the benzene ring and amide group planes, The resulting separation of lipophilic (xylidine) and amine groups, being two important pharmacophores, equals about 5 Angstrom in tocainide and all other structures comprising the amino-2, 6-dimethylacetanilide system.