Crystal structures of ester derivatives of 2,6-bis(1-pyrrolidinylmethyl)-4-benzamidophenol antiarrhythmic agents

Abstract

The N atoms in both of the pyrrolidine rings in the title compounds are protonated which prevents the formation of an intramolecular hydrogen bond between the phenol OH group and the ring N atom. This hydrogen bond is thought to be important for maintaining the active shape of these drugs. The positions of the pyrrolidine rings are determined by a chain of hydrogen bonds which link the N+−H through the Cl− back to portions of the same molecule. In both molecules, the carbonyl bond of the ester substituent is aligned parallel to the carbonyl bond of the central amide. The benzanilide fragment is flattened relative to the common conformation found in tabulated structures. Extensive hydrogen bonding is observed due to the presence of solvent and chloride ions. Compound1, 2,6-bis(1-pyrrolidinylmethyl)-4-(4-carboethoxybenzamido)phenol, crystallizes as the dihydrochloride methanol hydrate in the monoclinic space group C2/c with 8 molecules per unit cell and cell constants:a=20.3013,b=11.296(2),c=24.901(5)A, β=93.19(1)°, 4945 unique reflections, 2946 observed,R=0.071. Compound2, 2,6-bis[1-pyrrolidinylmethyl-4-[4-(2-carboethoxyethyl)benzamido]phenol, crystallizes as the dihydrochloride salt in the monoclinic space group P21/c with 4 molecules per unit cell anda=12.903(3),b=16.430(4),c=13.731(2)A, β=103.64(2)°, 5712 unique reflections, 2449 observed,R=0.057.