The Solution Conformations of Lidocaine Analogues

IR and 1H NMR studies in CDCl3 and CCl4 of a series of tertiary aminoxylidides with the amino group in the 2 to 6 position of the acyl chain are described. Lidocaine, diethylaminoaceto-2',6'-xylidide, forms an intramolecular five-membered ring hydrogen-bonded monomer at all concentrations in both solvents. beta-Diethyl-amino-propiono-2',6'-xylidide forms an intramolecular six-membered ring hydrogen-bonded monomer in CDCl3 and CCl4 but a trans intermolecularly associated species is the major form present at high concentrations in CCl4. The longer-chain homologues are mixtures of nonassociated trans and cis monomers at low concentrations but associated trans forms predominate at high concentrations. Evidence for the presence of a hydrogen-bonded seven-membered ring intramolecular monomer in CDCl3 for gamma-diethylaminobutyro-2',6'-xylidide is presented. The relationship between the molecular conformation and the partition coefficient is discussed.