¹H and ¹³C NMR Studies of Etidocaine Free Base and Hydrochloride Salt. Solvent and Temperature Dependence

Abstract

The ¹H and ¹³C NMR spectra of etidocaine free base, 1, and its hydrochloride salt, 2, have been examined at 200 MHz in a variety of solvents. Variable temperature ¹H NMR spectra of 2 were measured between 0° and 90°C at 500 MHz. Both ¹H and ¹³C spectra of the salt were strongly dependent on temperature, solvent and spectrometer frequency. Results are interpreted primarily as a consequence of acid-induced chirality at the amine nitrogen, resulting in solvent-dependent diastereoisomerism. Spectral complexity is explained as the result not only of diastereotopic nuclei due to the fixed “natural” chiral center at carbon, but also, in 2, to the presence of diastereomeric racemates resulting from the second chiral center (at nitrogen).

Key Words:

• Variable temperature NMR
• Local anesthetics
• Diastereotopic nuclei
• Diastereomers
• Nitrogen inversion
• Solventdependent diastereoisomerism
• Proton transfer
• Enantiomers
• NMR solvent effects