Epimerization Studies of LSD Using 1H Nuclear Magnetic Resonance (NMR) Spectroscopy
Journal of Analytical Toxicology – October 01, 1997
Source: OpenAlex
Summary
The equilibrium concentration for the epimerization of d-lysergic acid diethylamide (LSD) to iso-LSD can be achieved under specific conditions. Starting with pure LSD, a 9:1 LSD/iso-LSD ratio is reached after one week at 45°C or two weeks at 37°C with a pH above 7.0. Conversely, converting iso-LSD back to LSD requires six weeks at 45°C and a pH of 9.7. This study employs proton NMR techniques to quantify these reactions, highlighting the challenges in extracting the epimerizable proton of iso-LSD.
Abstract
A study was conducted to determine the conditions needed to achieve the equilibrium concentration for the epimerization of d-lysergic acid diethylamide (LSD) to iso-LSD. The reaction was followed by integration of the C-9 resonance of LSD and iso-LSD by proton nuclear magnetic resonance (NMR). The C-9 resonance of LSD and iso-LSD appear as singlets at 6.35 and 6.27 ppm respectively. Starting with pure LSD, the conversion to iso-LSD is attained at temperatures above 37 degrees C and pH levels over 7.0. At a pH of 7.0 or higher, the LSD/iso-LSD ratio of 9:1 is achieved after one week at 45 degrees C or two weeks at 37 degrees C. Starting with iso-LSD, the conversion to LSD requires more vigorous conditions. The 9:1 LSD/iso-LSD ratio is attained only after 6 weeks at a temperature of 45 degrees C and a pH of 9.7. At lower pH levels, the reaction proceeds more slowly. The 9:1 LSD/iso-LSD ratio is achieved whether the starting material is LSD or iso-LSD and therefore represents an equilibrium concentration (K = 9). In addition, the more vigorous conditions needed to achieve equilibrium of iso-LSD to LSD demonstrate the difficulty in extraction of the epimerizable proton of iso-LSD. This study is the first to quantitate the epimerization of LSD by NMR techniques and establishes the conditions needed to induce epimerization in solution.