Synthesis and stability of isotopically labeled p-chloro-m-xylenol (PCMX)

• Published in: Pharmaceutical research Vol. 10; no. 10; p. 1466
• Main Authors: Reepmeyer, J C, Zielinski, Jr, W L, Leakey, J E, Si, Y
• Format: Journal Article
• Language: English
• Published: United States 01.10.1993
• Subjects: Anti-Infective Agents, Local - chemical synthesis; Anti-Infective Agents, Local - chemistry; Anti-Infective Agents, Local - metabolism; Catalysis; Chromatography, High Pressure Liquid; Drug Stability; Drug Storage; Gas Chromatography-Mass Spectrometry; Hydrogen-Ion Concentration; Isotope Labeling; Kinetics; Magnetic Resonance Spectroscopy; Tritium; Xylenes - chemical synthesis; Xylenes - chemistry; Xylenes - metabolism
• ISSN: 0724-8741
• DOI: 10.1023/A:1018975309429

The synthesis, reaction kinetics, and pH stability of isotopically labeled p-chloro-m-xylenol (PCMX) were evaluated. While base catalysis was more rapid than acid catalysis, the latter allowed the use of a cosolvent for deuterium and tritium labeling using as little as 250 microL labeled water. Both acid and base catalysis were markedly more rapid than that reported previously for the deuteration of PCMX and related phenols. Isotopic labeling occurred only at the 2 and 6 ring positions, ortho to the phenolic group of PCMX. No deuterium loss was observed after storage for 21 days at 37 degrees C over a pH range of 2-14. Isotopic loss was observed only below pH 2. The prepared 3H-labeled PCMX had a specific activity of 1.18 mCi/mmol, a radiochemical purity of 99.0%, and a chemical purity exceeding 99.0%, with a high stability during prolonged cold storage.