Degradation of Three Related Bis(Pyridinium) Aldoximes in Aqueous Solutions at High Concentrations: Examples of Unexpectedly Rapid Amide Group Hydrolysis
Abstract
The principal initial degradation products of two bis(pyridinium) aldoxime organophosphate-inhibited acetylcholinesterase reactivators, 1 (HI-6) and 3 (HS-6), in concentrated nonbuffered aqueous solutions approximating potential therapeutic dosage concentrations were found to be the carboxylic acid derivatives 2 and 4 formed from the hydrolysis of the amide functional group. Compounds 2 and 4 were prepared by heating 1 and 3 in the presence of high concentrations of hydroxylamine hydrochloride and characterized by 1H and (13) C NMR, IR, and UV analyses. Estimates of the rates of hydrolysis of the amide groups in 1 and 3 and in model compounds 5, 7, and 8 under similar conditions were determined. The unexpectedly rapid hydrolysis of the amide groups in 1 and 3 was attributed to both the hydrogen ion catalysis of the concentrated aqueous solutions of the unusually acidic bis(pyridinium)aldoximes 1 and 3 and general acid catalysis by the aldoxime group.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1993
- Accession Number
- ADA270799
Entities
People
- Ming L. Shih
- William D. Korte
Organizations
- United States Army Medical Research Institute of Chemical Defense