Degradation of three related bis(pyridinium)aldoximes in aqueous solutions at high concentrations: examples of unexpectedly rapid amide group hydrolysis.
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 13C 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.
Korte
W D
WD
U.S. Army Medical Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Shih
M L
ML
D000577:Amides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D011726:Pyridinium Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000577:Amides; D011726:Pyridinium Compounds