Synthesis of N-hydroxyacetaminophen, a postulated toxic metabolite of acetaminophen, and its phenolic sulfate conjugate

Publisher Website
Google Scholar
Abstract
Synthesis of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol), a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol), and its phenolic sulfate conjugate (postassium N-acetyl-N-hydroxy-p-aminophenyl sulfate) is described. Potassium p-nitrophenyl sulfate was reduced to the hydroxylamine, acetylated, and treated with sulfatase to yield N-hydroxyacetaminophen. The structures assigned are supported by the spectral data (IR, UV, MS [mass spectrometry], 1H NMR and 13C NMR). N-Hydroxyacetaminophen apparently was moderately unstable at physiological pH and temperature but its phenolic sulfate conjugate was stable.