The Degradation of 4-Morpholinoaniline in Aqueous Solution

Abstract

The reactivity of 4-morpholinoaniline with water was examined in aqueous solutions at pH 1 – 4. Two dissociation constant values were identified for 4-morpholinoaniline using spectrophotometric titration: pKa1, which was assigned to the aniline ammonia nitrogen, was 1.8 and pKa2, assigned to the morpholine nitrogen, was 4.9. At pH < pKa1, 4-morpholinoaniline reacted with water to form 4-morpholinophenol, which further degraded to hydroquinone. The hydrolytic degradation reactions of 4-morpholinoaniline to 4-morpholinophenol and 4-morpholinophenol to hydroquinone both exhibited pseudo-first order kinetics under these reaction conditions. 4-Morpholinophenol is proposed to form by nucleophilic aromatic substitution of the aniline ammonia by water via an intermediate whose electron-rich aromatic ring is electrostatically stabilized by the positive charge on the morpholino nitrogen and the positive charge on the incoming nucleophilic water molecule. As pH exceeded pKa1 and the aniline ammonia nitrogen was deprotonated, the nucleophilic aromatic substitution reaction was disfavored and accounted for less than 10% of 4-morpholinoaniline degradation at pH ≥ 2.5. Instead, 4-Morpholinoaniline degradation in these higher pH aqueous solutions yielded multiple degradation products, and the kinetics of 4-morpholinoaniline degradation were more complicated than zero-, first-, or second-order. Characterization and structural identification of the major degradation product observed in these higher pH solutions yielded a highly conjugated molecule that appears to be a dimerization product. Without identification of intermediates or additional degradation products observed by chromatography, the mechanism by which this product forms could not be resolved; however, metal catalysis and direct reaction of 4-morpholinoaniline with 4-morpholinophenol were disproven.