The Reaction of Peroxynitrite with Morpholine (Secondary Amines) Revisited: The Overlooked Hydroxylamine Formation

Abstract

In memoriam Hanns FischerThe reaction of peroxynitrite/peroxynitrous acid with morpholine as a model compound for secondary amines is reinvestigated in the absence and presence of carbon dioxide. The concentration-and pHdependent formation of N-nitrosomorpholine and N-nitromorpholine as reported in three previous papers ([25] [26] [14]) is basically confirmed. However, 13 C-NMR spectroscopic product analysis shows that, in the absence of CO 2 , N-hydroxymorpholine is, at pH ! 7, the major product of this reaction, even under anaerobic conditions. The formation of N-hydroxymorpholine has been overlooked in the three cited papers. Additional (ring-opened) oxidation products of morpholine are also detected. The data account for radical pathways for the formation of these products via intermediate morpholinederived aminyl and a-aminoalkyl radicals. This is further supported by EPR-spectrometric detection of morpholine-derived nitroxide radicals, i.e., morpholin-4-yloxy radicals. N-Nitrosomorpholine, however, is very likely formed by electrophilic attack of peroxynitrite-derived N 2 O 4 .15 N-CIDNP Experiments establish that, in the presence of CO 2 , N-nitro-and C-nitromorpholine are generated by radical recombination. The present results are in full accord with a fractional (28 AE 2%) homolytic decay of peroxynitrite/peroxynitrous acid with release of free hydroxyl and nitrogen dioxide radicals.

N-Nitrosodimethylamine Formation during UV/Hydrogen Peroxide and UV/Chlorine Advanced Oxidation Process Treatment Following Reverse Osmosis for Potable Reuse

“…This behavior concurs with the observation that NDMA formation via these dark breakpoint reactions occurred within 10 min, with no significant formation thereafter (Figure 2). Reactions associated with eqs 9 and 10 are more likely to be associated with NDMA formation than those associated with eqs 7 and 8 because (1) the observed pattern of NDMA formation more closely matched that of In previous research regarding NDMA formation via breakpoint reactions at pH 6.9, 32 we had suggested that HNO (pK a ∼ 7) 34 formation led to the formation of • NO and • OH via peroxynitrous acid (ONOOH; pK a = 6.8) 35 and its conjugate base, peroxynitrite (ONOO − ) 35 (eqs 2 and 3). Indeed, when HOCl was applied to 840 μM NH 4 Cl and 50 μM DMA in the presence of 50 mM of the radical scavenger, tert-butanol, NDMA formation declined by 94% for reactions conducted at pH 5.7 at a 3:1 Cl 2 /N ratio and at pH 6.9 at a 2:1 Cl 2 /N ratio.…”

“…32 NDMA formation was suggested to arise from nitroxyl (HNO; pK a ∼ 7) 34 formation by hydrolysis of NHCl 2 during breakpoint chlorination. Subsequent reactions of NO − (the conjugate base of HNO) with dissolved oxygen could form peroxynitrous acid (ONOOH) and peroxynitrite (ONOO − ) and thence nitric oxide ( • NO; eq 2) 35 and hydroxyl radicals ( • OH; eq 3). 35 Amine radicals formed by amine reactions with • OH could form NDMA by combination with • NO.…”

N‐Nitrosomelatonin: synthesis, chemical properties, potential prodrug

“…The second compound able to nitrosate N ‐terminal blocked tryptophan derivatives at physiological pH is peroxynitrite [13, 16, 18, 19]. Recently, we [20] confirmed a hypothesis of Williams [21] that the peroxynitrite‐induced nitrosation of various compounds proceeds via N 2 O 4 , which is somewhat less effective as electrophilic, amine‐nitrosating agent than N 2 O 3 [22]. In addition, peroxynitrite nitrates melatonin at various positions (N‐1, C‐4 and C‐6) [23].…”

Product Class 5: Hydroxylamines

“…[224][225][226][227][228] In addition, the oxidative metabolism of secondary amines produces N,N-dialkylhydroxylamines. [229][230][231][232] Methods for N,N-dialkylhydroxylamine preparation have been reviewed up to 1990 (see Houben-Weyl, Vol. E 16a, p 214) [4,7,233] and refer mainly to the alkylation of either for references see p 1066 free hydroxylamine or N-monosubstituted hydroxylamines, to the reduction of nitrones, to the addition reactions of organometallic compounds to nitrones, to the pyrolysis of trialkylamine N-oxides (Cope reaction), and to the oxidation of secondary amines.…”