Direct Observation of Acyl Nitroso Compounds in Aqueous Solution and the Kinetics of Their Reactions with Amines, Thiols, and Hydroxamic Acids

Abstract

Acyl nitroso compounds or nitrosocarhonyls (RC(O)N═O) are reactive short-lived electrophiles, and their hydrolysis and reactions with nucleophiles produce HNO. Previously, direct detection of acyl nitroso species in nonaqueous media has been provided by time-resolved infrared spectroscopy demonstrating that its half-life is about 1 ms. In the present study hydroxamic acids (RC(O)NHOH) are oxidized electrochemically in buffered aqueous solutions (pH 5.9-10.2) yielding transient species characterized by their maximal absorption at 314-330 nm. These transient species decompose via a first-order reaction yielding mainly HNO and the respective carboxylic acid and therefore are ascribed to RC(O)N═O. The sufficiently long half-life of RC(O)N═O in aqueous solution allows for the first time the study of the kinetics of its reactions with various nucleophiles demonstrating that the nucleophilic reactivity follows the order thiolate > hydroxamate > amine. Metal chelates of CHC(O)NHOH catalyze the hydrolysis of CHC(O)N═O at the efficacy order of Cu > Zn > Ni > Co where only Cu catalyzes the hydrolysis also in the absence of the hydroxamate. Finally, oxidation of hydroxamic acids generates HNO, and the rate of this process is determined by the half-life of the respective acyl nitroso compound.

Multiscale modelling of the radical-induced chemistry of acetohydroxamic acid in aqueous solution

“…The transient nitroxide radical (CH 3 CONHOc), formed in the AHA reaction with the cOH radical and other minor carbon radical species undergoes bimolecular combination according to eqn (3), resulting in an acyl nitroso (CH 3 CON]O). Acyl nitroso compounds are unstable and have been shown to undergo hydrolysis as follows: 75,76 The HNO formed undergoes bimolecular combination with itself to ultimately yield H 2 O and N 2 O according to: [77][78][79]…”

Pentacyanoferrate(II) complex of pyridine-4- and pyrazine-2-hydroxamic acid as source of HNO: investigation of anti-tubercular and vasodilation activities

“…Another possibility is thus that, in the hydroxamic series, the carboxylic acid does not arise from an aroyl radical, but from another intermediate instead. This intermediate could be the undissociated aroyl-nitroso compound, generated upon an oxidation step, which could undergo a rapid heterolytic cleavage by the surrounding water molecules (Scheme 6), releasing HNO without any radical species, as previously suggested to occur from other hydroxamic acids [38,39].…”

tert-Butyl Nitrite as a Twofold Hydrogen Abstractor for Dehydrogenative Coupling of Aldehydes with N-Hydroxyimides

“…t BuOH and HNO (BDE of 49.6 kcal/mol) could then be recycled to synthesize t BuONO using O 2 as the oxidant, releasing no NO x waste. The reaction without NHPI gives neither 3 nor acyl nitroso compound, indicating acyl-NO is not involved . The abstraction of the H atom of NHPI by NO was proven by the coupling of p -anisaldehyde with NHPI directly using NO gas (Scheme b) …”

“…The reaction without NHPI gives neither 3 nor acyl nitroso compound, indicating acyl-NO is not involved. 16 The abstraction of the H atom of NHPI by NO was proven by the coupling of p-anisaldehyde with NHPI directly using NO gas (Scheme 2b). 17 The optimal reaction conditions were established, and either aliphatic or aromatic aldehydes afford corresponding NHPI esters in ≤99% yields (Scheme 3).…”