Protonated nitro group as a gas-phase electrophile: Experimental and theoretical study of the cyclization of o-nitrodiphenyl ethers, amines, and sulfides

Abstract

A novel gas-phase electrophilic cyclization, initiated by the protonation of a nitro group, occurs for 2-nitrophenyl phenyl ether and for the analogous sulfide and amine, leading to heterocyclic intermediates in each case. Subsequently, the cyclic intermediates dissociate via two pathways: (1) unusual step-wise eliminations of two OH radicals to afford heterocyclic cations, [phenoxazine − H] + , [phenothiazine − H] + and [phenazine + H] + , and (2) expulsion of H 2 O, to yield a heterocyclic ketone, followed by loss of CO. The proposed structures of the gas-phase product ions and reaction mechanisms are supported by chemical substitution, deuterium labeling, accurate mass measurements at high mass resolving power, product-ion mass spectra obtained by tandem mass spectrometry, mass spectra of reference compounds, and molecular orbital calculations. Using a mass spectrometer as a reaction vessel, we demonstrate that, upon protonation, a nitro group becomes an electrophile and participates in cyclization reactions in the gas-phase.

2-Nitrophenyl aryl sulfides undergo both intramolecular and electrospray-induced intermolecular oxidation of sulfur: An experimental and theoretical case study

“…Evidence for this latter process comes from accurate mass measurements, studies of reference compounds, MS/MS, and molecular modeling. The results complement our continuing studies of nitro aromatic compounds [14]. Uniting the two processes are fragmentations that raise the oxidation state of the sulfur atom.…”

“…Calculations by DFT reveal that the preferred site of protonation to form the [M + H] + of the mono-oxidized species is at the oxygen on the sulfur (Scheme 2), in contrast to one of the nitro-group oxygens as is the case for the [M + H] + of the unoxidized species [14]. Indeed, the SO site is preferred over the oxygens of the nitro group by > 30 kcal/mol.…”

“…Purity of the samples was checked by TLC, and the structures were confirmed by NMR, IR, and mass-spectrometric analyses, as described earlier [14]. Carbazole used for this study was purchased from Aldrich Chemical Co. (Milwaukee.…”

The Role of Methoxy Group in the Nazarov Cyclization of 1,5-bis-(2-Methoxyphenyl)-1,4-Pentadien-3-one in the Gas Phase and Condensed Phase

“…Combining the results with those from DFT calculations provides a useful approach in exploring reaction mechanisms, especially for protonated or deprotonated molecules. Examples are the investigation of mechanisms of the rearrangement of protonated 2-nitophenylphenyl ethers [14, 15] and that of the Smiles rearrangement [16, 17]. …”

Development of binding assays to screen ligands for Plasmodium falciparum thioredoxin and glutathione reductases by ultrafiltration and liquid chromatography/mass spectrometry

“…The study of nitro aryl derivatives by different mass spectrometric techniques has attracted great attention and interest in recent years because of their fragmentation process involving skeletal rearrangements [30]. A number of detection methods for nitro aryl and diaryl sulfides using positive and negative ion electrospray mass spectrometry experiments have been reported in the literature [31][32][33]. In this study, we report a new LC/MS method to detect compound 4 using negative electrospray MS.…”