Generation of arylnitrenium ions by nitro-reduction and gas-phase synthesis of N-Heterocycles

Abstract

Nitro-reduction by the vinyl halide radical cation CH2 = CH-X+* (X = Cl or Br) converts nitroaromatics into arylnitrenium ions, significant intermediates in carcinogenesis, and the present study reports on the scope and regioselectivity of this versatile reaction. The reaction is general for different kinds of substituted nitroaromatics; para/meta substitutents have little effect on the reaction while ortho substitutents result in low yields of arylnitrenium ions. The phenylnitrenium ion PhNH+ can be generated by chemical ionization (CI) of nitrobenzene using 1,2-dichloroethane as the reagent gas or by atmospheric pressure chemical ionization (APCI) of 1,2-dichloroethane solution doped with nitrobenzene. The chemical reactivities of the arylnitrenium ions include one-step ion/molecule reactions with nucleophiles ethyl vinyl ether and 1,3-dioxolanes, respectively, involving the direct formation of new CN bonds and synthesis of indole and benzomorpholine derivatives. The indole formation reaction parallels known condensed phase chemistry, while the concise morpholine-forming reaction remains to be sought in solution. The combination of collision-induced dissociation (CID) with novel ion/molecule reactions should provide a selective method for the detection of explosives such as TNT, RDX and HMX in mixtures using mass spectrometry. In addition to the reduction of the nitro group, reduction of methyl phenyl sulfone PhS(O)2Me to the thioanisole radical cation PhSMe+* occurs using the same chemical ionization reagent 1,2-dichloroethane. This probably involves an analogous reduction reaction by the reagent ion CH2 = CH-Cl+*.

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

“…We explored the protonation, cyclization and subsequent fragmentation of protonated 2-nitrophenyl phenyl ether (1), sulfide (5) and amine (9). Protonation of the nitro-group oxygen indeed makes the nitrogen an electrophile and 2′-attachment is the first step in cyclization, forming a tricyclic core from which the lowmass groups are eliminated, resulting in the proposed cyclic product ions.…”

“…The acid-catalyzed rearrangement of allyl phenyl ether, using chemical ionization (CI) mass spectrometry, is one example of the utility of mass spectrometry in this area [8]. A recent report by Cooks and coworkers [9] on the reduction of nitro aromatic compounds to arylnitrenium ions in the gasphase by radical cations of vinyl halides demonstrate that 'gas-phase synthetic chemistry' remains of current interest. Cycloaddition reactions involving ion-molecule reactions in the gas phase and comparison to reactions in solution are the subjects of a recent review [10].…”

Gas Phase Decarbonylation and Cyclization Reactions of Protonated N-Methyl-N-Phenylmethacrylamide and Its Derivatives Via an Amide Claisen Rearrangement

“…T andem mass spectrometry provides extensive structural information about organic molecules, and is an important tool for mechanistic studies in gas phase organic chemistry [1][2][3][4][5][6][7][8][9][10]. Information about the energetics of gas phase reactions and fragmentation pathways can be investigated by adjusting the collision energy, the timescale of dissociation, and the collision gas.…”

“…Recently, we reported many interesting gas phase reactions and related aromatic substitution rearrangement reactions, including benzyl migration [11], Cope rearrangement [11], Smiles rearrangement [12], metal cation catalyzed Smiles rearrangement [13,14], gas phase rearrangement of the p-aminophenylsulfonyl cation [15], sulfonyl-sulfinate rearrangement [16], retroMichael type fragmentation [17], and gas phase Favorskii rearrangement [18]. Certain analogies between reaction mechanisms in the gas phase and solution have been known for a long time [1][2][3][4][5][6][7][8][9][10]19]. The reactivities and behaviors of ionic species in the gas phase and in solution can be correlated [12,[20][21][22], and there is a significant association between gas phase reactions and the analogous reactions in solution.…”

ESI‐FTICRMS Characterization of the Intermediates in Cycloisomerization of Trifluoromethyl‐substituted Enynols through Changing the Protecting Group of Substrate

“…18,20,21 Though certain analogies between observations in the electrosprayed gas-phase intermediates and their existence in the solution-phase have been known for a long time, sometimes it is possible to establish organic reaction mechanism by extrapolating the findings from gas-phase chemistry to solution-phase chemistry. [21][22][23][24][25] In the previous work, we have used electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS) to study the mechanism of some palladium-catalyzed organic reactions, and have successfully characterized some key intermediates of the reactions, [26][27][28][29] which provided some evidence to confirm the proposed mechanism.…”