Ketalization of phosphonium ions by 1,4-dioxane: Selective detection of the chemical warfare agent simulant DMMP in mixtures using ion/molecule reactions

Self Cite

The carbon-bonded gas-phase Meisenheimer complex of 2,4,6-trinitrotoluene (TNT) and the nitromethyl carbanion CH 2 NO 2 Ϫ (m/z 60) is generated for the first time by chemical ionization using nitromethane as the reagent gas. Collision-induced dissociation (CID) of the Meisenheimer complex furnishes deprotonated TNT, a result of the higher gas-phase acidity of TNT than nitromethane. The formation of Meisenheimer complexes with CH 2 NO 2 Ϫ in the gas phase is selective to highly electron-deficient compounds such as dinitrobenzene and trinitrobenzene and does not occur with organic molecules with lower electron-affinity such as methanol, methylamine, propionaldehyde, acetone, ethyl acetate, chloroform, toluene, m-methoxytoluene, and even nitrobenzene and p-fluoronitrobenzene. As such, the reaction allows selective detection of TNT in mixtures. Meisenheimer complexes between CH 2 NO 2 Ϫ and the three dinitrobenzene isomers display distinctive fragmentations. The oxygen-bonded -complex of TNT with the deprotonated hemiacetal anion CH 3 OCH 2 O Ϫ (m/z 61), represents a different type of Meisenheimer complex. It displays characteristic fragmentation involving loss of HNO 2 upon CID. The combination of a selective ion/molecule reaction (Meisenheimer complex formation) followed by a characteristic CID process provides a second novel and highly selective approach to the detection of TNT and closely related compounds in mixtures. The assay is readily implemented using neutral loss scans in a triple quadrupole mass spectrometer. Gas-phase reactions of denitrosylated TNT with benzaldehyde produce the corresponding dihydrofuran in an aldol condensation, a result that parallels the corresponding condensed-phase reaction. (J Am Soc Mass Spectrom 2004, 15, 998 -1004

Section: Discussionmentioning

confidence: 95%

“…Like Table 1. [19,20] can be adopted to detect these two unique transitions for TNT. As a demonstration, a mixture of ethyl isovalerate, 2,4-dimethyl-3-hexanone and TNT was ionized using the hemiacetal CH 3 OCH 2 OH as the reagent gas.…”

Section: Carbon-bonded Meisenheimer Complexesmentioning

confidence: 99%

Meisenheimer complexes bonded at carbon and at oxygen

Chen

Cooks

2004

Self Cite

“…Benzomorpholine, 3,4-dihydro-2H-1,4-benzoxazine, is a constituent of many naturally occurring substances [46]. An earlier study [51] from this laboratory reported that arenesulfenylium cation PhS ϩ can undergo the Eberlin reaction with 2,2-dimethyl-1,3-dioxolane, a cyclic ketal and form a characteristic four-membered cyclic product, 2-aryl-1,2-oxathietan-2-ium ion (the prototype Eberlin reaction [52][53][54][55] is the gas-phase transacetalization of acylium ions RCO ϩ by cyclic acetals or ketals, as shown in Scheme 7). It is therefore important to seek new simple routes for the synthesis of benzomorpholine.…”

Section: Synthesis Of N-heterocycles Using Arylnitrenium Ionsmentioning

confidence: 99%

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

Chen

Cooks

et al. 2004

Self Cite

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+*.

“…This results in three-to-fivemembered ring expansion to yield cyclic 1,3-dioxolanylium ions [21][22][23]. This structure-selective reaction, which displays many features common to those of transacetalization reactions of acylium ions with acetals and analogs [1], has been demonstrated to be very useful for both characterization and selective screening of specific compounds such as warfare agents [24].…”

mentioning

confidence: 99%

Gas-phase Meerwein reaction of epoxides with protonated acetonitrile generated by atmospheric pressure ionizations

Liu

Kord

2010

Ethylnitrilium ion can be generated by protonation of acetonitrile (when used as the LC-MS mobile phase) under the conditions of atmospheric pressure ionizations, including electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) as well as atmospheric pressure photoionization (APPI). Ethylnitrilium ion (CH 3 Ϫ C ϵ N ϩ H and its canonical form CH 3 Ϫ C ϩ ϭ NH) is shown to efficiently undergo the gas-phase Meerwein reaction with epoxides. This reaction proceeds by the initial formation of an oxonium ion followed by three-to-five-membered ring expansion via an intramolecular nucleophilic attack to yield the Meerwein reaction products. The density functional theory (DFT) calculations at the B3LYP/6-311ϩG(d,p) level show that the gas-phase Meerwein reaction is thermodynamically favorable. Collision-induced dissociation (CID) of the Meerwein reaction products yields the net oxygen-by-nitrogen replacement of epoxides with a characteristic mass shift of 1 Da, providing evidence for the cyclic nature of the gas-phase Meerwein reaction products. The gas-phase Meerwein reaction offers a novel and fast LC-MS approach for the direct analysis of epoxides that might be of genotoxic concern during drug development. Understanding and utilizing this unique gas-phase ion/molecule reaction, the sensitivity and selectivity for quantitation of epoxides can be enhanced. (J Am Soc Mass Spectrom 2010, 21, 1802-1813) © 2010 American Society for Mass Spectrometry G as-phase ion/molecule reactions are fast, efficient, and highly sensitive to the fine structural variations such as relative positions of functional groups. Their product distributions often provide diagnostic information for structural characterization of both reactant ions and neutral molecules [1][2][3][4]. Ion/ molecule reactions have also contributed significantly to the elucidation of organic reaction mechanisms, helping to bridge the gap between gas-phase ion chemistry and condensed-phase organic chemistry. It also provides access to key properties and intrinsic reactivities of a great variety of solvent-and counterion-free gaseous ions and, as such, constitutes a powerful tool for chemical studies. Many classic organic reactions have been studied in the gas phase using the mass spectrometric methods [5][6][7][8][9][10][11][12][13][14]. Recently, with the advent of electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), mass spectrometry has been widely used as an analytical tool for the study of atmospheric pressure ion/molecule reactions. These gas-phase reactions can even yield detailed information regarding the individual reaction step of the catalytic cycles, and thus allow the study of transient intermediates that have not been accessible previously by the condensed-phase techniques [15,16].Epoxides are common reagents or key intermediates in a wide variety of synthetically important condensedphase reactions, including asymmetric synthesis via the opening of the oxirane ring [17][18][19]. For example, Meerwein fi...