Structural characterization and regiochemical differentiation of α-cyanoethylindole isomers in the gas phase

Abstract

Mass spectrometry and tandem mass spectrometry techniques have been used to study the gas phase ion chemistry of isomeric ␣-cyanoethylindoles obtained by photochemical reactions. Both the fragmentation reactions occurring in the ion source, as well as metastable decompositions produced by the molecular and selected fragment ions, have allowed us to structurally characterize and differentiate each isomer from the others. The experiments, carried out also on deuterium labeled analogs, have shown the role exerted by the ␣-cyanoethyl substituent and by its position at the indolic ring on gas phase reactions that resulted to be distinctive and selective for each isomer. Ab initio theoretical calculations have been used to evaluate the stability and chemico-physical properties of different ion structures. The structural characterization and differentiation of heterocyclic isomers, and of indole derivatives in particular, is quite important as they can show different chemico-physical properties and activities. As the gas phase reactions occurring inside a mass spectrometer are strictly related to the structure of a compound, mass spectrometry (MS) and tandem mass spectrometry (MS/MS) are very powerful tools for isomeric characterization and differentiation. Their application in the field of heterocycles, and in particular in the characterization of the indole skeleton, has been successful [4 -12].In the frame of a research aimed at studying the gas phase ion chemistry of heterocycles [13][14][15][16], we wish to report here on a study devoted to the characterization and differentiation of a series of ␣-cyanoethyl-3-methylindoles 1-4 and a 3H-indole derivative 5 (Scheme 1) obtained by photochemical reactions [17].All these compounds have the same formula and molecular weight equal to 184 u. Compounds 1-4 are regio isomers, differing in the position of the ␣-cyanoethyl substituent on the heterocyclic system. They are also structural isomers of derivative 5 that has the 3H-indole ring. The characterization and differentiation of Compounds 1-5, together with the study of analogs labeled at different positions, are interesting not only to evaluate the effect of the position of the substituent and of the nature of the indole ring on the gas phase decomposition pathways, but also to ascertain whether isomerization processes eventually occur. Different mass spectrometry and tandem mass spectrometry techniques have been applied to the study of different ionic species produced in the gas phase by Isomers 1-5 and to evaluate their unimolecular reactivity. Metastable decompositions followed by the molecular ions and the most abundant fragment ions formed under electron ionisation have been selectively studied. The experimental approach is accompanied by theoretical ab initio molecular orbital calculations. ExperimentalCompounds 1-5 were synthesized by photochemical irradiation at ϭ 253.7 nm of 3-methylindole (Fluka, Milan, Italy) and an excess of acrylonitrile (Aldrich, Milan, Italy) in methanol as previously reported [17]. Deuter...

Differentiation of heterocyclic regioisomers: a combined tandem mass spectrometry and computational study of N‐acridin‐4‐ylbenzylamide and N‐acridin‐2‐yl‐benzylamide

“…Nonetheless, some positional isomers could still be distinguished based on the relative abundances of these product ions. Isomeric differentiation of heterocyclic systems has also been reported based on major11 or on minor12–15 ions in MS/MS spectra, arising from regiospecific reactions. Alternatively, the use of ion‐molecule reactions in the gas phase was shown to allow the direct mass spectrometric positional assignment of configurations within homologous series 16, 17…”

Hydration/elimination reactions of trapped protonated fluoroalkyl triazines

“…By continuing our research on gas-phase ion chemistry of organic molecules, 9 we wish to report here on the positive electrospray ionization (ESI) MS n n D 1-3 spectra, obtained inside an ion trap, of fluoroalkyl triazines 1-3 (Scheme 1) whose synthesis has been published recently. 10 ESI measurements have been carried out on a LCQ-DECA (ThermoFinnigan, San Jose, CA).…”

Gas phase behavior of radical cations of perfluoroalkyl‐1,2,4‐triazines: an experimental and theoretical study

“…In the frame of a research aimed at studying the gas-phase ion chemistry of heterocyclic molecules, [22,23] we wish to report here the gas-phase behavior of compounds 1-4 (Scheme 1) and of their deoxygenated derivatives. The study has been carried out by using an electron ionization (EI) source internal to a quadrupole ion trap.…”