Characterization and differentiation of heterocyclic isomers. tandem mass spectrometry and molecular orbital calculations on 3-methylisoxazolo- and 2-methyloxazolopyridines

Abstract

Metastable mass-analyzed ion kinetic energy (MIKE) and collision-induced dissociation MIKE spectrometries have been applied to the study of all members of two classes of heteroaromatic isomers: 3-methylisoxazolo-and 2-methyloxazolopyridines. The study revealed that tandem mass spectrometry can characterize and differentiate the isomeric ion structures produced by these heterocycles. In particular, the MIKE spectra of both the molecular ions and abundant fragments formed by CO and CH3CN losses show characteristic differences that allow distinction among the isomers dependent on the position of the nitrogen atom in the pyridine ring, and distinction of isoxazole derivatives from oxazoles. The results indicate that the isomerization of the isoxazole moiety to oxazole-proposed for other analogous compounds-does not occur in these heterocyclic systems. The experimental work is supported by molecular orbital calculations both on neutral molecules and on molecular and fragment ions.

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

“…Differently from positional isomers that often produce similar°mass°spectra° [13],°Compounds°1-5 give°rise°to fragmentation reactions in the ion source that result to be distinctive and regiospecific depending on the position of the ␣-cyanoethyl substituent on the indolic ring. Most of the unimolecular reactions are the same for all the°isomers°(Figure°1°and°Table°1),°but°it°is°possible°to differentiate each member on the basis of significant differences in the relative abundances of the product ions.…”

“…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.…”

“…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].…”

Part 5—mass spectra and library entries of benz(is)oxazoles

“…Among di †erent analytical techniques, mass spectrometry is a very powerful tool for the unambiguous identiÐcation and assignment of the structure of an unknown compound. To help in this aim, some collections of electron ionization mass spectra have been compiled, and more and more sophisticated search algorithms have been proposed and implemented.2, 3 In the ambit of a general project aimed at characterizing and di †erentiating heterocyclic isomers,4,5 after having studied methyloxazolopyridines, 6 we recently started to investigate their benzo derivatives. Although these compounds are fairly common, each of them has been studied independently of the others and their behaviours in the gas phase have been not compared.…”

Application of self-ionization for enhancing stereochemical and positional effects from arylglycosides under electron ionization conditions in an ion trap mass spectrometer

“…Different chemicophysical methods, such as nuclear magnetic resonance, circular dichroism, X-ray crystallography, and other spectroscopic methods can give useful and complementary information. One of these methods is represented by mass spectrometry (MS) [1,2] that has found more and more applications in isomer characterization and differentiation [3,4], some of them developed in our research groups [5][6][7]. MS offers several advantages over other techniques: speed of analysis, high sensitivity at low picomol level, possibility to carry out gas phase reactions, etc.…”