Date of Award
Doctor of Philosophy (PhD)
Dr. Johan K. Terlouw
Ionic and neutral hydrogen shift isomers of common nitrogen containing heterocycles, such as pyridine, have been generated and identified as stable species in the gas phase. The ionic isomers could be obtained by dissociative electron ionization of carefully chosen precursor molecules. Their structure characterization could be realized using tandem mass spectrometry based techniques. Not only conventional metastable ion (MI), collision-induced dissociation (CID) and neutralization-reionization (NR) techniques were used but also the novel hybrid techniques, CID/CID and NR/CID. The use of deuterium labelled isotopomers and quantum chemical calculations formed an essential component in the interpretation of the results. The neutral hydrogen shift isomers are ylides, carbenes or betaines. Such species are frequently invoked as key intermediates in synthetic and metabolic pathways but their high reactivity in bimolecular reactions often precludes their identification in condensed phases. However, in the dilute gas phase of the mass spectrometer, where intermolecular reactions do not occur, the structure and intrinsic stability of such species may be examined. The mass spectrometric technique of neutralization-reionization (NR) is ideally suited for this purpose. In this technique fast moving beams of structurally well characterized ions are neutralized by charge exchange. The structures of the resulting neutrals are then probed with subsequent collisional ionization experiments. The thermodynamic stability of the various ionic hydrogen shift isomers appeared to be comparable to that of the parent isomer of conventional structure. A case in point is the pyridine ion Ia·+ for which ΔHf = 247 kcal/mol and whose hydrogen shift isomers pyridine-2-ylidene·+ (IIa·+ ), pyridine-3-ylidene·+ (IIb ·+ ) and pyridine-4-ylidene·+ ( IIc·+ ) have enthalpies of formation of 245, 244 and 242 kcal/mol. CID mass spectrometry provided a convenient and reliable tool for the characterization of these ions. The (distonic) ions IIa ·+ and IIb·+ but not IIc·+ could be subjected to reduction by single electron transfer in NR experiments. Intense "survivor" signals were obtained but collision experiments of the reionized neutrals (NR/CID) were required to establish the carbene structure of the neutral species generated. The experimental results concur with predictions from quantum chemical calculations that the neutral (singlet and triplet) and ionic isomers are minima on the potential energy surfaces which are separated by substantial (1,2-H shift) isomerization barriers.* The same strategy was used to probe the structure and stability of the H-shift isomers of neutral and ionic pyrazine (Ib·+ ), pyrimidine (Ic·+ ), thiazole (IIIa·+ ) and imidazole (IIIb ·+ ). Among the elusive neutral species identified are the ylides pyrazine-2-ylidene, pyrimidine-2-ylidene, pyrimidine-4-ylidene, thiazol-2-ylidene, imidazol-2-ylidene and imidazol-4-ylidene and the betaine pyrazine-3-ylidene. Ab initio calculations on the potential energy surfaces confirm the experimental results but they also reveal that the pyrazine and pyrimidine systems feature additional isomers of comparable stabilities. The final component of this work deals with the decarbonylation reaction of ionized 2-acetylpyridine, 2-acetylpyrazine and 2-acetylthiazole. Multiple collision experiments were used to show that this reaction does not involve a methyl migration yielding the 2-methyl substituted heterocycle as proposed in the literature. The product ions generated are the 2-methylene heterocycles, ionized 2-methylene-1,2-dihydropyridine, 2-methylene-1,2-dihydropyrazine, and 2-methylene-2,3-dihydrothiazole, suggesting that the decarbonylation involves a 1,4-H shift followed by an ipso substitution. NR/CID mass spectrometry was used to establish that the neutral counterparts of the ionized decarbonylation products retain their structural integrity in the rarefied gas phase. *Please refer to dissertation for diagrams.
Lavorato, David J., "Hydrogen shift isomers of pyridine and other N-heterocycles: A tandem mass spectrometry study" (1999). Open Access Dissertations and Theses. Paper 1700.