The Thiazole Ylide: A Frequently Invoked Intermediate Is a Stable Species in the Gas Phase

Abstract

The 1, 2-hydrogen shift isomers of neutral (singlet and triplet) thiazole (1) and its radical cation have been investigated by a combination of mass spectro-metric experiments and hybrid density functional theory calculations. The latter were used to probe the structures and stabilities of selected C3 H3 NS and C3 H3 NS(.+) isomers and transition state structures. Although 3H-thiazole-2-ylidene (2) is less stable than 1, by 31.5 kcalmol(-1) , it is expected to be capable of independent existence, since the 1, 2-hydrogen shift from carbon to nitrogen involves a very large energy barrier of 72.4 kcalmol(-1) . The other 1, 2-hydrogen shift reaction from C(2) leads not to the expected cyclic 1H-thiazole-2-ylidene structure (3), which is apparently unstable, but rather to the ring-opened species HSCHCHNC (4), which is 34.5 kcalmol(-1) higher in energy than 1. The barrier in this case is lower but still large (54.9 kcalmol(-1) ). The triplet ground states of 1, 2 and 4 are considerably destabilised (69.5, 63.2 and 58.7 kcalmol(-1) ) relative to their singlet states. Interestingly, in addition to 2(.+) and 4(.+) , the cyclic radical cation 3(.+) is predicted to be stable although it is substantially higher in energy than ionised thiazole 1(.+) (by 53.9 kcalmol(-1) ), whereas 2(.+) and 4(.+) are much closer in energy (only 10.2 and 27.0 kcalmol(-1) higher, respectively). Dissuading 2(.+) and 3(.+) from isomerising to 1(.+) are energy barriers of 52.6 and 15.3 kcalmol(-1) , respectively. Experimentally, dissociative ionisation of 2-acetylthiazole enabled the generation of 2(.+) , which could be differentiated from 1(.+) by collisional activation mass spectrometry. Reduction of the ylide ion 2(.+) in neutralisation-reionisation mass spectrometry experiments yielded the corresponding neutral molecule 2. This direct observation of a thiazolium ylide provides support for postulates of such species as discrete intermediates in a variety of biochemical transformations.

Heterocyclic Carbenes: Synthesis and Coordination Chemistry

“…Compound 32 was also detected by a combination of electron-ionization and neutralization-reionization mass spectrometry starting from 2-acetylthiazole. [122] Quantum chemical calculations confirm that compound 32 is less stable by 31.5 kcal mol À1 than 33. Nonetheless, the existence of 32 appears possible as a result of the high energy barrier (72.4 kcal mol À1 ) for the 1,2-hydrogen shift from nitrogen to carbon.…”

“…Nonetheless, the existence of 32 appears possible as a result of the high energy barrier (72.4 kcal mol À1 ) for the 1,2-hydrogen shift from nitrogen to carbon. [122] Geometric parameters calculated for 32 match equivalent parameters for 31.…”

Heterocyclische Carbene – Synthese und Koordinationschemie

“…Beim weiteren Bestrahlen oder beim Erwärmen auf 60 K tautomerisiert 32 zum Thiazol 33 . Verbindung 32 konnte ebenfalls durch Kombination von Elektronenionisations‐ und Neutralisations‐Reionisations‐Massenspektrometrie ausgehend von 2‐Acetylthiazol nachgewiesen werden 122. Quantenchemische Rechnungen belegen, dass 32 um 31.5 kcal mol −1 weniger stabil ist als 33 .…”

Tunneling Assists the 1,2‐Hydrogen Shift in N‐Heterocyclic Carbenes

“…This assessment is in agreement with the experimental observation that any attempt to isolate 4 a was unsuccessful and always led to the final product, 4 b . In fact, 4 a has been generated and detected only in the gas‐phase by mass spectrometry,23 and further corroborates our finding that a monomer of 4 a cannot form thiazole because the only available pathway for such a transformation proceeds through the intramolecular 1,2‐hydrogen shift reaction which has an extremely high barrier (42.5 kcal mol −1 at M06‐2X/6‐31+G(d,p) level of theory, see Table 1).…”