Effects of Chlorination on the Tautomeric Equilibrium of 2‐Hydroxypyridine: Experiment and Theory. Issue 15 (29th December 2016)

• Record Type: Journal Article
• Authors: Calabrese, Camilla; Maris, Assimo; Uriarte, Iciar; Cocinero, Emilio J.; Melandri, Sonia
• Is Part Of: Chemistry. Volume 23:Issue 15(2017)
• Page Start: 3595
• Page End: 3604
• Publication Date: 2016-12-29
• Subjects: conformation analysis -- rotational spectroscopy -- semiempirical calculations -- substituent effects -- tautomerism; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201604891
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The effects of halogenation on the tautomeric and conformational equilibria of the model system 2‐hydroxypyridine/2‐pyridone have been investigated through chlorine substitution at positions 3, 4, 5, and 6. In the gas phase, the lactim syn ‐periplanar tautomer (OHs ) was the predominant species for all compounds over the lactam form (C=O) and the less abundant anti ‐periplanar lactim (OHa ). However, the population of the three species was shown to be dependent on the position of the chlorine substitution. Chlorination in position 5 or 6 strongly stabilizes the OHs tautomer, whereas the C=O form has a significant population when the ring is chlorinated in positions 3 or 4. Overall, the OHa form is the least favourable form, although the 3‐substitution favours the population of this tautomer. In addition, the C=O tautomer is strongly stabilized in the solvent, which makes it the dominant form in some substituted species. This study has been performed by means of rotational spectroscopy in the gas phase and/or theoretical calculations in the isolated phase and in solution. Both the OHs and C=O forms of 5‐chloro‐2‐hydroxypyridine and the OHs form of 6‐chloro‐2‐hydroxypyridine were experimentally observed. All transitions displayed a complex nuclear hyperfine structure owing to the presence of the chlorine and nitrogen nuclei. For all species, a full quadrupolar hyperfine analysis has been performed. This has provided crucial information for the unambiguous identification of tautomers. Abstract : Out of balance ! Chlorination in different positions is shown to have a great influence on the conformational/tautomeric equilibrium of 2‐hydroxypriridine owing to inductive and mesomeric effects. The isomeric landscapes are explored and a semiempirical method to evaluate the halogenation effect is proposed.