In a conventional Mannich reaction using piperidine, hydroxypiperidines, morpholine, and N‐methylpiperazine with usnic acid, a deacetylation was observed resulting in a substitution at C‐2, a loss of an acetyl group, and a Mannich base with a stabilized enol. The enol has a hydrogen bond to the nitrogen of the secondary amine. The structure was investigated by nuclear magnetic resonance and deuterium isotope effects on 13C chemical shifts as well as with density functional theory calculations to study the changed hydrogen bond pattern. It was found that the hydrogen bond involving the OH‐9 group in chloroform forms a strong hydrogen bond than in usnic acid itself and that this hydrogen bond becomes even stronger in the more polar solvent, dimethylsulfoxide. Tautomerism was observed in the Mannich base as demonstrated by deuterium isotope effects on chemical shifts. The position of the tautomeric equilibrium depends on the solvent, and the position of the equilibrium governs the strength of the OH‐9…O═C hydrogen bond.
Bibliographical noteImportant note from the Publisher regarding the attached document:
"This is the peer reviewed version of the following article: Nguyen HGT, Nguyen VN, Kamounah FS, Hansen PE. Structure of a new usnic acid derivative from a deacylating Mannich reaction: NMR studies supported by theoretical calculations of chemical shifts. Magn Reson Chem. 2018;56:1094–1100. https://doi.org/10.1002/mrc.4760, which has been published in final form at https://doi.org/10.1002/mrc.4760. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."
- Mannich base
- usnic acid
- DFT calculations
- isotope effects
Nguyen, H. G. T., Nguyen, V. N., Kamounah, F. S., & Hansen, P. E. (2018). Structure of a new usnic acid derivative from a deacylating Mannich reaction: NMR studies supported by theoretical calculations of chemical shifts. Magnetic Resonance in Chemistry, 56(11), 1094-1100. https://doi.org/10.1002/mrc.4760