Control over the Hydrogen-Bond Docking Site in Anisole by Ring Methylation

• Published in: Angewandte Chemie (International ed.) Vol. 55; no. 5; pp. 1921 - 1924
• Main Authors: Gottschalk, Hannes C., Altnöder, Jonas, Heger, Matthias, Suhm, Martin A.
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 26.01.2016; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Anisole; aromatic substitution; Chemical bonds; Chemical energy; dispersion control; Docking; Hydrogen; Hydrogen bonding; Hydrogen bonds; Infrared spectroscopy; Jets; Methanol; Methylation; molecular recognition; Quantum chemistry; Spectroscopic analysis; Structural stability; vibrational spectroscopy; molecular recognition; vibrational spectroscopy; aromatic substitution; hydrogen bonds; dispersion control
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201508481

The supramolecular docking of methanol to anisole may occur via an OH⋅⋅⋅O hydrogen bond or via an OH⋅⋅⋅π contact. The subtle balance between these two structures can be varied in supersonic jets by one order of magnitude through single to triple methylation of the aromatic ring and introduction of a single tert‐butyl substituent, as evidenced by infrared spectroscopy. This steep variation makes it possible to assess the accuracy of relative quantum‐chemical energy predictions on a kJ mol−1 level, promising insights into inductive, mesomeric, and dispersive effects. The zero‐point‐corrected B3LYP‐D3/aVTZ level is shown to provide an accurate relative description of the two very different hydrogen bonds, similar to a wavefunction‐based protocol including CCSD(T) corrections applied to the same structures. M06‐2X alone systematically overestimates the stability of π coordination. π or O? It's all in the balance! The alkylation pattern of anisole influences the preferred docking site for the OH group of a methanol solvent molecule—at the ether oxygen or the π system of the ring. Vibrational spectroscopy of molecular pairs at low temperature reveals the preferences of this intermolecular balance and provides kJ mol−1 quality ratings for quantum chemical predictions.