The Hydrogen-Bond Basicity pKHB Scale of Peroxides and Ethers

Abstract

Using 4‐fluorophenol as a reference hydrogen‐bond donor, equilibrium constants, Kf, for the formation of 1:1 hydrogen‐bonded complexes have been obtained by FTIR spectrometry for 39 ethers of widely different structure (cyclic and acyclic ethers, crown ethers, glymes, acetals, orthoesters, and disiloxane) and 3 peroxides, in CCl4 at 298 K. The pKHB scale of monoethers extends from 1.44 for 2,3‐diadamant‐2‐yloxirane to –0.53 for hexamethyldisiloxane. The main effects explaining the variation of the hydrogen‐bond basicity of sp3 oxygen atoms are (i) the electron‐withdrawing field‐inductive effect [e.g. in (CF3)2CHOMe], (ii) the electron‐withdrawing resonance effect (e.g. in EtOCH=CH2) (iii) the steric effect (e.g. in tBu2O), (iv) the lone‐pair–lone‐pair repulsion (e.g. in cyclic peroxides), and (v) the cyclization giving the basicity order: oxetane > tetrahydrofuran > tetrahydropyran > oxirane. A spectroscopic scale of hydrogen‐bond basicity is constructed from the infrared frequency shift Δν(OH) of methanol hydrogen‐bonded to peroxides and ethers. The thermodynamic pKHB scale does not correlate with the ν(OH) scale because of (i) statistical effects in polyethers and peroxides (ii) secondary hydrogen‐bond acceptor sites (e.g. in benzyl ether), (iii) variations of the s character of oxygen lone pairs either by conjugation or cyclization, (iv) steric effects, (v) lone‐pair–lone‐pair repulsions, and (vi) anomeric effects. The ν(OH···O) band shape reveals two stereoisomeric complexes, the most stable being tetrahedral at the ether oxygen atom.

Discovery of Balovaptan, a Vasopressin 1a Receptor Antagonist for the Treatment of Autism Spectrum Disorder

“…By comparison with alkyl aryl ethers, dialkyl ethers are significantly better H-bond acceptors. 32,34 In line with this, 40 and 41 had slightly increased efflux ratios compared to the aryl ethers, yet well predicted by their log D using model 1.…”

Thermal and Volumetric Properties of Five Lactones at Infinite Dilution in Water

“…16,25,26 We alone could observe the water−lactone hydrogen bonding through visualized MD simulations using the simple didactic software Odyssey. 27 The simulations showed, in accord with previous findings from QM calculations, 25 that although water binds to both oxygen atoms of the lactone group, the protonation preferentially takes place at the carbonyl oxygen. Some structural effects, namely those of alkyl substitution, ring enlargement, and introduction of the double bond, on the studied dissolution properties of the aqueous lactones can be traced by comparing the respective data in Table 4.…”

Hydration of Aprotic Donor Solvents Studied by Means of FTIR Spectroscopy

“…It reveals that starting from the donor number value characteristic for monomeric water (DN = 18), solutes having stronger electron donating ability do not change HDO band position considerably and thereby do not change corresponding intermolecular distances of hydrated water. Qualitatively the same effect can be obtained by correlating R OO vs p K HB values, − instead of DN ones. p K HB , as the thermodynamic measure of hydrogen-bond basicity, should be by definition even more closely related to hydration effects.…”