Competing inter- and intramolecular hydrogen bonding: solvent-driven rotamerization in 3,4-(ethylenedioxy)-2-thienyldi(tert-alkyl)methanols

Abstract

3,4-(Ethylenedioxy)-2-thienyldi(tert-alkyl)methanols exist in two rotameric forms, the equilibrium constant for the anti⇌syn rotamerization depending on the solvent. The equilibrium constant ([syn]/[anti]) is close to unity in benzene and chloroform, regardless of the tert-alkyl groups (tert-butyl or 1-adamantyl). This rises to about 10 in pyridine and 20 in DMSO (both at 25 °C), where intermolecular hydrogen bonding clearly prevails over intramolecular. For the di(tert-butyl) derivative there is a good correlation between the equilibrium constant (log K) and the hydrogen bond basicity parameter (β^H₂). The temperature dependence of the rotamer ratio in strongly hydrogen-bonding solvents indicates that the enthalpy term favours the syn isomer and the entropy term the anti. Rotation barriers have been measured in both hydrogen-bonding and non-hydrogen-bonding solvents. The differences in the equilibrium constants reflect the solvent effect upon the anti→syn isomerization, which is shown to be “solvent-driven” in the case of the di(1-adamantyl) derivative in pyridine.