Hydrogen bonding and steric effects on rotamerization in 3,4-alkylenedioxy-, 3-alkoxy- and 3,4-dialkoxy-2-thienyldi(tert-butyl)methanols: an NMR, IR and X-ray crystallographic study

摘要

The equilibrium constant for the anti ↔ syn rotamerization (anti: intramolecularly hydrogen-bonded hydroxy group;nsyn: “free” hydroxy group) of 3,4-alkylenedioxy-, 3-alkoxy- and 3,4-dialkoxy-2-thienyldi(tert-butyl)methanolsndepends on the 3,4-alkylenedioxy or alkoxy group(s) and the solvent, hydrogen-bonding solvents such as DMSOnand pyridine favouring the syn isomer. Equilibrium constants ([syn]/[anti]) in chloroform and benzene decrease in thenorder: 3,4-OCH2O-, 3,4-O(CH2)2O-, 3-OMe, 3-OEt, 3,4-(OMe)2 ≈ 3-Oi-Pr, 3,4-(OEt)2, ranging over about 2.5 ordersnof magnitude. Variations in the IR OH stretching frequencies and the NMR OH proton shifts for the anti isomernindicate that intramolecular hydrogen bonding increases in roughly the same order. The syn anti rotation barriernin DMSO increases with substituent size and number. The 3,4-methylenedioxythienyl derivative has a rather lowernbarrier (17.5 kcal molnu00011n) than all the others (21.0–22.3 kcal molnu00011n). The syn anti rotation barrier is largelyndetermined by steric effects but intramolecular hydrogen bonding in the anti isomer contributes to the variationnof the anti syn rotation barrier. A single crystal X-ray diffraction study of the anti-3,4-diethoxy derivativenshows that the orientation of the 3-alkoxy group is very different from that in anti-3-methoxy-2-thienyldi-n(1-adamantyl)methanol. Molecular mechanics and quantum mechanical calculations are used in annattempt to rationalize the equilibrium data.