Exploration of trans-2-(azaarylsulfanyl)-cyclohexanols as potential pH-triggered conformational switches

Article abstract of DOI:10.1002/poc.4068

A series of trans-2-(azaarylsulfanyl)-cyclohexanols, structurally similar to previously studied trans-2-aminocylohexanols, have been synthesized and explored as conformational pH triggers. ¹H NMR spectroscopy was used to estimate the position of the chair-chair conformational equilibrium and its acid-induced shift towards the conformer with the azaarylsulfanyl and hydroxy groups in equatorial positions due to an intramolecular hydrogen bond and electrostatic interactions. Such acid-induced transition may be used to control the geometry-dependent molecular properties. The ¹H NMR titration curves were used for estimation of the pK_a values of protonated compounds that varied from 2.8 to 4.3 (in d₄-methanol) depending on the structure of the azaarylsulfanyl group.