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

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 pKa values of protonated compounds that varied from 2.8 to 4.3 (in d4‐methanol) depending on the structure of the azaarylsulfanyl group. The trans‐2‐(azaarylsulfanyl)‐cyclohexanol moiety can be used as a conformational trigger for the control of the geometry‐dependent molecular properties via pH‐induced switching of the preferred molecular conformation.