Abstract:

Conformer-resolved gas-phase spectroscopy probes the intrinsic structures and dynamics of isolated molecules without perturbation by a surrounding medium. We investigated jet-cooled phenacetin (PA) using mass-selected resonant two-photon ionization (R2PI), ultraviolet–ultraviolet hole-burning (UV–UV HB), and infrared-dip (IR-dip) spectroscopy, combined with quantum-chemical calculations. The congested R2PI spectrum was resolved into contributions assigned to syn-PA, anti-PA, and an additional folded-ethoxy conformer. UV–UV HB spectroscopy distinguished fundamental and hot transitions associated with methyl internal rotation. The folded-ethoxy structure of this conformer is supported by its conformer-specific NH-stretching frequency, low-frequency vibronic structure, Franck–Condon simulations, and calculated electronic excitation energy, and its lower calculated energy relative to anti-PA(fe) favors assignment to syn-PA(fe). Although anti-PA(fe) is predicted to lie only 1.26 kJ mol⁻¹ above syn-PA(fe), it was not separately resolved under the present experimental conditions, consistent with weak intensity and spectral overlap. These results show that ethoxy-group folding expands the intrinsic conformational landscape of phenacetin and demonstrate how conformer-selective spectroscopy distinguishes closely related structures and internal-rotation dynamics in a flexible pharmaceutical molecule.