Seven Conformations of the Macrocycle Cyclododecanone Unveiled by Microwave Spectroscopy

Abstract

The physicochemical properties and reactivity of macrocycles are critically shaped by their conformations. In this work, we have identified seven conformations of the macrocyclic ketone cyclododecanone using chirped-pulse Fourier transform microwave spectroscopy in combination with ab initio and density functional theory calculations. Cyclododecanone is strongly biased towards adopting a square configuration of the heavy atom framework featuring three C–C bonds per side. The substitution and effective structures of this conformation have been determined through the observation of its 13C isotopologues. The minimisation of transannular interactions and, to a lesser extent, HCCH eclipsed configurations drive conformational preferences. Our results contribute to a better understanding of the intrinsic forces mediating structural choices in macrocycles.

Conformational Panorama of Cycloundecanone: A Rotational Spectroscopy Study

“…Conformers VIII and IX , among the least abundant ones, show one angle with larger values of 119.2° and 120.3°, respectively. Bond angles are similar to those of cyclooctanone and cyclododecanone and not expected to contribute significantly to energy differences between conformations . The dihedral angles of the most abundant conformer are, in their majority, very close to the ideal 60°, −60° (gauche), and 180° (anti).…”

“…Three conformers were observed for cyclooctanone 20 and seven for cyclododecanone. 21 Both cycloketones showed a very strong preference for the lowest-energy conformation, which was driven by the minimization of transannular interactions, and, to a smaller degree, HCCH eclipsed configurations. Here, we extend our conformational studies of cycloketones to 11-membered cycloundecanone (CU).…”

“…CU is expected to present several conformers in the gas phase, as observed for cyclooctanone 20 and cyclododecanone. 21 Our investigation, using CP-FTMW spectroscopy and computational calculations, sought to characterize its conformational landscape and address the following questions: Would the conformational behavior of CU be closer to that of cyclooctanone (another medium-size ring), or cyclododecanone (of similar size)? Would its conformational preferences be driven by the same intramolecular interactions?…”

“…To gain a better understanding of the conformational preferences of medium and large cycles, we have recently studied cyclooctanone and cyclododecanone by chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy. Three conformers were observed for cyclooctanone and seven for cyclododecanone .…”

“…To gain a better understanding of the conformational preferences of medium and large cycles, we have recently studied cyclooctanone and cyclododecanone by chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy. Three conformers were observed for cyclooctanone and seven for cyclododecanone . Both cycloketones showed a very strong preference for the lowest-energy conformation, which was driven by the minimization of transannular interactions, and, to a smaller degree, HCCH eclipsed configurations.…”