Conformations and structures of desflurane and isoflurane

The geometric structure and conformational properties of the two inhalation anesthetics desflurane (2-difluoromethoxy-1,1,1,2-tetrafluoroethane, CF3–CHF–O–CHF2) and isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane, CF3–CHCl–O–CHF2) were studied by gas electron diffraction (GED) and quantumchemical calculations (HF/3-21G*, B3PW91/6-311G(2d) and MP2/6-311G(2d)). Both compounds exist in the gas phase as mixtures of two conformers. The predominant form (80(8)% in desflurane and 83(11)% in isoflurane) possesses near trans configuration of the C–C–O–C skeleton (φ(C–C–O–C) = −146(4)° in desflurane and −136(5)° in isoflurane) and trans orientation of the CHF2 group (C–H bond trans to O–C bond). In the minor conformer, the CHF2 group is oriented gauche. These conformational properties are discussed in terms of anomeric effects. According to the theoretical calculations four or five stable conformers exist and the types and relative energies depend on the computational method. However, the two structures which are predicted by all three methods to be lowest in energy correspond to the predominant and minor conformer observed in the GED experiments. The gas phase structures of the predominant form are in very close agreement with the crystal structures which have been reported previously.