Abstract

Several isotopomers of cyclooctanone were prepared by selective deuterium substitution. Intrinsic isotope effects on <TEX>$^{13}C$</TEX> NMR chemical shifts of these isotopomers were investigated systematically at low temperature. These istope effects were discussed in relation to the preferred boat-chair conformation of cyclooctanone. Deuterium isotope effects on NMR chemical shifts have been known for a long time. Especially in a conformationally mobile molecule, isotope perturbation could affect NMR signals through a combination of isotope effects on equilibria and intrinsic effects. The distinction between intrinsic and nonintrinsic effects is quite difficult at ambient temperature due to involvement of both equilibrium and intrinsic isotope effects. However if equilibria between possible conformers of cyclooctanone are slowed down enough on the NMR time scale by lowering temperature, it should be possible to measure intrinsic isotope shifts from the separated signals at low temperature. <TEX>$^{13}C$</TEX> NMR has been successfully utilized in the study on molecular conformation in solution when one deals with stable conformers or molecules were rapid interconversion occurs at ambient temperature. The study of dynamic processes in general requires analysis of spectra at several temperature. Anet et al. did <TEX>$^1H$</TEX> NMR study of cyclooctanone at low temperature to freeze out a stable conformation, but were not able initially to deduce which conformation was stable because of the complexity of alkyl region in the <TEX>$^1H$</TEX> NMR spectrum. They also reported the <TEX>$^1H$</TEX> and <TEX>$^{13}C$</TEX> NMR spectra of the <TEX>$C_9-C_{16}$</TEX> cycloalkanones with changing temperature from <TEX>$-80^{\circ}C$</TEX> to <TEX>$-170^{\circ}C$</TEX>, but they did not report a variable temperature <TEX>$^{13}C$</TEX> NMR study of cyclooctanone. For the analysis of the intrinsic isotope effect with relation to cylooctanone conformation, <TEX>$^{13}C$</TEX> NMR spectra are obtained in the present work at low temperatures (up to <TEX>$-150^{\circ}C$</TEX>) in order to find the chemical shifts at the temperature at which the dynamic process can be "frozen-out" on the NMR time scale and cyclooctanone can be observed as a stable conformation. Both the ring inversion and pseudorotational processes must be "frozen-out" in order to see separate resonances for all eight carbons in cyclooctanone. In contrast to <TEX>$^1H$</TEX> spectra, slowing down just the ring inversion process has no apparent effects on the <TEX>$^{13}C$</TEX> spectra because exchange of environments within the pairs of methylene carbons can still occur by the pseudorotational process. Several isotopomers of cyclooctanone were prepared by selective deuterium substitution (fig. 1) : complete deuterium labeling at C-2 and C-8 positions gave cyclooctanone-2, 2, 8, <TEX>$8-D_4$</TEX> : complete labeling at C-2 and C-7 positions afforded the 2, 2, 7, <TEX>$7-D_4$</TEX> isotopomer : di-deuteration at C-3 gave the 3, <TEX>$3-D_2$</TEX> isotopomer : mono-deuteration provided cyclooctanone-2-D, 4-D and 5-D isotopomers : and partial deuteration on the C-2 and C-8 position, with a chiral and difunctional case catalyst, gave the trans-2, <TEX>$8-D_2$</TEX> isotopomer. These isotopomer were investigated systematically in relation with cyclooctanone conformation and intrinsic isotope effects on <TEX>$^{13}C$</TEX> NMR chemical shifts at low temperature. The determination of the intrinsic effects could help in the analysis of the more complex effects at higher temperature. For quantitative analysis of intrinsic isotope effects, the <TEX>$^{13}C$</TEX> NMR spectrum has been obtained for a mixture of the labeled and unlabeled compounds because the signal separations are very small.