Nuclear magnetic resonance experiments on acetals. Part XXXIII. Conformational equilibria in some 4,4-gem-substituted cyclohexanone dimethyl acetals

Abstract

Thermodynamic parameters for the conformational equilibria of seven 4-methyl-4-R-I ,1 -dimethoxycyclohexanones (R = Et, Prn. Pr'. Bun, and But) were obtained from temperature-adapted shift values. It w a s assumed that bulkier alkyl groups will take the equatorial position rather than the methyl group. AAG" values are found to be larger than expected from the additivity principle, except for But where the contrary i s found. For all derivatives AAH' = ca. 485 cal mol-l. Unfavourable entropic contributions are found for axial a-branched substituents.SHIFTS for methoxy-groups are different when in either the axial or equatorial position,l allowing this group to be used as a possible probe for conformational studies. A systematic study of some cyclohexanone dimethyl acetals, substituted in the 3-and/or 4-position, and of some bicyclic derivatives, has shown,, however, that the interpolation of absolute shift values, as observed in conformational heterogeneous systems between those OMe Xa R' OMe & R2 OMe IIe Ie C.found in model ' compounds, gives unreliable results. Shift values of the methoxy-signals are influenced by substituents on C(3) and C(4), and attempts to predict this influence by comparison with suitable model compounds were unsuccessful. Thus, we attempted to predict the influence of the Me-4eq or Me-4ax group on the shift of the methoxy-group by comparison of Av in 1,1-dimethoxy-3-rnethylcyclohexane with Av in cis-1 ,ldimethoxy-3,5-dimethylcyclohexane. From this, a correction (0-92 in CS, and 0432 Hz in CDClJ might be introduced for the Av values observed in cis-and transl,l-dimethoxy-3,4-dimethylcyclohexane leading to Av(Me-4ax) (2.44 in CS, and 3.73 Hz in CDC13) and to Av(Me-4eq) (3.53 and 4-80 Hz). Finally from the value observed in 1,1-dimethoxy-4-rnethylcyclohexane (3.36 in CS, and 4-50 Hz in CDCl,) one would predict Ke(CS2) = (2.44 + 3-36)/(3.53 -3.36) = 33 [AG",,(Me) = 2-08 & 0.2 kcal mol-l] and Ke(CDC13) = (3.73 + 4-50)/(4.80 -4-50) = 27 [AGoW1(Me) = 1-96 & 0.13 kcal mol-l] and these values are certainly too high, the expected value being 1.69 kcal m0l-1.~94The absolute shift method definitely fails when trying to evaluate the position of equilibrium as a function of temperature. Thus it was found that even for anancomeric models Av, changes with temperature, the variation being of the same magnitude as that caused by the t

An improved preparation of .DELTA.8,9-octal-1-one

“…Chloro acetal 4 was prepared by the sequence used by Forbes,5 rather than by that employed by Johnson.6 Use of activated magnesium powder,7 as in Marfat and Helquist's work,4 facilitated preparation of Grignard reagent 3 from 4 under milcl conditions and helped to avoid the difficulties in working with 3 noted by Forbes. 5 Addition of an ethereal solution of 5 to 3 equiv of 38 in THF containing a solution of cuprous bromide-dimethyl sulfide complex in dimethyl sulfide9 at -78 °C led to formation of 6, which could be isolated chromatographically in ca. 80% crude yield.…”