Cyclohexane derivatives 1.4- dimethylcyclohexanes

Incorporation of stereogenic centers into cyclic structures produces special stereochemical circumstances. Except in the case of cyclopropane, the lowest-eneigy conformation of the tings is not planar. Most cyclohexane derivatives adopt a chair conformation. For example, the two conformers of cis-l,2-dimethylcyclohexane are both chiral. However, the two conformers are enantiomeric so the conformational change leads to racemization. Because the barrier to this conformational change is low (lOkcal/mol), the two enantiomers arc rapidly interconverted. 

Let us apply the methods of conformational analysis to the stereochemistry of cyclohexane derivatives and, since we are already somewhat familiar with interactions of the methyl group let us use the dimethylcyclohexanes as our examples. 

Conformational analysis of cyclohexane derivatives containing several different substituents follows along the same lines as that of the dimethylcyclohexanes. We need to keep in mind that, of two groups, the larger one will tend to call the tune. Because of its very large 1,3-diaxial interactions (Problem 9.3, p. 301), the bulky /er/-butyl group is particularly prone to occupy an equatorial position. If—as is usually the case—other substituents are considerably smaller than tert-butyl, the molecule is virtually locked in a single conformation the one with an... 

Dimethylcyclohexane Type This type of monocyclic terpene hydrocarbon will be named systematically as derivatives of cyclohexane, cyclohexene, and cyclohexa-diene (IUPAC rules). 

The reader will recall the ca k] moT error bars associated with methylating ethylene, acetylene, ethane and propane, even though both the reactant and product hydrocarbons are among the thermochemically best understood of any ever studied. The reader will also recall discrepancies with measured as well as estimated enthalpies of vaporization. Furthermore, error bars associated with measurements of enthalpy of formation are often several kJ moT in magnitude, even for unstrained and therefore comparatively simple hydrocarbons. For example, while the error bars for the enthalpies of formation of cyclohexane and its monomethyl derivative are both under 1 kJmoT, the error bars for all seven of the dimethylcyclohexanes are between 1.7 and 1.9 kJ moT. Perhaps suggestive of considerable sloppiness or uncertainty in the measurements, studies of the enthalpies of many cyclopropanes and other strained species lack error bars. 

Beckmann rearrangement of cyclohexane-1,3-dione. Methyl (50, R = Me, R1 = H) and dimethyl 50 (R = R1 = Me) derivatives were also prepared from 5-methyl- and 5,5-dimethylcyclohexane-l,3-dione, respec-... 

The temperature-dependent NMR spectra of cyclohexane itself were investigated more than 25 years ago by NMR using several methods and solvents The barrier for chair-to-chair interconversion was determined to be 10.25 kcal mol Subsequently, simple alkyl-substituted derivatives were examined by NMR, for example methylcyclohexane and 1,2-dimethylcyclohexane (Figure 9). The chemical shifts observed in the low-temperature region are in line with the steric interactions and the conformational increments discussed in Section ILB.4. 

Most natural products having cyclohexane rings exhibit chair conformations, but a class of compoimds foimd in hops has been found to exhibit a (twist) boat conformation in one of four six-membered rings. The results of a molecular mechanics study indicated that cis,frans,ds-l,2-diisopropyl-3,4-dimethylcyclohexane is the smallest monocyclic cyclohexane that is expected to exhibit a twist boat as its lowest energy conformation. If a cis substituent at C4 of a f-butylcyclohexane derivative is very large, that substituent may not be axial because the cyclohexane may not be in the chair conformation. Noe and co-workers were able to detect both the twist boat and chair conformations (Figure 3.24) of cis-l,4-di-f-butylcyclohexane with low temperature C NMK. The twist boat was found to be more stable than the chair by 0.47 kcal/mol at 129 K. 

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