Conformations, % axial substituted cyclohexanes

Energy differences between conformations of substituted cyclohexanes can be measured by several physical methods, as can the kinetics of the ring inversion processes. NMR spectroscopy has been especially valuable for both thermodynamic and kinetic studies. In NMR terminology, the transformation of an equatorial substituent to axial and vice versa is called a site exchange process. Depending on the rate of the process, the difference between the chemical shifts of the nucleus at the two sites, and the field strength... 

Each carbon atom in cyclohexane is bonded to two hydrogen atoms, one directed upward and one downward. As the carbon atoms are numbered in Figure 3-22, Cl has an axial bond upward and an equatorial bond downward. C2 has an equatorial bond upward and an axial bond downward. The pattern alternates. The odd-numbered carbon atoms have axial bonds up and equatorial bonds down, like Cl. The even-numbered carbons have equatorial bonds up and axial bonds down, like C2. This pattern of alternating axial and equatorial bonds is helpful for predicting the conformations of substituted cyclohexanes, as we see in Sections 3-13 and 3-14. 

Q Draw accurate cyclohexane conformations, and predict the most stable conformations of substituted cyclohexanes. Explain why large groups are more stable in equatorial positions rather than in axial positions. Problems 3-43,44,45, and 49... 

The physical, chemical cind biological properties of a molecule often depend critically upo the three-dimensional structures, or conformations, that it can adopt. Conformational analysi is the study of the conformations of a molecule and their influence on its properties. Th development of modem conformational analysis is often attributed to D H R Bcirton, wh showed in 1950 that the reactivity of substituted cyclohexanes wcis influenced by th equatoricil or axial nature of the substituents [Beirton 1950]. An equcilly important reaso for the development of conformatiorml analysis at that time Wcis the introduction c analytic il techniques such as infreired spectroscopy, NMR and X-ray crystaillograph] which actucilly enabled the conformation to be determined. 

Conformational effects on 15N shifts in substituted cyclohexanes make an axial NH2 more shielded than an equatorial one. Also, 15N resonances are deshielded by ft substitution more extensively than are 13C resonances of cyclic hydrocarbons, but the magnitude of the effect depends on the degree of nitrogen substitution. Carbons in the y position shield the nitrogen in a manner analogous to 13C, but to a smaller extent in methanol than in cyclohexane solutions, and less for tertiary amines than for primary and secondary amines. These differences have been attributed in part to possible conformational influences on the stereoelectronic relationships between the lone pair and the C—C bonds. 

The conformational properties of mono-substituted cyclohexanes, C V, 1111X, in their thiourea inclusion compounds have been studied102. Variable-temperature MAS spectra demonstrate that a chair-chair ring inversion process occurs in the thiourea tunnel, in which the axial and equatorial conformers are interconverted. Predominance of the equatorial conformer is found when X = NH2. 

Since the adamantane ring system is composed of three interlocking cyclohexane rings, all in the perfect chair conformation, /3-sub stituted adamanta-nones are also ideal models for establishing quantitative substituent contributions to the optical rotatory dispersion of cyclohexanones in the undisturbed chair form. A variety of optically active /3-equatorial and /3-axial substituted adamantanones have been synthesized 18°-184) and their circular dichroism determined 184-185) jji generai) axial polar substituents (C02R, Cl,... 

The table shows the preference of a number of substituted cyclohexanes for the equatorially substituted conformer over the axially substituted conformer. 

More evidence comes from the reactions of substituted cyclohexanes. You saw in Chapter 18 that substituents on cyclohexanes can be parallel with one another only if they are both axial. An equatorial C-X bond is anti-periplanar only to C-C bonds and cannot take part in an elimination. For unsubstituted cyclohexyl halides treated with base, this is not a problem because, although the axial conformer is less stable, there is still a significant amount present (see the table on p. 462), and elimination can take place from this conformer. 

The introduction of a methyl group at C(6) of aminocyclohexenes causes a downfield shift of the resonance of this carbon ( + 2.7 ppm for compound 84) and an upfield shift of C(4) (— 4.6 ppm for 84). Comparison of these shifts with those corresponding to methyl-substituted cyclohexanes (equatorial a-Me group + 5.96 ppm axial a-Me 1.40 ppm equatorial y-Me + 0.05 ppm axial y-Me — 6.37 ppm)23 indicates that the methyl group is in preference in the pseudoaxial disposition 84a, than in 84e as shown below15. This conformation is free from allylic 1,2-strain (A1,2) and had been proposed24 on the basis of reactivity studies. 

Until recently knowledge of twist conformation of simple cyclohexanes could be said to be limited to certain di-f-butylcyclohexanes which if they existed as chair conformations would have an axial f-butyl group, to cyclohexane-1,4-dione and to certain highly substituted cyclohexanes. Undoubtedly twist conformations are quite common, it is unfortunate that reasonably direct evidence is often not available. 

On each carbon, one bond is directed up or down and the other more or less in the plane of the ring. The up or down bonds are called axial and the others equatorial. The axial bonds point alternately up and down. If a molecule were frozen into a chair form, there would be isomerism in mono-substituted cyclohexanes. For example, there would be an equatorial methylcyclohexane and an axial isomer. However, it has never been possible to isolate isomers of this type at room temperature. This proves the transient existence of the boat or twist form, since in order for the two types of methylcyclohexane to be nonseparable, there must be rapid interconversion of one chair form to another (in which aU axial bonds become equatorial and vice versa) and this is possible only through a boat or twist conformation. Conversion of one chair form to another requires an activation energy of lOkcalmoP (42kJmol ) and is very rapid at room temperature. However, by working at low temperatures, Jensen and Bushweller were able to obtain the pure equatorial conformers of chlorocyclohexane and trideuteriomethoxycyclo-hexane as solids and in solution. Equatorial chlorocyclohexane has a half-life of 22 years in solution at — 160°C. 

Substrate and/or intermediate species absorb on an electrode surface and orient themselves so that their least hindered sides face the electrode unless there is another effect, such as a polar one. This may be the simplest steric factor governing the stereochemistry of reactions. There may also be more complicated steric effects that result in conformational or configurational change of the species, since the electrode on which the species adsorb strongly may behave as if it were a very bulky substituent. For example, visualize a substituted cyclohexane molecule (Fig. 1). The substituent must be preferentially in the equatorial position in a free state (I), but it may be in the axial position in an adsorbed state (II), if the electrode effectively gives more steric hindrance than the substituent. 

The chair conformation of cyclohexane has many chemical consequences. For example, we ll see in Section 11.12 that the chemical behavior of many substituted cyclohexanes is directly controlled by their conformation. Another consequence of the chair conformation is that there are two kinds of positions for substituents on the ring axial positions and equatorial... 

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