Cyclohexane, monosubstituted

A monosubstituted cyclohexane, e.g. methylcyclohexane, exists theoretically in two isomeric forms with a chair-form ring, and the methyl substituent either axial or equatorial. Since these rapidly interconverl through a CH3... 

Conformational inversion (ring flipping) is rapid in cyclohexane and causes all axial bonds to become equatorial and vice versa As a result a monosubstituted derivative of cyclohexane adopts the chair conforma tion in which the substituent is equatorial (see next section) No bonds are made or broken in this process... 

The consequences of this point aie developed for a number of monosubstituted cyclohexane derivatives in the following section, beginning with methylcyclohexane. 

For the equilibrium between the axial and equatorial conformations of a monosubstituted cyclohexane. 

A substituent is less crowded and more stable when it is equatorial than when it is axial on a cyclohexane ring. Ring flipping of a monosubstituted cyclohexane allows the substituent to become equatorial. 

The chemical shifts of monosubstituted thiophenes relative to the a- and )8-hydrogens of thiophene at infinite dilution in cyclohexane are given in Table I and are discussed in the following. 

Because chair cyclohexane has two kinds of positions, axial and equatorial, we might expect to find two isomeric forms of a monosubstituted cyclohexane. In fact, we don t. There is only one methylcyclohexane, one bromocydohexane, one cycJohexanol (hydroxycyclohexane), and so on, because cyclohexane rings are confbnnationally mobile at room temperature. Different chair conformations readily interconvert, exchanging axial and equatorial positions. This interconversion, usually called a ring-flip, is shown in Figure 4.11. 

Even though cyclohexane rings rapidly flip between chair conformations at room temperature, the two conformations of a monosubstituted cyclohexane aren t equally stable. In methylcyclohexane, for instance, the equatorial conformation is more stable than the axial conformation by 7.6 kj/mol (1.8 kcal/mol). The same is true of other monosubstituted cyclohexanes a substituent is almost always more stable in an equatorial position than in an axial position. 

Monosubstituted cyclohexanes are more stable with their substituent in an equatorial position, but the situation in disubstituted cyclohexanes is more complex because the steric effects of both substituents must be taken into account. All steric interactions in both possible chair conformations must be analyzed before deciding which conformation is favored. 

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 (a) and the others equatorial (e). The axial bonds point alternately up and down. If a molecule were frozen into a chair form, there would be isomerism in monosubstituted cyclohexanes. For example, there would be an equatorial methylcyclohexane and an axial... 

Since in chair form, the bonds are axial or equatorial, therefore monosubstituted cyclohexane exists in two isomeric forms-the axial or equatorial. So while considering a reaction with a monosubstituted cyclohexane, one must consider the reaction of both the species, just as while writing... 

Such interconversions with monosubstituted cyclohexanes and also with disubstituted ones do not involve any rearrangement i.e., no chemical bonds are broken nor reformed, only their conformation changes and this has been confirmed by NMR studies e.g., methyl cyclohexane at -110°C gives separate signals for equatorially or axially oriented methyl groups. 

In a completely different interpretation Zefirov (242) proposed a new concept of frontier-orbital mixing (243) to explain how conformational and electronic effects in monosubstituted cyclohexanes are transmitted to remote 8-carbon atoms (Scheme 36). The orbitals at C(l) and C(4) in 112 are considered to be equatorial (242). A perturbation at C(l) (H is replaced by X) produces an electron-density shift from H(4) toward C(4) (242), which is associated with an upheld shift of the latter s signal. Although this approach appears to be quite crude and does not account for axial substituents, it deserves fiirther attention. 

Although analysis of the consequences of ring flip in a monosubstituted cyclohexane is pretty straightforward, the presence of two or more substituents requires careful consideration to decide which conformer, if any, is the more favoured. Let us illustrate the approach using 1,4-dimethylcyclohexane. Now, two configurational isomers of this structure can exist, namely trans and... 

In the trans isomer, one methyl is written down (dotted bond) whilst the other is written up (wedged bond). If we transform this to a chair conformation, as shown in the left-hand structure, the down methyl will be equatorial and the up methyl will also be equatorial. With ring flip, both of these substituents then become axial as in the right-hand conformer. From what we have learned about monosubstituted cyclohexanes, it is now easily predicted that the diequatorial conformer will be very much favoured over the diaxial conformer. 

Hence A (fra .s) = 4117.24kcal/mol for fra .s-l,4-di- -butylcyclohexane and A /(m) = 4113.72kcal/mol for the cis form. These two results are indicative of ring conformation since cA-l,4-di-t-butylcyclohexane is undoubtedly in a twist-boat form while the other is in chair conformation. The spectra of t-butylcyclohexane (in chair conformation) and of rrani-l,4-di- -butylcyclohexane are indeed very similar, except, of course, for carbon 4, which is the same as carbon 1 in the disubstituted molecule, whereas it is similar to the unsubstimted carbons in the monosubstituted cyclohexane. 

Another example of the dynamic equilibrium is that owing to ring inversion in cyclohexane resulting in two isomers of the monosubstituted six-membered ring... 

Ring-flip in chair conformation of monosubstituted cyclohexane... 

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 monosubstituted 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.219 This proves the transient existence of the boat or twist form, since in order for the two types of methylcyclohexane to be non-separable, there must be rapid interconversion of one chair form to another (in which all 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 about 10 kcal/mol (42 kJ/mol)220 and is very rapid at room temperature.221 However, by... 

The six axial bonds are directed upward or downward from the plane of the ring, while the other six equatorial bonds are more within the plane. Conversion of one chair form into another converts all axial bonds into equatorial bonds and vice versa. In monosubstituted cyclohexanes, for electronic reasons, the more stable form is usually the one with the substituent in the equatorial position. If there is more than one substituent, the situation is more complicated since we have to consider more combinations of substituents which may interact. Often the more stable form is the one with more substituents in the equatorial positions. For example, in ct-1,2,3,4,5,6-hexachlorocyclohexane (see above) four chlorines are equatorial (aaeeee), and in the /Tisomer all substituents are equatorial. The structural arrangement of the /3-isomer also greatly inhibits degradation reactions [the steric arrangement of the chlorine atoms is unfavorable for dehydrochlorination (see Chapter 13) or reductive dechlorination see Bachmann et al. 1988]. 

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