Chair conformations disubstituted cyclohexanes

If a disubstituted cyclohexane has two different substituents then the most stable conformation is the chair that has the larger substituent m an equatorial orientation This IS most apparent when one of the substituents is a bulky group such as tert butyl Thus the most stable conformation of cis 1 tert butyl 2 methylcyclohexane has an equatorial tert butyl group and an axial methyl group... 

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. 

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. 

Problem-Solving Strategy Drawing Chair Conformations 116 3-14 Conformations of Monosubstituted Cyclohexanes 117 3-15 Conformations of Disubstituted Cyclohexanes 120... 

Some students find it difficult to look at a chair conformation and tell whether a disubstituted cyclohexane is the cis isomer or the trans isomer. In the following drawing, the two methyl groups appear to be oriented in similar directions. They are actually trans but are often mistaken for cis. 

The chair conformer of cis-1,4-disubstituted cyclohexane has one substituent equatorial, the other axial. This will not necessarily be the case for other substitution patterns for example, the chair conformer of a cis-1,3-disubs tituted cyclohexane has either both substituents axial or both equatorial. Remember, the raV and trans prefixes merely indicate that both groups are on the same side of the cyclohexane ring. Whether the substituents are both axial/equatorial or one axial and the other equatorial depends on the substitution pattern. Each time you meet a molecule, draw the conformation or make a model to find out which bonds are axial and equatorial. 

The chair form of a diaxially 1,4-disubstituted cyclohexane with two identical substituents is shown in 17. This pair of conformers is defined as trans from either 17 or 18, as follows. From 17 insert an imaginary C(l)--C(4) bond and it is readily seen that the dihedral angle Cct-C(l)-"C(4)-C(3 is 180°, in accord with a trans configuration. 

In a monosubstituted cyclohexane, the substituent can be either in an equatorial or axial position. Equatorial positions are more spacious and in substituted cyclohexanes they are preferred. Cyclohexane rings flip between chair forms and establish an equilibrium. In the process of flipping, all equatorial positions become axial and all axial positions become equatorial. The equilibrium favors the chair in which substituents are equatorial. In monosubstituted cyclohexanes, the conformation in which the substituent is equatorial is favored. In disubstituted cyclohexanes where one group is axial and one equatorial, the equilibrium favors the chair form where the larger group occupies the more spacious equatorial position. 

Consider tmns-1,2-di methylcyclohexane 6. In the conformer 6a, the two equatorial methyl groups are gauche to each other, which will raise the energy by 0.9 kcal mol-1. In the conformer 6b, the product of chair inversion of 6a, each axial methyl group is engaged in two butane gauche interactions. This will raise the energy by 2 x (2 x 0.9) = 3.6 kcal mol-1. The conformer 6a, therefore, is more stable than 6b by 3.6 - 0.9 = 2.7 kcal mol-1. Thus, trans- 1,2-disubstituted cyclohexane must prefer the conformer in which both the substituents occupy equatorial positions. 

In 5,6 -type rearrangements of conformationally locked 1-cyclohexene derivatives, the stereochemical outcome depends on the substitution pattern at C-1. Axial attack leading to cis-1,4-disubstituted cyclohexane derivatives 4, 5. 6. and 8 via a chair transformation state is clearly preferred with substrates having a terminal CH2 group644. 

For each of the following disubstituted cyclohexanes, indicate whether the substituents in the two chair conformers would be both equatorial in one chair conformer and both axial in the other or one equatorial and one axial in each of the chair conformers ... 

When two cyclohexane rings are fused together, the second ring can be considered to be a pair of substituents bonded to the first ring. As with any disubstituted cyclohexane, the two substituents can be either cis or trans. If the cyclohexane rings are drawn in their chair conformations, the trans isomer (with one substituent bond pointing upward and the other downward) will have both substituents in the equatorial... 

The A value, the free-energy difference between the two chair conformations with axial and equatorial alkyl groups, is widely used as a measure of steric size . For all alkyl groups there is less than 7% of the axial conformation present at ambient temperature and direct quantitative observation of the equilibrium is not possible. Historically, indirect examination of conformational equilibria in disubstituted cyclohexanes has been used to predict equilibria in monoalkyl compounds (assuming additivity of substituent effects), and reviews of early work in this field and of the pitfalls encountered have been given... 

Trans 1,4-Disubstituted Cyclohexanes If we consider dimethylcyclohexanes, the structures are somewhat more complex because the cyclohexane ring is not planar. Beginning with rr<2 r-l,4-dimethylcyclohexane, because it is easiest to visualize, we find there are two possible chair conformations (Fig. 4.22). In one conformation both methyl groups are axial in the other both are equatorial. The diequatorial conformation is, as we would expect it to be, the more stable conformation, and it represents the structure of at least 99% of the molecules at equilibrium. 

Cis 1,4-DisubStituted Cyclohexanes cM-l,4-Dimethylcyclohexane exists in two equivalent chair conformations (Fig. 4.23). In a cis 1,4-disubstituted cyclohexane, one group is axial and the other is equatorial in both of the possible chair conformations. 

Cis 1,2-DiSUbStituted Cyclohexanes r-l,2-Dimethylcyclohexane has one methyl group that is axial and one methyl group that is equatorial in each of its chair conformations, thus its two conformations are of equal stability. 

Disubstituted cyclohexane derivatives present a more complex system because there are two chair conformations as well as other conformations. For all comparisons of enantiomers and diastereomers of cyclohexane derivatives, assume that the chair conformation is the only one of interest (see Chapter 8, Section 8.5.4). Even with this simplifying assumption, both chair conformations must be examined for each diastereomer. An example is 1,2-dimethyl-cyclohexane, which has a cis-diastereomer (G3) and a trans-diastereomer (G4A-G4E). It appears that G3 has a plane of symmetry by simply looking at the planar structure, and this is correct. In other words, G3 is a meso compound. However, G4A is labeled as having no symmetry, which indicates it should be a mixture of enantiomers. Is this correct One enantiomer of trans-diastereomer G4A [(li ,2 S)-dimethyIcycIohexane] has two chair conformations G4B and G4C. There is one axial and one equatorial methyl group in each chair conformation, and in the flat representation (G4A) a line is drawn between the methyl groups that suggests that the structure should be examined for the presence of a plane of symmetry. 

Cyclohexane derivatives exist in chair conformations. However, when evaluating disubstituted cyclohexane derivatives for symmetry it is helpful to analyze structures drawn flat. As an example of a disubstituted cyclohexane, let us consider the meth-ylcydohexanols. 4-Methylcyclohexanol has two stereocenters, but they are not chiral centers because the carbons of the stereocenters do not have four different groups attached. 4-Methylcyclohexanol therefore exisfs as two diastereomers, a pair of cis, trans isomers. Both of these isomers are achiral. In each, a plane of symmetry runs through the —CHj and —OH groups and the carbons bonded to them. 

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