0L F

(b) Estimate the energy difference between the gauche and anti conformations of 1-fluoropropane. H3C L CH2 L CH2 L F

7.5 Suggest a reason why the energy difference between conformations of ethylcyclohexane is about the same as that for methylcyclohexane, even though the ethyl group is larger than a methyl group.


A. Cis–Trans Isomerism in Disubstituted Cyclohexanes
Consider a typical disubstituted cyclohexane, 1-chloro-2-methylcyclohexane. MCl ` % CH3


In one stereoisomer of this compound, both the chloro and methyl groups are in equatorial positions. This compound is in rapid equilibrium with a conformational diastereomer in which both the chloro and methyl groups assume axial positions. H L L H3C H


Cl CH 3 L



Either conformation (or the mixture of them) is called trans-1-chloro-2-methylcyclohexane. The designation “trans” is used with cyclic compounds when two substituents have an up–down relationship.


Cl L CH3













up (7.9) down

Notice that the up–down relationship is unaffected by the chair interconversion.

Solution In a trans-disubstituted cyclohexane. The same definition of cis and trans substitution can be applied to substituent groups in other positions of a cyclohexane ring. L H L H3C LH Cl L H3C Cl LH (7.3-dimethylcyclohexane L L CH3 (7. the substituents have an up–up or a down–down relationship. because the chair interconversion does not affect the trans relationship of the two methyl groups: up L CH3 down CH3 CH3 trans-1. but they say nothing about the absolute configurations of these carbons. It doesn’t matter which chair conformation is drawn first.2S)-1-chloro-2-methylcyclohexane (1S.282 CHAPTER 7 • CYCLIC COMPOUNDS. there are two enantiomers of cis-1-chloro-2-methylcyclohexane. the chloro and methyl groups occupy adjacent equatorial and axial positions. the cis relationship is unaltered by the chair interconversion. STEREOCHEMISTRY OF REACTIONS In a different stereoisomer of 1-chloro-2-methylcyclohexane.12) Notice that when the substituents in a disubstituted cyclohexane are on asymmetric carbons. called cis-1-chloro-2-methylcyclohexane.2R)-1-chloro-2-methylcyclohexane enantiomers of cis-1-chloro-2-methylcyclohexane L CH3 .10) This compound.2 Draw structures of the two chair conformations of trans-1. as illustrated by Study Problem 7. down L L cis-1-chloro-2-methylcyclohexane H H3C LH L down down H3C L L L Cl Cl LH L (7. Study Problem 7.3-dimethylcyclohexane. the two substituent groups have an up–down relationship. In a cis-disubstituted cycloalkane. the designations cis and trans specify the relative stereochemical configurations of the two asymmetric carbons. Thus. L Cl L Cl L L CH3 (1R. is also a rapidly equilibrating mixture of conformational diastereomers.2.11) down Again.

7.3-dimethylcyclohexane (b) trans-1-ethyl-4-isopropylcyclohexane 7.1. Such an analysis is illustrated in Study Problem 7.7 = 2. draw the two chair conformations that are in equilibrium.2.) PROBLEMS 7.6 .0 kJ mol_1 (or 3. What about B? You might be tempted to say that B has no unfavorable interactions because it has no axial groups. Conformational Analysis Disubstituted cyclohexanes.7 For each of the compounds in Problem 7. Which conformation is more stable? Solution The first step in solving any problem is to draw the structures of the species involved. like monosubstituted cyclohexanes.4 DISUBSTITUTED CYCLOHEXANES 283 Other Ways of Designating Relative Configuration Further Exploration 7. The relative stability of the two chair conformations is determined by comparing the 1. 54). which have a dihedral angle between them of 60°.8 = 12.3-diaxial interactions (or gauche-butane interactions) in each conformation. draw a boat conformation.2-dimethylcyclohexane are as follows: L CH3 A CH3 CH3 L CH3 B L Conformation A has the greater number of axial groups and should therefore be the less stable conformation—but by how much? Conformation A has four 1.0.6. B. just as in gauche-butane. cis–trans nomenclature is usually cumbersome.7 kcal mol_1) to the energy of conformation B (Fig. (See Further Exploration 7. p. The two chair conformations of trans-1. Study Problem 7. can be subjected to conformational analysis. The diaxial conformation A is less stable by this amount of energy.2-dimethylcyclohexane.9 kcal mol_1). .6 kcal mol_1) to its energy.3-diaxial methyl–hydrogen interactions (show these!). other systems have been developed to designate relative configuration.6 For each of the following compounds. but in fact B does have one gauche-butane interaction—the one between the two methyl groups themselves. 2.3 Determine the relative energies of the two chair conformations of trans-1.5.8 kJ mol_1 (0. This interaction can be seen in a Newman projection of the bond between the carbons bearing the methyl groups: H " L H " H CH3 CH3 L CH3 " H L M %CH 3 gauche methyl groups Newman projection This gauche-butane interaction contributes 2. The relative energy of the two conformations is the difference between their methyl–hydrogen interactions: 14.1 When a ring contains more than two substituents. which contribute 4 X 3.9 = 3.8 .3.7 = 14. For such cases.8 kJ mol_1 (4 X 0. (a) cis-1.

The equilibrium indeed occurs rapidly. 7. the bond to it is represented as a dashed wedge. the preferred conformation can usually be predicted from the relative conformational preferences of the two groups. for example.2-dimethylcyclohexane can be drawn in either of two ways: L CH3 CH3 CH3 or (7. the structures of cyclic compounds are represented by planar polygons with the stereochemistry of substituents indicated by dashed or solid wedges. one enantiomer of trans-1. If a substituent is up. In this notation.2-dimethylcyclohexane .13) H3C H3C L CL CH3 H H (larger) CH3 (smaller) L H L L H3C H3C The tert-butyl group is so large that its van der Waals repulsions control the conformational equilibrium (see Eq. C. the bond to it is represented by a solid wedge.14) A planar structure for cis-1. but simply contains very little of the conformation in which the tert-butyl group is axial.7. In this convention. Consider.284 CHAPTER 7 • CYCLIC COMPOUNDS. planar structures of these compounds can be used for situations in which conformational issues are not important.4-dimethylcyclohexane and the more stable conformation of trans-1. The methyl group is thus forced to take up the axial position.15) ` ` L CH3 CH3 CH3 cis-1. STEREOCHEMISTRY OF REACTIONS When two groups on a substituted cyclohexane conflict in their preference for the equatorial position. imagine viewing the ring from above. 7. Hence. the chair interconversion of cis1-tert-butyl-4-methylcyclohexane.4-dimethylcyclohexane. if it is down.4-dimethylcyclohexane. Use of Planar Structures for Cyclic Compounds Although many cyclic compounds (such as cyclohexane and its derivatives) have nonplanar conformations.2-dimethylcyclohexane can be drawn as follows: L down CH3 CH L 3 ` up L C % CH3 CH3 CH3 (7.8 Calculate the energy difference between the two chair conformations of trans-1. the chair conformation in which the tert-butyl group assumes the equatorial position is overwhelmingly favored. In this type of structure. There is so little of the conformation with an axial tert-butyl group that chemists say sometimes that the conformational equilibrium is “locked. PROBLEMS 7.” This statement is somewhat misleading because it implies that the two conformations are not at equilibrium. L HL L CH3 (7.9 Calculate the energy difference between cis-1. 280). p.

That the two structures are equivalent can be further demonstrated by turning either one over: ` CH3 CH3 turn 180° ` CH3 CH3 (7. L Cl CH3 both: ` CH3 Cl (7.3-dimethylcyclohexane (b) trans-1. First. L mirror CH3 H3C L L CH3 noncongruent mirror images of cis-1.2R)-1-chloro-2-methylcyclopentane 7.2-dimethylcyclohexane L CH3 . The chirality of either conformation can be demonstrated by showing that its mirror image is noncongruent.2-dimethylcyclohexane. (a) cis-1.7. Stereochemical Consequences of the Chair Interconversion The chair interconversion has some interesting stereochemical consequences that can be illustrated with interconversion dimethylcyclohexanes. the chair interconversion does not interchange wedges and dashed lines because it does not change the up or down relationship of the ring substituents. by viewing the ring from above or below. consider cis-1.2S.17) L L Cl L CH3 PROBLEMS 7. so long as all conformations are viewed from the same face of the ring. That is.16) A planar structure does not convey any conformational information.10 Draw a planar structure for each of the following compounds using dashed or solid wedges to show the stereochemistry of substituent groups.3-dimethylcyclohexane (c) (1R. respectively.3R)-2-chloro-1-ethyl-3-methylcyclohexane (d) (1S.4 DISUBSTITUTED CYCLOHEXANES 285 The two planar structures are derived.11 Draw the more stable chair conformation for each of the following compounds: (a) CH3 (b) Cl Cl (c) CH3 ` ` Cl O 23 C(CH3)3 CH(CH3)2 D.

structures A and B may not look like enantiomers. 6. L CH3 L CH3 planes of symmetry In other words.10A).3-dimethylcyclohexane is achiral and optically inactive. they cannot be separated at ordinary temperatures. another molecule with two asymmetric carbons.2-dimethylcyclohexane is a mixture of conformational enantiomers (Sec.and cis-1. cis-1.1 Relating Cyclohexane Conformations is the same as H3C B H3C L L CH3 enantiomer of structure A L CH3 B L (7.2-dimethylcyclohexane is not optically active at ordinary temperatures.18) L H3C A H3C enantiomers From the way they are drawn. even though each conformation has two asymmetric carbons. each a diastereomer of the other. Cis-1. STEREOCHEMISTRY OF REACTIONS However.21) . Cis-1.3-dimethylcyclohexane have internal mirror planes (planes of symmetry). L L L CH3 CH3 CH3 L (7.2.20) CH3 (7. the chair interconversion converts one enantiomer into the other: L CH3 chair interconversion (7. neither conformation is chiral because each has an internal plane of symmetry.3-dimethylcyclohexane. but they are! You can see this by turning structure B 120° about a vertical axis: 120° STUDY GUIDE LINK 7.19) In other words. The planar structures of both cis-1. Consequently. both conformations are meso. Like any meso compound. is a mixture of conformational diastereomers: L L CH3 CH3 chair interconversion L CH3 diastereomers Yet.3-dimethylcyclohexane is thus a rapidly interconverting mixture of two different meso compounds.286 CHAPTER 7 • CYCLIC COMPOUNDS. Because these enantiomers are interconverted very rapidly. cis-1. cis-1.

The enantiomers of trans-1.2-dimethylcyclohexane ` CH3 CH3 plane of symmetry (7. neither conformation would be optically active because neither is chiral.21). Although it does not exhibit optical activity at ordinary temperatures. on the other hand. might be separated at a very low temperature.2-dimethylcyclohexane is a mixture of chiral (and enantiomeric) conformations in rapid equilibrium. The symmetry of the planar structures of cis-1. this plane corresponds to an actual plane of symmetry in either conformation of cis-1. because each conformation is chiral and has no symmetry plane. Cis-1. However. if a cyclic compound has asymmetric carbons.23) .3-dimethylcyclohexane (Eq. Cis-1. Although these.2-dimethylcyclohexane is chiral.2-dimethylcyclohexane.3-dimethylcyclohexane thus conceals a subtle difference between the two isomers. the compound cannot be isolated in optically active form at room temperature. is a mixture of meso conformations. In either case.3-dimethylcyclohexane.2-dimethylcyclohexane represent a different situation. mirror CH3 CH3 H3C H3C noncongruent mirror images enantiomers of trans-1. this is not a plane of symmetry in the case of cis-1. We can see from its planar structures that trans-1. though.3-dimethylcyclohexane As we’ve just seen. at a temperature so low that the rate of the chair interconversion would be negligible.22) cis-1. then. 7.4 DISUBSTITUTED CYCLOHEXANES 287 CH3 plane of symmetry CH3 cis-1.2-dimethylcyclohexane The chair interconversion converts each enantiomer into a conformational diastereomer: L enantiomers CH3 CH3 H3C L H3C L chair interconversion conformational diastereomers chair interconversion CH3 L CH3 enantiomers L L conformational diastereomers H3C H3C (7. each of which would be optically active. it could in principle be separated into enantiomers.and cis-1. Generally speaking.7. one of two things most be true: either the compound is a rapidly equilibrating mixture of conformational enantiomers.2. or the compound is meso. and if its planar structure has an internal mirror plane. too.

(b) Does trans-1.4-dimethylcyclohexane? (d) Is trans-1.5 CYCLOPENTANE. like cyclohexane.1 (p.12 Determine whether each of the following compounds can in principle be isolated in optically active form under ordinary conditions. exists in a puckered conformation. but the substituents adopt positions that minimize van der Waals repulsions with neighboring groups.3-dimethylcyclohexane (b) 1.13 (a) Does trans-1. This conformation undergoes very rapid conformational changes in which each carbon alternates as the “point” of the envelope. For example.2-dimethylcyclohexane is chiral. Because trans-1.14 What is the relationship of the two structures in each set? That is.4-dimethylcyclohexane chiral? 7. STEREOCHEMISTRY OF REACTIONS Thus. PROBLEMS 7. H " L equatorial axial CH3 " CH3 H (7. the methyl group assumes an equatorial position at the point of the envelope. enantiomers.4-dimethylcyclohexane have any stereocenters? If so. Substituted cyclopentanes also exist in envelope conformations. 269) show that cyclopentane has somewhat higher energy than cyclohexane. identify them.288 CHAPTER 7 • CYCLIC COMPOUNDS. which is also shown in Fig. 7. CYCLOBUTANE. Cyclopentane Cyclopentane. called the envelope conformation (Fig.10).1-dimethylcyclohexane (c) cis-1. 7. The heats of formation in Table 7.24) " . (a) trans-1. AND CYCLOPROPANE A. in methylcyclopentane.4-dimethylcyclohexane contain asymmetric carbons? If so. each of the two enantiomers of trans-1. (c) What is the stereochemical relationship of the two chair conformations of trans1. identify them. or diastereomers? (a) CH3 CH3 CH3 (b) CH3 ` ` ` ` Cl CH3 Cl CH3 (c) ` Cl Cl ` Cl Cl 7. The higher energy of cyclopentane is due mostly to eclipsing between hydrogen atoms.4-dimethylcyclohexane (d) cis-1-ethyl-3-methylcyclohexane 7. are they identical molecules. each enantiomer is capable of independent existence and can be isolated in optically active form.2-dimethylcyclohexane is a rapidly interconverting mixture of conformational diastereomers.10.