7.4 DISUBSTITUTED CYCLOHEXANES - Sapling Learning

1 DISUBSTITUTED CYCLOHEXANES281(b) Estimate the energy difference between the gauche and anti conformations of a reason why the energy difference between conformations of ethylcyclohexane isabout the same as that for methylcyclohexane, even though the ethyl group is larger than amethyl CYCLOHEXANESA. Cis Trans Isomerism in DISUBSTITUTED CyclohexanesConsider a typical DISUBSTITUTED cyclohexane, one stereoisomer of this compound , both the chloro and methyl groups are in equatorial po-sitions. This compound is in rapid equilibrium with a conformational diastereomer in whichboth the chloro and methyl groups assume axial conformation (or the mixture of them) is called designation trans is used with cyclic compounds when two substituents have anup down that the up down relationship is unaffected by the chair interconversion.

2 ( )LLLLHHClCH3downupLClLHupdownLHH3C( )trans-1-chloro-2-methylcyclohexaneLLHCl LLHCH3 LClLHLHH3C`M% 12/8/08 12:13 PM Page 281282 chapter 7 cyclic COMPOUNDS. stereochemistry OF REACTIONSIn a different stereoisomer of 1-chloro-2-methylcyclohexane, the chloro and methyl groupsoccupy adjacent equatorial and axial compound , called cis-1-chloro-2-methylcyclohexane, is also a rapidly equilibrating mix-ture of conformational diastereomers. In a cis- DISUBSTITUTED cycloalkane, the substituents havean up up or a down down , the cis relationship is unaltered by the chair same definition of cis and trans substitution can be applied to substituent groups inother positions of a cyclohexane ring, as illustrated by Study Problem Problem structures of the two chair conformations of trans-1, a trans- DISUBSTITUTED cyclohexane, the two substituent groups have an up down re-lationship.

3 It doesn t matter which chair conformation is drawn first, because the chair intercon-version does not affect the trans relationship of the two methyl groups:Notice that when the substituents in a DISUBSTITUTED cyclohexane are on asymmetric car-bons, the designations cis and trans specify the relative stereochemical configurations of thetwo asymmetric carbons, but they say nothing about the absolute configurations of these car-bons. Thus, there are two enantiomers of of cis-1-chloro-2-methylcyclohexane(1S,2R)- 1-chloro-2-methylcyclohexane(1R,2S)-1-ch loro-2-methylcyclohexaneCH3 ClLLLLCH3Cl( )trans-1,3-dimethylcyclohexanedownLLCH3C H3 LLCH3upCH3( )downdowndowndownLClLHLH3 CLLLHHClLH3C( ) 12/8/08 12:13 PM Page DISUBSTITUTED CYCLOHEXANES283 When a ring contains more than two substituents, cis trans nomenclature is usually cum-bersome.

4 For such cases, other systems have been developed to designate relative configura-tion. (See Further Exploration ) For each of the following compounds, draw the two chair conformations that are in equilibrium.(a) cis-1,3-dimethylcyclohexane(b) For each of the compounds in Problem , draw a boat Conformational AnalysisDisubstituted CYCLOHEXANES , like monosubstituted CYCLOHEXANES , can be subjected to confor-mational analysis. The relative stability of the two chair conformations is determined by com-paring the 1,3-diaxial interactions (or gauche-butane interactions) in each conformation.

5 Suchan analysis is illustrated in Study Problem Problem the relative energies of the two chair conformations of trans-1, conformation is more stable?SolutionThe first step in solving any problem is to draw the structures of the species two chair conformations of trans-1,2-dimethylcyclohexane are as follows:ConformationAhas the greater number of axial groups and should therefore be the less stableconformation but by how much? ConformationAhas four 1,3-diaxial methyl hydrogeninteractions (show these!), which contribute kJ mol_1( kcal mol_1)to its energy.

6 What aboutB?YoumightbetemptedtosaythatBhas no unfavorable interactionsbecause it has no axial groups, but in factBdoes have onegauche-butane interaction the onebetween the two methyl groups themselves, which have a dihedral angle between them of 60 ,just as ingauche-butane. This interaction can be seen in a Newman projection of the bondbetween the carbons bearing the methyl groups:This gauche-butane interaction contributes kJ mol_1( kcal mol_1) to the energy of confor-mation B(Fig. , p. 54). The relative energy of the two conformations is the difference betweentheir methyl hydrogen interactions: kJ mol_1(or kcal mol_1).

7 The diaxial conformation Ais less stable by this amount of projection%M"HHCH3CH3gauche methyl groups"H"HLLCH3CH3 LLCH3CH3 BALCH3CH3 LFurther Exploration Ways ofDesignating 12/8/08 12:13 PM Page 283284 chapter 7 cyclic COMPOUNDS. stereochemistry OF REACTIONSWhen two groups on a substituted cyclohexane conflict in their preference for the equator-ial position, the preferred conformation can usually be predicted from the relative conforma-tional preferences of the two groups. Consider, for example, the chair interconversion of tert-butyl group is so large that its van der Waals repulsions control the conformationalequilibrium (see Eq.)

8 , p. 280). Hence, the chair conformation in which the tert-butyl groupassumes the equatorial position is overwhelmingly favored. The methyl group is thus forcedto take up the axial is so little of the conformation with an axial tert-butyl group that chemists say sometimes thatthe conformational equilibrium is locked. This statement is somewhat misleading because it im-plies that the two conformations are not at equilibrium. The equilibrium indeed occurs rapidly, butsimply contains very little of the conformation in which the tert-butyl group is the energy difference between the two chair conformations of trans-1, Calculate the energy difference between cis-1,4-dimethylcyclohexane and the more stableconformation of trans-1, Use of Planar Structures for cyclic CompoundsAlthough many cyclic compounds (such as cyclohexane and its derivatives)

9 Have nonplanarconformations, planar structures of these compounds can be used for situations in which con-formational issues are not important. In this notation, the structures of cyclic compounds arerepresented by planar polygons with the stereochemistry of substituents indicated by dashedor solid wedges. In this type of structure, imagine viewing the ring from above. If a substituentis up, the bond to it is represented by a solid wedge; if it is down, the bond to it is representedas a dashed wedge. In this convention, one enantiomer of trans-1,2-dimethylcyclohexane canbe drawn as follows:A planar structure for cis-1,2-dimethylcyclohexane can be drawn in either of two ways:( )CH3CH3`orcis-1,2-dimethylcyclohexaneLCH 3CH3 LCH3CH3`( )LCH3CH3CH3CH3`downupL( )LCCH3 LHLHL%H3 CCH3H3 CLCH3 LHLHLCLCH3H3CH3C(smaller)(larger) 12/8/08 12.

10 13 PM Page DISUBSTITUTED CYCLOHEXANES285 The two planar structures are derived, respectively, by viewing the ring from above or the two structures are equivalent can be further demonstrated by turning either one over:A planar structure does not convey any conformational information. That is, so long as allconformations are viewed from the same face of the ring, the chair interconversion does notinterchange wedges and dashed lines because it does not change the up or down relationshipof the ring Draw a planar structure for each of the following compounds using dashed or solid wedgesto show the stereochemistry of substituent groups.