Chapter 3 Alkanes and Cycloalkanes: Conformations and cis-trans Stereoisomers 1

Conformational Analysis Conformations are different spatial arrangements of a molecule that are generated by rotation about single bonds. Conformational analysis is the study of how conformational factors affect the structure of a molecule and its properties. 4

Representing Conformations These are common ways to show conformations. 4

Newman Projections In Newman projections we sight down a C ⎯ C bond. The front carbon by a point and the back carbon by a circle. Each carbon has three other bonds that are placed symmetrically around it. The bonds on the back carbon are shown sticking out from the circle. 4

Newman Projections of Ethane Newman projections differ with respect to the rotation of the front and back carbon atoms relative to each other. The angles H-C-C-H angle is the torsional or dihedral angle. 4

An Important Point: The terms anti and gauche apply only to bonds (or groups) on adjacent carbons, and only to staggered conformations. 6

Relative Stability of Newman Projections The eclipsed conformation of ethane is the highest energy conformation. Repulsion between bonds destabilizes the eclipsed conformation. The staggered conformation is the most stable. Better electron delocalization stabilizes the staggered conformation. Conformations that are not staggered are said to have torsional strain. 4

Relative Stability of Ethane Conformations Ethane has infinite conformations corresponding to changes in the H-C-C-H torsional angle. Follow the “red” hydrogen atoms. eclipsed staggered 4

Relative Stability of Newman Projections At any instant, almost all of the molecules are in staggered conformations; hardly any are in eclipsed conformations. The difference between these two conformations is 12 kJ/mol. 4

Propane Conformations File Name: AAAKPLN0 Figure: 03_08.jpg Title: The Newman Projection of Propane Caption: Propane is shown here as a perspective drawing and as a Newman projection looking down one of the carbon-carbon bonds. Notes: Propane is shown here as a perspective drawing and as a Newman projection looking down the C1—C2 bond. Chapter 3

Propane Conformations File Name: AAAKPLO0 Figure: 03_09.jpg Title: Conformational Analysis of Propane Caption: Torsional energy of propane. When a bond of propane rotates, the torsional energy varies much like it does in ethane, but with 0.3 kcal/mol (1.2 kJ/mol) of additional torsional energy in the eclipsed conformation. Notes: Much like ethane the staggered conformations of propane is lower in energy than the eclipsed conformations. Since the methyl group occupies more space than a hydrogen, the torsional strain will be 0.3 kcal/mol higher for propane than for ethane. The staggered conformations of propane is lower in energy than the eclipsed conformations. Since the methyl group occupies more space than a hydrogen, the torsional strain will be 0.3 kcal/mol higher for propane than for ethane. Chapter 3

Conformations of Butane There are two different staggered conformations for butane. The anti conformation is the most stable and the gauche conformation is higher in energy because the larger CH3 groups are closer. This is called steric strain. 4

Strain in Newman Projections Torsional strain is the strain that results from eclipsed bonds. Steric hindrance results when two atoms are too close together. Also called van der Waals strain. Steric strain is the combination of both of these. 4

Newman Projections of Butane The eclipsed conformation with the CH3 groups eclipsed has the most steric strain and is the highest energy conformation. 4

Conformations of Higher Alkanes The lowest energy conformation of alkanes has all bonds staggered. With simple alkanes this has a zig-zag arrangement of carbon atoms. 4

The Shapes of Cycloalkanes: Planar or Nonplanar? 1

Stabilities of Cycloalkanes Five- and six-membered rings are the most common in nature. Carbons of cycloalkanes are sp3 hybridized and thus require an angle of 109.5º. When a cycloalkane carbon has an angle other than 109.5º, there will not be optimum overlap and the compound will have angle strain. Angle strain is sometimes called Baeyer strain in honor of Adolf von Baeyer, who first explained this phenomenon. Torsional strain arises when all the bonds are eclipsed. Chapter 3

• Torsional strain strain that results from eclipsed bonds Types of Strain • Torsional strain strain that results from eclipsed bonds • van der Waals strain (steric strain) strain that results from atoms being too close together • angle strain strain that results from distortion of bond angles from normal values 3

Angle strain in Cycloalkanes Tetrahedral carbons prefer bond angles of 109.5o and angle strain refers to the strain molecules have when this bond angle cannot be matched. Cyclopropane has the highest angle strain since its bond angles are about 60o. Other cycloalkanes try to minimize the angle strain and are therefore not planar. 2

Angle strain in Cycloalkanes Heat of combustion gives a way to measure the relative stability of cycloalkanes. The lowest heat of combustion per CH2 group corresponds to the most stable cycloalkane. 2

Cyclopropane Strong sp3-sp3 s-bonds cannot be formed because of 60o bond angle. The bonds are called bent bonds. 2

Cyclopropane There is also high torsional strain because the C-H bonds are all eclipsed. 2

Nonplanar Cyclobutane Cyclic compound with four carbons or more adopt nonplanar conformations to relieve ring strain. Cyclobutane adopts the folded conformation (“envelope”) to decrease the torsional strain caused by eclipsing hydrogens. File Name: AAAKPMI0 Figure: 03_17.jpg Title: Conformations of Cyclobutane Caption: The conformation of cyclobutane is slightly folded. Folding gives partial relief from the eclipsing of bonds, as shown in the Newman projection. Compare this actual structure with the hypothetical planar structure in Figure 3-14. Notes: Cyclic compound with 4 carbons or more adopt non-planar conformations to relieve ring strain. Cyclobutane adopts the folded conformation to decrease the torsional strain caused by eclipsing hydrogens. Chapter 3

Cyclopentane Planar cyclopentane has low angle strain since the natural bond angle is 108o. Torsional strain is significant because the C-H bonds are eclipsed. 26

Cyclopentane The envelope and half-chair conformations have similar lower energy and rapidly interconvert. They relieve some, but not all, torsional strain. 26

Conformations of Cyclohexane 5

Cyclohexane The most stable conformation of cyclohexane is known as the chair conformation. The side view shows the bonds across from each other are parallel. One end carbon (1) is up and the other (4) is down. Solid wedges show bonds projecting towards the viewer. 26

Cyclohexane The Newman projection shows that all bonds are staggered minimizing torsional strain. 26

Cyclohexane Other conformations include the skew boat. Most molecules are in the chair conformation and less than 5 molecules in 100,000 are in the skew boat conformation at any point in time at 25 oC. Therefore we concentrate on the chair conformation 26

Axial and Equatorial Bonds in Cyclohexane 11

Definitions The 12 hydrogens of cyclohexane can be divided into two groups: axial and equatorial. Equatorial hydrogens lie around the equator of the molecule. Axial hydrogens are directed alternately up and down. 12

Conformational Inversion in Cyclohexane 16

Ring Inversion There are two chair conformations of cyclohexane that rapidly interconvert. An axial group in the original chair conformation becomes equatorial in the ring-inverted form and vice versa. 12

Ring Inversion Ring inversion procedes through highest energy half-chair conformations and the twist boat and boat conformations. 12

Conformational Analysis of Monosubstituted Cyclohexanes 19

Methylcyclohexane Interconversion between the two chair conformations occurs rapidly and the methyl group is either equatorial or axial. The conformation with an equatorial methyl is favored. 20

Methylcyclohexane Van der Waals strain between the methyl and the axial hydrogen atoms on the same side of the molecule destabilize the conformation with an axial methyl. 20

Chair Inversion of Fluorocyclohexane Crowding is less pronounced with a "small" substituent such as fluorine so the difference in energy is lower than that observed for the methyl substitutent. 20

Chair Inversion of t-butylcyclohexane Crowding is more pronounced with a “larger" substituent such as the tertiary butyl group so the difference in energy is much higher than that observed for the methyl substitutent. 20

Disubstituted Cycloalkanes: cis-trans Stereoisomers 1

Definitions of Isomers Isomers are different compounds that have the same molecular formula. Constitutional isomers differ in connectivity. Stereoisomers have the same connectivity but a different arrangement of the atoms in space. 20

cis and trans Substituents A cycloalkane with two substituents on different carbons in the ring may have two orientations. If the substituents are on the same side of the ring we say they are cis to each other. If the substituents are on the opposite sides of the ring we say they are trans to each other. 20

Relative Energies of Stereoisomers The cis-stereoisomer is higher in energy due to van der Waals strain. The difference in energy is determined by measuring the heat of combustion. 20

Conformational Analysis of Disubstituted Cyclohexanes 7

1,4-Dimethylcyclohexane Stereoisomers H3C H H3C CH3 H CH3 cis trans 5219 kJ/mol 5212 kJ/mol less stable more stable Trans stereoisomer is more stable than cis, but methyl groups are too far apart to crowd each other. 8

Conformational analysis of cis-1,4-dimethylcyclohexane H3C H Conformational analysis of cis-1,4-dimethylcyclohexane CH3 Two equivalent conformations; each has one axial methyl group and one equatorial methyl group H CH3 H3C 10

Conformational analysis of trans-1,4-dimethylcyclohexane CH3 H3C H Conformational analysis of trans-1,4-dimethylcyclohexane Two conformations are not equivalent; most stable conformation has both methyl groups equatorial. H H3C CH3 10

1,2-Dimethylcyclohexane Stereoisomers CH3 H H3C cis trans 5223 kJ/mol 5217 kJ/mol less stable more stable Analogous to 1,4 in that trans is more stable than cis. 8

Conformational analysis of cis-1,2-dimethylcyclohexane CH3 H Conformational analysis of cis-1,2-dimethylcyclohexane Two equivalent conformations; each has one axial methyl group and one equatorial methyl group H CH3 10

Conformational analysis of trans-1,2-dimethylcyclohexane CH3 Conformational analysis of trans-1,2-dimethylcyclohexane H H3C H Two conformations are not equivalent; most stable conformation has both methyl groups equatorial. H CH3 H3C 10

1,3-Dimethylcyclohexane Stereoisomers CH3 H3C H CH3 H3C H H cis trans 5212 kJ/mol 5219 kJ/mol more stable less stable Unlike 1,2 and 1,4; cis-1,3 is more stable than trans. 8

Conformational analysis of cis-1,3-dimethylcyclohexane CH3 H3C H Conformational analysis of cis-1,3-dimethylcyclohexane Two conformations are not equivalent; most stable conformation has both methyl groups equatorial. H3C H CH3 10

Conformational analysis of trans-1,3-dimethylcyclohexane CH3 Conformational analysis of trans-1,3-dimethylcyclohexane H3C H H Two equivalent conformations; each has one axial and one equatorial methyl group. H3C H CH3 10

Table 3.2 Heats of Combustion of Isomeric Dimethylcyclohexanes Compound Orientation -H° (kJ/mol) cis-1,2-dimethyl ax-eq 5223 trans-1,2-dimethyl eq-eq 5217* cis-1,3-dimethyl eq-eq 5212* trans-1,3-dimethyl ax-eq 5219 cis-1,4-dimethyl ax-eq 5219 trans-1,4-dimethyl eq-eq 5212* *more stable stereoisomer of pair 19

Other Disubstituted Cyclohexanes With two different substituents the lowest conformation of a particular isomer will have the larger substituent in the equatorial position. Consider for example the two chair conformations of cis-1-tert-butyl-2-methylcyclohexane More stable 8

Cycloheptane and Larger Rings Most stable conformation minimizes total strain. This is more complicated than cyclohexane because there are many conformations. Furthermore several conformations may be of similar energy. 26

Polycyclic Ring Systems 2

Spirocyclic Systems Spirocyclic compounds have two rings with one common atom. Named as spiro[number.number]alkane. The alkane suffix corresponds to the number of carbons in the two rings. The numbers of carbons in each ring not including the common atom are given in increasing order. This is spiro[3.4]octane. 3

Bridged Compounds Two nonadjacent atoms common to two, or more, rings. Named as bicyclo[number.number.number]alkane. The parent alkane corresponds to the total number of carbons in the bicyclic skeleton. The numbers correspond to the number of carbon atoms between the bridgehead atoms in descending order. This is bicyclo[3.2.1]octane. 4

Fused Ring Compounds Compounds where two rings share a common side. Named as bridged bicyclic systems with one bridge with 0 carbons. cis-Bicyclo[4.4.0]decane 5

Steroids Steroids have a tetracyclic carbon skeleton with fused rings. 12

Heterocyclic Compounds Cyclic compounds that contains an atom other than carbon in the ring (these are called heteroatoms). Oxygen containing heterocycles: ethylene oxide and tetrahydrofuran 14

Heterocyclic Compounds Nitrogen containing heterocycles: pyrrolidine and piperidine 14