1. Chapter 4: Lecture PowerPoint
Isomerism 1

2. 4.1 Isomerism: A Relationship
Two molecules are isomers of each other if they have the same molecular formula, but they are different in some way.
Their atoms can be connected in different ways; they can differ as a result of rotations about single bonds; or they can be mirror images of each other.

3. 4.2 Rotational Conformations, Newman Projections, and Dihedral Angles
A pair of conformational isomers, also called conformers, differ only by rotations about single bonds.
They are a type of stereoisomers.
Conformational isomers have the same connectivity, meaning that the same atoms in both species are bonded together by the same types of bonds.

4. Rotational Conformations
Rotational conformations describe molecules having different angles of rotation about single bonds.
Newman projections offer a convenient way to illustrate rotational conformations.

5. Dihedral Angles
Each angle of rotation defines a particular dihedral angle, Θ, corresponding to the angle between the C-X and C-Y bonds in the Newman projection.

6. 4.3 Conformational Isomers: Energy Changes and Conformational Analysis
Conformational analysis helps us better understand the nature of a rotation about a given bond.
Conformational analysis is a plot of a molecule’s energy as a function of that bond’s dihedral angle.

7. 4.3 Conformational Isomers: Energy Changes and Conformational Analysis continued…
Eclipsed conformations occur when the C-H (or C-R) bonds on the front carbon atom cover, or “eclipse,” those on the rear carbon atom in the Newman projections.
Staggered conformations occur when C-H (or C-R) bonds on the front carbon atom bisect those on the rear carbon atom.
The forms at the right from the left are: staggered, eclipsed, staggered, eclipsed, staggered, eclipsed, and finally staggered.

8. Torsional Strain
The difference in energy between a staggered conformation and an eclipsed conformation of H3C-CH3 is a result of torsional strain.
Torsional strain is an increase in energy (i.e., decrease in stability) that arises in an eclipsed conformation.
At room temperature, staggered conformations constantly interconvert through rotation about the C-C single bond.

9. Conformational Analysis of 1,2-Dibromoethane: Steric Strain, Gauche Conformations, and Anti Conformations
Steric strain is an increase in energy that results from electron repulsion between atoms or groups of atoms not bonded together.
If one H atom on each CH3 group in ethane (H3C-CH3) is replaced by another substituent, the energies of the three staggered conformations are no longer the same.

10. Gauche and Anti Conformation

11. Gauche and Anti Conformation continued…
Gauche conformation: Bulky groups are 60° apart in a Newman projection.
Anti conformation: Bulky groups are 180° apart in a Newman projection.

12. Longer Molecules and the Zig-Zag Conformation
For longer molecules, such as hexane, there are several single bonds about which rotation can occur.
This gives rise to many possible conformations.
Each of these bonds can exist in either a gauche or an anti conformation.
The most stable conformation of hexane is the all-anti conformation, sometimes called the zig-zag conformation.

13. 4.4 Conformational Isomers: Cyclic Alkanes and Ring Strain
Conformational analyses can also be applied to ring structures.
Ring structures can also have their own conformations.
The most common rings found in nature are five- and six-membered rings (most stable cyclics).

14. Cyclic Alkanes and Ring Strain continued…
Chemists attribute much of the instability of other ring sizes to ring strain, the increase in energy due to geometric constraints on the ring.
Ring strain can be quantified using heats of combustion, the energy given off in the form of heat (DH°) during a combustion reaction.
Any difference in the heat of combustion per CH2 group for two cyclic alkanes reflects a difference in ring strain per CH2 group.
The total ring strain is obtained by multiplying the strain per CH2 group by the number of CH2 groups, n.

15. Cyclic Alkanes and Ring Strain continued…

16. 4.5 The Most Stable Conformations of Cyclohexane, Cyclopentane, Cyclobutane, and Cyclopropane
Cyclohexane has no ring strain.
Cyclohexane is not a planar molecule.
Its lowest energy conformation resembles a chair and is therefore called a chair conformation.

17. 4.5 The Most Stable Conformations of Cyclohexane, Cyclopentane, Cyclobutane, and Cyclopropane continued…
In the chair conformation, all bond angles of the ring are about 111°, which is close to the ideal tetrahedral angle of 109.5°.
Cyclohexane also has little to no torsional strain, because all of the rotational conformations about the C-C bonds are staggered.

18. Cyclopentane
Cyclopentane is relatively stable in the envelope conformation.
Four of its five carbon atoms lie in one plane, with the fifth carbon outside of that plane.
Bond angles range from 102° to 106° in the envelope conformation. Therefore it has some angle strain.
Strain is minimized by adopting a nonplanar configuration.

19. Cyclopentane continued…

20. Cyclobutane
Most stable conformation is slightly puckered, with interior angles of about 88°.
Puckering of the cyclobutane ring relieves some torsional strain.

21. Cyclopropane
There is no alternative to having all three carbon atoms in the same plane, because three points define a plane.
All three angles of the ring are exactly 60° and all three C-C bonds are the same length, so the ring forms an equilateral triangle.

22. 4.6 Conformational Isomers: Cyclopentane, Cyclohexane, Pseudorotation, and Chair Flips
All five possible envelope conformations of cyclopentane interconvert via pseudorotation.
Pseudorotation occurs by partial rotations about the C-C bonds.

23. Cyclohexane’s Equivalent Carbon Atoms
All six carbon atoms in the chair conformation of cyclohexane are equivalent, making it impossible to distinguish among them.
Six hydrogen atoms occupy equatorial positions and six occupy axial positions.
Each carbon atom in cyclohexane is bonded to one of each.

24. Cyclohexane’s Equatorial and Axial Positions
Six hydrogen atoms occupy equatorial positions and six occupy axial positions.
Each carbon atom in cyclohexane is bonded to one of each.

25. Chair Flipping
A chair flip converts axial hydrogens into equatorial hydrogens, and vice versa.
Even though a chair flip interconverts axial and equatorial positions on a cyclohexane ring, it does not allow substituents to switch sides of the ring’s plane.

26. Energy Diagram for a Chair Flip
Rather than occurring in a single step, a cyclohexane chair flip involves multiple independent steps.
Throughout such a chair flip, cyclohexane assumes conformations known as the “half-chair,” the “twist-boat,” and the “boat.”

27. Cyclohexane Conformations Higher in Energy
The half-chair, twist-boat, and boat conformations in a chair flip are higher in energy than the chair conformation.
This energy difference is due to added ring strain.
Flagpole interactions between hydrogen atoms on an opposing pair of carbon atoms exist in the boat conformation.
This is a form of steric strain that is absent in the chair conformation.

28. Cyclohexane Conformations Higher in Energy continued…

29. 4.7 Strategies for Success: Drawing Chair Conformations of Cyclohexane
Chemists have devised the shorthand notation for drawing chair conformations.

30. 4.7 Strategies for Success: Drawing Chair Conformations of Cyclohexane continued…
The following provides the steps in order to successfully draw a cyclohexane chair conformation with 6 axial bonds and 6 equatorial bonds.

31. 4.8 Conformational Isomers: Monosubstituted Cyclohexane
If one of the hydrogen atoms in cyclohexane is replaced by another substituent, such as CH3, the results is a monosubstituted cyclohexane.
The two chair conformations of a monosubstituted cyclohexane are not equivalent.
Two nonequivalent chair forms are conformational isomers of each other.

32. Monosubstitution and Sterics
1,3-Diaxial interactions are a form of steric strain.
No such steric strain exists when the CH3 group is in the equatorial position.
A monosubstituted cyclohexane is more stable when the substituent is found in an equatorial position.
Bulky groups favor the equatorial position on a cyclohexane ring.

33. Monosubstitution and Sterics continued…

34. 4.9 Disubstituted Cyclohexanes, Cis and Trans Isomers, and Haworth Projections
A chair flip does not switch a substituent from one side of the plane to the other.
The cis–trans relationship between any pair of substituents on a cyclohexane ring is independent of the particular chair conformation the species is in.
Substituents that are cis to each other on a cyclohexane ring remain cis after a chair flip; substituents that are trans remain trans.
Since the cis–trans relationship of any pair of substituents is unaffected by a chair flip, it is often more convenient to represent substituted cyclohexanes using Haworth projections.

35. Haworth Projections
The ring is depicted as being planar and substituents are drawn perpendicular to that plane.
Every substituent on a cyclohexane ring favors an equatorial position rather than an axial position.
The most stable chair conformation can usually be predicted for a number of disubstituted cyclohexanes.

36. 4.10 Strategies for Success: Molecular Modeling Kits and Chair Flips
Because chair flips affect the three-dimensional arrangement of atoms in space and involve only rotations about single bonds, molecular modeling kits can be extremely helpful when comparing chair conformations.

37. 4.11 Constitutional Isomerism: Identifying Constitutional Isomers
Constitutional isomers, also called structural isomers, share the same molecular formula but differ in their connectivity.

38. 4.12 Constitutional Isomers: Index of Hydrogen Deficiency (Degree of Unsaturation)
Molecules that contain double bonds, triple bonds, or rings are said to be unsaturated because they have fewer than the maximum number of hydrogen atoms possible.

39. Index of Hydrogen Deficiency (IHD)
A molecule’s index of hydrogen deficiency (IHD), or degree of unsaturation, is defined as half the number of hydrogen atoms missing from that molecule compared to an analogous, completely saturated molecule.

40. 4.13 Strategies for Success: Drawing All Constitutional Isomers of a Given Formula
Being able to draw all constitutional isomers of a given molecular formula can be useful.
A systematic method to tackle these kinds of problems is helpful.
Steps to Obtain Different Isomers
1. Determine the formula’s IHD.
This will tell you the possible combinations of double bonds, triple bonds, and rings required in each isomer you draw.

41. Steps to Obtain Different Isomers continued...
2. Draw all possible structures that are unique in their connectivity.
Leave out any double bonds or triple bonds (they are added later).
Include rings. The number of rings must not exceed the IHD computed from Step 1; each structure, however, may contain fewer rings than the IHD.

42. Steps to Obtain Different Isomers continued...
For each structure generated in Step 2, add a double bond and/or a triple bond to achieve the total IHD calculated in Step 1.
For each structure generated in Step 3, add halogen atoms at various locations to generate as many unique connectivities as possible.

43. Steps to Obtain Different Isomers of C4H8F2
1. Determine the IHD
C4H8F2 has an IHD = 0.

44. C4H8F2 continued...
2. Draw isomers C4H8F2 that have no double bonds, triple bonds, or halogens.

45. C4H8F2 continued...
3. No double or triple bonds can be added because IHD=0. 4. Add the two F atoms. Begin by adding one F atom to various locations of the molecules.

46. C4H8F2 continued...
4. (cont’d) Add the second F atom to various locations.

47. C4H8F2 Isomers
4. (cont’d) Add the second F atom to various locations.

48. 4.15 Constitutional Isomers and Biomolecules: Amino Acids and Monosaccharides
Leucine and isoleucine, two naturally occurring amino acids, are constitutional isomers because they have the same molecular formula, but differ in their connectivity.
Monosaccharides provide many more examples of constitutional isomers.

49. Monosaccharide Isomers
Ribose and ribulose are isomers that differ by the location of the carbonyl group (C=O).
In ribose the carbonyl group belongs to an aldehyde.
In ribulose the carbonyl is part of a ketone.
Ribose is classified as an aldose, whereas ribulose is a ketose.
Glucose is similarly classified as an aldose, whereas fructose is a ketose.

50. 4.16 Saturation and Unsaturation in Fats and Oils
Oleic acid is a monounsaturated fatty acid, because it has just one C=C double bond, whereas linolenic acid is a polyunsaturated fatty acid, because it has three.

51. 4.16 Saturation and Unsaturation in Fats and Oils
Linoleic and linolenic acids are further classified as essential fatty acids because these are the only naturally occurring fatty acids that cannot be synthesized in the human body by any known chemical pathways.

52. Various Fatty Acids

53. Various Fatty Acids continued…

54. Various Fatty Acids continued…
The number of double bonds affects the melting points of these compounds because all C=C double bonds found in naturally occurring fatty acids are cis.
As a result, each double bond introduces a “kink” in the carbon chain (i.e., oleic acid has a kink in its chain).

55. Summary and Conclusions
Isomerism is a relationship between two or more molecular species.
Molecules are isomers of each other if they have the same molecular formula, but are different in some way.
Newman projections are used to show conformations about single bonds.
Torsional strain is the energy increase that appears in an eclipsed conformation.
Steric strain arises when groups not directly bonded together are in close proximity.

56. Summary and Conclusions continued…
Heats of combustion provide insight into ring strain for rings of various sizes.
Cyclohexane has no ring strain because it adopts a chair conformation, in which all angles are about 111°, and torsional and steric strain are minimized.
The two chair conformations of a monosubstituted cyclohexane are not equivalent.

57. Summary and Conclusions continued…
The bulkier a substituent, the greater its tendency to occupy an equatorial position.
Disubstituted cyclohexanes introduce cis and trans relationships relative to the plane of the ring.
The index of hydrogen deficiency is half the number of hydrogen atoms missing from that molecule compared to an analogous completely saturated molecule.