What are the forces in a molecular structure?

1. Torsional strain: Strain between groups on adjacent atoms. A-B-C-D. Worst when eclipsed; best when staggered. Bond angle strain: when a bond angle, A-B-C, diverges from the ideal (180, 120, 109) What are the forces in a molecular structure?

2. 120 deg. View from here yields view below. View from here yields view below. Rotation about C2 – C3 in butane Gauche conformation, Methyls closer, 60 deg, more repulsion, higher energy Anti conformation Methyls 180 deg, lower energy Anti!! Gauche!!

3. Energy Profile for Rotation in Butane Three hills (eclipsed) 120 apart. Three valleys (staggered forms) 120 apart;

4. Problem: Rotational profile of 2-methylbutane about C2-C3. First, staggered structures. 300 60 180 Rotate the front Me group. Relative energies….

5. Now, eclipsed…. 180 240 120 360 = 0 0 This was the high energy staggered structure,180 deg. Shown for reference only. Now relative energies…..

6. Now put on diagram… eclipsed staggered 120 60 360 300 180 240 0

7. Conformations of cycloalkanes: cyclopropane Planar ring (three points define a plane); sp3 hybrization: 109o. Hydrogens eclipsing. Torsional angle strain. Bond angle strain. Should be 109 but angle is 60o. Cyclopropane exhibits unusual reactivity for an alkane.

8. Folded, bent: less torsional strain but increased bond angle strain Conformation of cyclobutane Fold on diagonal Planar: eclipsing, torsional strain and bond angles of 90o

9. Cyclobutane molecular dynamics

10. Cyclopentane

11. Boat conformation Chair conformation Cyclohexane Ideal solution: Everything staggered and all angles tetrahedral.

12. Axial: Equatorial: Chair Conformation

13. Axial and Equatorial Axial Up/Equatorial Down: (A/E) Equatorial Up/Axial Down: (E/A) A/E E/A E/A A/E A/E E/A

14. Ring Flips Chair Boat or Twisted Boat A becomes E E becomes A Up stays Up Down stays Down Chair

15. Substituents: Axial vs Equatorial

16. Each repulsion is still about 3.6 kJ. Note that the gauche interaction in butane is about 3.8. Substituent Interactions Destabilizes axial substituent. Each repulsion is about 7.28/2 kJ = 3.6 kJ 1,3 diaxial repulsions Alternative description: gauche interactions

17. Newman Projection of methylcyclohexane Axial methyl group Equatorial methyl group gauche anti

18. 7.3 kJ (axial) 7.3 kJ (axial) Disubstituted cyclohexanes 1,2 dimethylcyclohexane 3.6 kJ (gauche) 3.6 kJ (gauche) interactions 0.0 kJ equatorial 0.0 kJ equatorial 7.3 + 3.6 = 10.9 kJ 7.3 + 3.6 = 10.9 kJ

19. 7.3 kJ (axial) 0.0 kJ equatorial 3.6 kJ (gauche) 0.0 kJ equatorial 7.3 kJ (axial) 0.0 kJ + 3.6 kJ = 3.6 kJ 14.6 kJ + 0.0 kJ = 14.6 kJ diequatorial diaxial

20. When does the gauche interaction occur?

21. Translate ring planar structure into 3D E/A A/E A/E Assume the tert-butyl group is equatorial. E/A A/E E/A Energy accounting No axial substituents One 1,2 gauche interaction between methyl groups, 3.6 kJ/mol Total: 3.6 kJ

22. Problem: Which has a higher heat of combustion per mole, A or B? 7.3 3.6 3.6 3.6 7.3 18.2 7.2 More repulsion, higher heat of combustion by 11.0 kJ/mol

23. Trans and Cis Decalin Now build cis decalin, both same side. Build trans decalin starting from cyclohexane, one linkage up, one down Trans sites used on the left ring Cis sites used on left ring. Trans sites used on the right ring Cis sites used on right ring. Trans decalin Locked, no ring flipping Cis decalin, can ring flip

24. Trans fusions determine geometry What is the geometry of the OH and CH3? E/A A/E A/E E/A E/A A/E Trans fusions, rings must use equatorial position for fusion. Rings are locked. The H’s must both be axial Work out axial / equatorial for the OH and CH3. OH is equatorial and CH3 is axial

25. Stereoisomerism and Chirality

26. Isomerism Constitutional Isomers: Same atoms but linked (bonded) together differently. Spatial orientation not important. No, different molecular formulae!! Are these constitutional isomers of hexane? Are these constitutional isomers of cis but-2-ene? Not this one! It is 2-butene. Cis / trans does not matter.

27. Stereoisomerism Stereoisomers: Same molecular formulae, same connectivity; same constitutional isomer. Different spatial orientation of the bonds. Are these stereoisomers of cis but-2-ene? How does the connectivity differ between these two?

28. Enantiomers and Diastereomers Two kinds of Stereoisomers Enantiomers: stereoisomers which are mirror objects of each other. Enantiomers are different objects, not superimposable. Diastereomers: stereoisomers which are not mirror objects of each other. If a molecule has one or more tetrahedral carbons having four different substituents then enantiomers will occur. If there are two or more such carbons then diastereomers may also occur.

29. Summary of Isomerism Concepts Isomers, contain same atoms, same formula Constitutional isomers, different connectivities, bonding. Stereoisomers, same connectivity, different three dimensional orientation of bonds Enantiomers, mirror objects Diastereomers, not mirror objects

30. Mirror Objects – Carbon with 4 different substituents. We expect enantiomers (mirror objects). Reflect! The mirror plane still relates the two structures. Notice that we can characterize or name the molecules by putting the blue in the back, drawing a circle from purple, to red, to green. Clockwise on the right and counterclockwise on the left. Arbitrarily call them R and S. Notice how the reflection is done, straight through the mirror! Arrange both structures with the light blue atoms towards the rear…. These are mirror objects. Are they the same thing just viewed differently ?? Can we superimpose them? We can superimpose two atoms. but not all four atoms. R S

31. Recap: Tetrahedral Carbon with four Different Substituents. Enantiomers Mirror objects. Different, not superimposable. Enantiomers Simple Rotation, Same Simple Rotation, Same

32. But the reflection might have been done differently. Position the mirror differently…. Reflection can give any of the following… Again. all three objects on the right are the mirror object of the structure above. They are different views of theenantiomer. A swap of two substituents is seen to be equivalent to a reflection at the carbon atom. Can you locate the mirror which would transform the original molecule into each mirror object? What is common to each of these reflection operations? In the course of each reflection, two substitutents are swapped. The other two remain unchanged. All three of these structures are the same, just made by different mirrors. The structures are superimposable. What rotations of the whole molecules are needed to superimpose the structures?

33. Now Superimposable mirror objects: Tetrahedral Carbon with at least two identical substituents. Reflection can interchange the two red substituents. Clearly interchanging the two reds leads to the same structure, superimposable! Remember it does not make any difference where the mirror is held for the reflection. This molecule does not have an enantiomer; the mirror object is superimposable on the original, the same object.

34. Summary A reflection on a tetrahedral carbon with four different substituents produces a different, non-superimposable structure, the enantiomer. A different three dimensional arrangement of the bonds is produced, a differentconfiguration. Such a carbon is called chiral. The carbon is a chiral center, a stereogenic center. If a tetrahedral carbon has two or more substituents which are the same then reflection produces the same structure, the same configuration. Such a carbon is called achiral. The swapping two of the substituents on the chiral carbon is equivalent to a reflection. There is only one mirror object produced by reflection, no matter where the mirror is located. It is either the same as the original structure (superimposable) or it is different (non-superimposable), the enantiomer.

35. Multiple reflections One reflection (swap of substituents) on a chiral carbon produce the enantiomer. Two reflections (swaps) yields the original back again. Even number (0, 2, 4…) of reflections (swaps) on a chiral carbon yields the original structure. An odd number (1, 3, 5…) yields the enantiomer. Enantiomers Enantiomers One swap Second swap Same molecule.

36. Repeating…. Three different substitutents. Reflection (in this plane) yields. Same, not enantiomers. Four different substituents. Reflection (in this plane) yields. Different, not superimposble, enantiomers.

37. Is a chiral carbon needed? No! Recall allene: Reflection (in this plane) yields. Different, not superimposable, enantiomers. The (distorted) tetrahedral array of the substitutents (huh??) suffices to allow for enantiomers.

38. Naming of configurations. S R A priority is assigned to each substituent on the chiral carbon Rotate the structure so that the lowest priority towards the rear. Draw an arc from the highest, to the next lower, to the next lower. If arc is clockwise it is R configuration. If arc is counterclockwise it is S.

39. Assigning Priorities 2 Start with first atom attached to chiral carbon C vs. F

40. When the first atom is the same…Examine what is bonded to it. Start with first atom attached to chiral carbon. No decision!! Examine atoms bonded to first atom O vs O N vs C

41. Example: assigning Priorities S configuration Substituents Highest,1 Lowest, 4 3 2 Assign on the basis of the atomic number of the first atom in the substituent. If the atoms being compared are the same examine the sets bonded to the atoms being compared. C has priority over H!!

42. More… If the first atom is the same and the second shell is the same then proceed to the atoms attached to the highest priority of the second shell. Examine the first atom, directly attached to the chiral atom. Examine the atoms bonded to the first atom (the second shell) . N vs N C vs C H vs H Examine atoms bonded to highest priority of second shell, N Cl vs F Cl wins!

43. Unsaturation So far have not worried about double or triple bonds. Double and triple bonds are expanded as shown below. Expanded into becomes

44. Let’s investigate what happens if low priority is positioned closer to us than chiral carbon… H towards the rear where it belongs… Now let’s swap any two substituents. We know that this produces the enantiomer, R. Swap the H and the Cl. Arc going in wrong direction because the low priority substituent is closer to us than the chiral center!!!!!! We are looking at the molecule from the wrong side. INVERT NAMING if LOW PRIORITY IS CLOSER THAN CHIRAL CENTER: Clockwise is S Counterclockwise is R

45. Physical Properties of Enantiomers Enantiomers: different compounds but have same Melting Point Boiling Point Density Enantiomers rotate plane polarized light in opposite directions. OPTICALLY ACTIVE!! The enantiomers rotate plane polarized light the same amount but in opposite directions. One clockwise; the other counterclockwise.

46. How to know if a compound is optically (in)active. Symmetry elements. The symmetry of an object is described in terms of symmetry elements. The use of a symmetry element may only interchange identical atoms. Proper Rotation. Rotation about an axis. Think of a propeller. Reflection plane (mirror plane). Inversion Point. An equidistant line through the center of the molecule. Improper Rotation. Rotation followed by reflection in plane perpendicular to axis. If a molecule has a reflection plane, inversion point, or improper rotation axis: inactive The presence of any of these symmetry elements except for proper rotation rules out enantiomers.

47. Rotational Axis

48. Reflection Plane

49. Inversion Point

50. Improper Rotational Axis