1. Surviving Chair Structures

2. Surviving Chair Structures A “How-to” Review

3. Step 1: Cyclohexane in 2-D 2 groups on the ring can be Cis (on the same side) or Trans (on opposite sides)

4. Step 1: Cyclohexane in 2-D 2 groups on the ring can be Cis or Trans: – Cis = Same Sides

5. Step 1: Cyclohexane in 2-D 2 groups on the ring can be Cis or Trans: – Trans = Opposite Sides

6. Step 1: Cyclohexane in 2-D Which is it? Cis or Trans?

7. Step 1: Cyclohexane in 2-D Answer: One Up… One Down… Trans…

8. Step 1: Cyclohexane in 2-D Which are they? Cis or Trans?

9. Step 1: Cyclohexane in 2-D How did you do?

10. Step 2: Draw cis-1, 3-dimethylcyclohexane

11. Start with a hexagon…

12. Step 2: Draw cis-1, 3-dimethylcyclohexane … then pick a position to be #1 (and ANY position can be #1)…

13. Step 2: Draw cis-1, 3-dimethylcyclohexane … then number around the ring (CW or CCW) to find #3(since you are drawing a 1,3-disubstituted ring)

14. Step 2: Draw cis-1, 3-dimethylcyclohexane … then attach the necessary groups (two methyl groups, in this case) to the #1 and #3 positions you’ve decided to use…

15. Step 2: Draw cis-1, 3-dimethylcyclohexane …then add stereochemistry to show the relative positions (cis = same side, trans = opposite sides). Since the compound is cis-1,3-dimethylcyclohexane, either of the answers below will be correct answers…

16. Step 2: Draw cis-1, 3-dimethylcyclohexane … as would these, depending on where you placed your #1 and #3 positions…

17. Step 3: Converting to a Chair structure

18. Chair structures are the 3-D representation of the cyclohexane ring… Remember that this view is from the side of the ring, not from above or below…

19. Step 3: Converting to a Chair structure First – let’s remind ourselves about the different positions on a chair structure…

20. Step 3: Converting to a Chair structure Every cyclohexane chair has six carbons, three that zig- zag up and three that zig-zag down… make sure you can identify them…

21. Step 3: Converting to a Chair structure On the positions that zig-zag UP, you will find the vertical UP AXIAL positions… on the positions that zig-zag DOWN, you will find the vertical DOWN AXIAL positions…

22. Step 3: Converting to a Chair structure On the positions that zig-zag UP, you will find the (semi- horizontal) DOWN EQUATORIAL positions… on the positions that zig-zag DOWN, you will find the (semi- horizontal) UP EQUATORIAL positions…

23. Step 3: Converting to a Chair structure All of the positions are shown below in one structure:

24. Step 3: Converting to a Chair structure All positions, together on the ring… make sure you can find them to draw them… Fill them in on the template shown… (answer on previous slide!)

25. Step 3: Converting to a Chair structure Translation required: wedges (or bold lines) in 2-D are the “UP” positions and dashes in 2-D are the “DOWN” positions… Up is Up and Down is Down, regardless of axial or equatorial…

26. Step 3: Converting to a Chair structure Recall that any position on the cyclohexane can be #1…

27. Step 3: Convert to a Chair structure …and any position on the chair form can be #1…

28. Step 3: Convert to a Chair structure …for practice and repetition’s sake (so you are less likely to make errors), choose your #1 on both and always stay in the same positions…

29. Step 3: Convert to a Chair structure …for the purpose of this example, we will use the #1 position on the hexagon shown below…

30. Step 3: Convert to a Chair structure …and this will correlate to the #1 position chosen here on this chair form… Remember that YOU can chose whichever #1 YOU want to use…

31. Step 3: Converting to a Chair structure If this is #1 on the hexagon, number the ring accordingly… CW or CCW…

32. Step 3: Converting to a Chair structure …then do likewise on the chair structure… again, CW versus CCW does not matter (its all RELATIVE to each other…)

33. Step 3: Converting to a Chair structure …now you can see what carbons on the hexagon form of cyclohexane correlate to the chair form of cyclohexane…

34. Step 3: Converting to a Chair structure Now let’s consider stereochemistry on the 2- dimensional version of cyclohexane…

35. Step 3: Converting to a Chair structure Try This: Draw trans-1,4-dichlorocyclohexane in 2- dimensions… I numbered this one CW, just for fun…

36. Step 3: Converting to a Chair structure How did you do? Your answer may not look exactly the same as the one below, but remember – its all RELATIVE… trans = one UP and one DOWN…

37. Step 3: Converting to a Chair structure Now you have to convert this into a chair structure… Watch your UP’s and DOWN’s…

38. Step 3: Converting to a Chair structure Position #1 has in this 2-D drawing an UP chloro group and position #4 has a DOWN chloro group…

39. Step 3: Converting to a Chair structure Label position 1 and 4 on the chair structure you are using and then transfer the information. Position 1 has an UP chloro group and position 4 has a DOWN chloro group…

40. Step 3: Converting to a Chair structure You need to fill in the groups on their positions (recall Axial and Equatorial positions). Position #1 has an UP chloro group and “up” on Position #1 will be AXIAL UP. Position #4 has a DOWN chloro group and “down” on Position #4 will be AXIAL DOWN.

41. Step 3: Converting to a Chair structure Try it again: Draw cis-1-bromo-3-methylcyclohexane as a chair structure… Start in 2-D… Go ahead – before you move to the next slide… Note that this time I numbered CW…

42. Step 3: Converting to a Chair structure Cis-1-bromo-3-methylcyclohexane, in 2-dimensions…

43. Step 3: Converting to a Chair structure Draw cis-1-bromo-3-methylcyclohexane as a chair structure. Convert to 3-dimensions – find the positions you need… then determine axial versus equatorial… Down on #1… Down on #3…

44. Step 3: Converting to a Chair structure Based on MY numbering, you should have had “cis” drawn as two substituents in the DOWN positions, as shown below. The chair structure would look like:

45. Step 3: Converting to a Chair structure But if you picked a different #1 on the chair, it might look like:

46. Step 3: Converting to a Chair structure And again: Draw trans-1-chloro-2-ethylcyclohexane as a chair structure. Start in 2-D…. Pick a #1 and number CW or CCW… Add your groups… Give them stereochemistry (wedges/dashes) to show “trans”…

47. Step 3: Converting to a Chair structure Trans-1-chloro-2-ethylcyclohexane in 2-D….

48. Step 3: Converting to a Chair structure Keep Going: Draw trans-1-chloro-2-ethylcyclohexane as a chair structure. Remember, there are lots of alternatives, depending on where you placed YOUR #1 and if you went CW or CCW to find #2…

49. Step 3: Converting to a Chair structure How did you do? Remember that when drawing trans- 1-chloro-2-ethylcyclohexane as a chair structure, there are lots of alternatives, depending on where you placed YOUR #1 and if you went CW or CCW to find #2…

50. Step 4: Drawing a Chair Flip Structure

51. When the chair structure of a cyclohexane ring does a “flip”, all of the axial substituents become equatorial and vice versa. Lock onto an “up” carbon (see #1 labeled below) and find its corresponding “down” carbon in the second conformation.

52. Step 4: Drawing a Chair Flip Structure Notice how Axial substituents swapped places with Equatorial substituents, but those that were “up” stayed “up” and “down” stayed “down”…

53. Step 4: Drawing a Chair Flip Structure Now try to transfer the information from one chair to its “flipped” conformation… Start with cis-1,3- dimethylcyclohexane… In this form, you see the two methyl groups are both UP… axial on #1, axial on #3…

54. Step 4: Drawing a Chair Flip Structure Draw the “flipped” conformation of cis-1,3-dimethyl- cyclohexane… Remember the #1 carbon in the first form is an “up” carbon and must therefore be a “down” carbon in the flipped chair form… Number accordingly…

55. Step 4: Drawing a Chair Flip Structure Then add the groups to the positions they belong on… #1 and #3, in this case… Remember the methyl groups are both “up” and must stay “up”… the axial methyls become equatorial… What will that look like?

56. Step 4: Drawing a Chair Flip Structure The diaxial UP positions become diequatorial UP positions:

57. Step 4: Drawing a Chair Flip Structure Now: Do it Again… Draw the following chair in its flipped form:

58. Step 4: Drawing a Chair Flip Structure Like before – lock onto the #1 position and flip the chair…

59. Step 4: Drawing a Chair Flip Structure There is a “down” chloro on MY #2 and an “up” alcohol group on MY #6… they must stay DOWN and UP, respectively… Axial becomes Equatorial and vice versa…

60. Step 4: Drawing a Chair Flip Structure One more time… Practice makes Perfect… Draw the chair flipped conformation for the compound shown below:

61. Step 4: Drawing a Chair Flip Structure Find the positions, as always… note the “up” groups (#2, #3 and #4)… none of the groups are “down”…two are equatorial, one is axial.. Now flip the axials and equatorials…

62. Step 4: Drawing a Chair Flip Structure And your answer should look like…

63. Step 5: Evaluating Chair Conformations and their Relative Energies If the two chair conformations are exactly the same, they will be the same energy. See the two examples below. Both sets are equal in energy…

64. Step 5: Evaluating Chair Conformations and their Relative Energies Make sure you can see that in this example you have two of the same groups, both up, with one axial while the other one is equatorial. They will have the same energy value.

65. Step 5: Evaluating Chair Conformations and their Relative Energies If the two chairs are not the same, they will have different energies, caused by different interactions (e.g. sterics). Note how in the first chair form, the bromo group is axial. In the second it is equatorial. They are different, and therefore different in energy values.

66. Step 5: Evaluating Chair Conformations and their Relative Energies So – why are they different in energy? The equatorial groups are a lower energy state because they point out and away from the molecule. The axial groups, however, have a higher energy steric interaction…

67. Step 5: Evaluating Chair Conformations and their Relative Energies The steric interaction that needs to be considered is called the A 1,3 interaction. It occurs for any axial group (top or bottom of ring) with the other axial groups on the same side (even H’s).

68. Step 5: Evaluating Chair Conformations and their Relative Energies The larger the group, the larger the energy value for the A 1,3 interaction.

69. Step 5: Evaluating Chair Conformations and their Relative Energies Molecules have been studied for their energy values. The A 1,3 interactions are quantified on tables that you can look up. As long as you know what X is, you can determine the energy of the system. For example, if X is a CH 3, the A 1,3 interaction is 0.9 kcal/mol for EACH CH 3 -H interaction…

70. Step 5: Evaluating Chair Conformations and their Relative Energies If the X group is a CH 3, the A 1,3 interactions occur with EACH H on the same side of the ring – thus the TOTAL energy is 0.9 kcal x 2… The total energy, for X = CH 3 would be 1.8 kcal/mol.

71. Step 5: Evaluating Chair Conformations and their Relative Energies If the X group is a CH 2 CH 3, the A 1,3 interactions occur with EACH H on the same side of the ring – thus the TOTAL energy is 0.95 kcal x 2… The total energy, for X = CH 2 CH 3 would be 1.9 kcal/mol.

72. Step 5: Evaluating Chair Conformations and their Relative Energies As the groups get larger, so does the energy of the conformation. If X group is a t-butyl group (-C(CH 3 ) 3 ], the A 1,3 interactions with the H’s are EACH 4.8 kcal/mol. The total energy, for X = C(CH 3 ) 3 would be 9.6 kcal/mol.

73. Step 5: Evaluating Chair Conformations and their Relative Energies If X is an isopropyl group, the A 1,3 interaction with one H would be 2.2 kcal/mol. What would be the total energy of the system shown below?

74. Step 5: Evaluating Chair Conformations and their Relative Energies With two isopropyl-H interactions, the total strain energy would be twice the value of one, or 4.4 kcal/mol.

75. Step 5: Evaluating Chair Conformations and their Relative Energies What about this one? Watch both the top AND the bottom of this ring. Remember the A 1,3 value for methyl-H is 0.9 kcal and for ethyl-H is 0.95 kcal/mol.

76. Step 5: Evaluating Chair Conformations and their Relative Energies With two methyl-H interactions on top and two ethyl-H interactions on the bottom, the total would be (2 x 0.9) + (2 x 0.95) = 3.7 kcal/mol total energy.

77. Step 5: Evaluating Chair Conformations and their Relative Energies Now compare the two chair conformations and determine which one is more stable?

78. Step 5: Evaluating Chair Conformations and their Relative Energies The ring with the most and largest groups in axial positions will be the most UNSTABLE and HIGHEST energy conformation. Which one is that, here?

79. Step 5: Evaluating Chair Conformations and their Relative Energies Yes, the first conformation is definitely more unstable. The isopropyl group has two A 1,3 interactions with H’s adding to 4.4 kcal/mol. The other has two methyl-H A 1,3 interactions that add to 1.8 kcal/mol. The first is higher energy! By 2.6 kcal/mol…

80. Surviving Chair Structures… In Conclusion… Cyclohexane and what you should be able to do: Draw in 2-D, showing stereochem Transfer to a chair conformation Draw the chair flipped conformation Identify the high or low energy conformation (or calculate the values, if I give you the table of values)

81. Surviving Chair Structures… In Conclusion… If you read through this IMMENSELY LONG slide show and found that it was helpful in learning about chair structures, drop me a note at jdiscord@towson.edu and let me know…jdiscord@towson.edu Thanks, Dr. Discordia