1. Dr. Wolf's CHM 201 & 202 3-1 Chapter 3 Conformations of Alkanes and Cycloalkanes

2. Dr. Wolf's CHM 201 & 202 3-2 Conformational Analysis of Ethane Conformations are different spatial arrangements of a molecule that are generated by rotation about single bonds.

3. Dr. Wolf's CHM 201 & 202 3-3 Eclipsed conformation Ethane

4. Dr. Wolf's CHM 201 & 202 3-4 Eclipsed conformation Ethane

5. Dr. Wolf's CHM 201 & 202 3-5 Staggered conformation Ethane

6. Dr. Wolf's CHM 201 & 202 3-6 Staggered conformation Ethane

7. Dr. Wolf's CHM 201 & 202 3-7 Projection formulas of the staggered conformation of ethane NewmanSawhorseHH HH HH HH H H H H

8. Dr. Wolf's CHM 201 & 202 3-8 Anti relationships HH HH HH HH H H H H Two bonds are anti when the angle between them is 180°. 180°

9. Dr. Wolf's CHM 201 & 202 3-9 Gauche relationships H H HH HH H H H H H H Two bonds are gauche when the angle between them is 60°. 60°

10. Dr. Wolf's CHM 201 & 202 3-10 An important point: The terms anti and gauche apply only to bonds (or groups) on adjacent carbons, and only to staggered conformations. An important point: The terms anti and gauche apply only to bonds (or groups) on adjacent carbons, and only to staggered conformations.

11. Dr. Wolf's CHM 201 & 202 3-11 0° 60° 120° 180° 240°300°360° 12 kJ/mol

12. Dr. Wolf's CHM 201 & 202 3-12 The eclipsed conformation of ethane is 12 kJ/mol less stable (higher energy) than the staggered.The eclipsed conformation of ethane is 12 kJ/mol less stable (higher energy) than the staggered. The eclipsed conformation is destabilized by torsional strain.The eclipsed conformation is destabilized by torsional strain. Torsional strain is the destabilization that results from eclipsed bonds.Torsional strain is the destabilization that results from eclipsed bonds. The eclipsed conformation of ethane is 12 kJ/mol less stable (higher energy) than the staggered.The eclipsed conformation of ethane is 12 kJ/mol less stable (higher energy) than the staggered. The eclipsed conformation is destabilized by torsional strain.The eclipsed conformation is destabilized by torsional strain. Torsional strain is the destabilization that results from eclipsed bonds.Torsional strain is the destabilization that results from eclipsed bonds. Torsional strain

13. Dr. Wolf's CHM 201 & 202 3-13 Conformational Analysis of Butane

14. Dr. Wolf's CHM 201 & 202 3-14 Conformational Analysis of Butane: C 2 -C 3 Rotation

15. Dr. Wolf's CHM 201 & 202 3-15 0° 60° 120° 180° 240°300°360° 3 kJ/mol 14 kJ/mol

16. Dr. Wolf's CHM 201 & 202 3-16 The gauche conformation of butane is 3 kJ/mol less stable than the anti.The gauche conformation of butane is 3 kJ/mol less stable than the anti. The gauche conformation is destabilized by van der Waals strain (also called steric strain)The gauche conformation is destabilized by van der Waals strain (also called steric strain) which results from atoms being too close together. The gauche conformation of butane is 3 kJ/mol less stable than the anti.The gauche conformation of butane is 3 kJ/mol less stable than the anti. The gauche conformation is destabilized by van der Waals strain (also called steric strain)The gauche conformation is destabilized by van der Waals strain (also called steric strain) which results from atoms being too close together. van der Waals strain gauche anti

17. Dr. Wolf's CHM 201 & 202 3-17 The conformation of butane in which the two methyl groups are eclipsed with each other is is the least stable of all the conformations.The conformation of butane in which the two methyl groups are eclipsed with each other is is the least stable of all the conformations. It is destabilized by both torsional strain (eclipsed bonds) and van der Waals strain.It is destabilized by both torsional strain (eclipsed bonds) and van der Waals strain. The conformation of butane in which the two methyl groups are eclipsed with each other is is the least stable of all the conformations.The conformation of butane in which the two methyl groups are eclipsed with each other is is the least stable of all the conformations. It is destabilized by both torsional strain (eclipsed bonds) and van der Waals strain.It is destabilized by both torsional strain (eclipsed bonds) and van der Waals strain. van der Waals strain eclipsed

18. Dr. Wolf's CHM 201 & 202 3-18 Conformational Analysis of Higher Alkanes

19. Dr. Wolf's CHM 201 & 202 3-19 The most stable conformation of unbranched alkanes has anti relationships between carbons Hexane

20. Dr. Wolf's CHM 201 & 202 3-20 The Shapes of Cycloalkanes: Planar or Nonplanar?

21. Dr. Wolf's CHM 201 & 202 3-21 Adolf von Baeyer (19th century) assumed cycloalkanes are planar polygonsassumed cycloalkanes are planar polygons distortion of bond angles from 109.5° gives angle strain to cycloalkanes with rings either smaller or larger than cyclopentanedistortion of bond angles from 109.5° gives angle strain to cycloalkanes with rings either smaller or larger than cyclopentane Baeyer deserves credit for advancing the idea of angle strain as a destabilizing factor.Baeyer deserves credit for advancing the idea of angle strain as a destabilizing factor. But Baeyer was incorrect in his belief that cycloalkanes were planar.But Baeyer was incorrect in his belief that cycloalkanes were planar.

22. Dr. Wolf's CHM 201 & 202 3-22 Types of Strain Torsional strainTorsional strain strain that results from eclipsed bonds van der Waals strain (steric strain)van der Waals strain (steric strain) strain that results from atoms being too close together angle strainangle strain strain that results from distortion of bond angles from normal values Torsional strainTorsional strain strain that results from eclipsed bonds van der Waals strain (steric strain)van der Waals strain (steric strain) strain that results from atoms being too close together angle strainangle strain strain that results from distortion of bond angles from normal values

23. Dr. Wolf's CHM 201 & 202 3-23 Measuring Strain in Cycloalkanes Measuring Strain in Cycloalkanes Heats of combustion can be used to compare stabilities of isomers.Heats of combustion can be used to compare stabilities of isomers. But cyclopropane, cyclobutane, etc. are not isomers.But cyclopropane, cyclobutane, etc. are not isomers. All heats of combustion increase as the number of carbon atoms increase.All heats of combustion increase as the number of carbon atoms increase.

24. Dr. Wolf's CHM 201 & 202 3-24 Measuring Strain in Cycloalkanes Measuring Strain in Cycloalkanes Therefore, divide heats of combustion by number of carbons and compare heats of combustion on a "per CH 2 group" basis.Therefore, divide heats of combustion by number of carbons and compare heats of combustion on a "per CH 2 group" basis.

25. Dr. Wolf's CHM 201 & 202 3-25 Heats of Combustion of Cycloalkanes CycloalkanekJ/molPer CH 2 Cyclopropane2,091697 Cyclobutane2,721681 Cyclopentane3,291658 Cyclohexane3,920653 Cycloheptane4,599657 Cyclooctane5,267658 Cyclononane5,933659 Cyclodecane6,587659

26. Dr. Wolf's CHM 201 & 202 3-26 Heats of Combustion of Cycloalkanes CycloalkanekJ/molPer CH 2 According to Baeyer, cyclopentane should have less angle strain than cyclohexane. Cyclopentane3,291658 Cyclohexane3,920653 The heat of combustion per CH 2 group is less for cyclohexane than for cyclopentane. Therefore, cyclohexane has less strain than cyclopentane.

27. Dr. Wolf's CHM 201 & 202 3-27 Adolf von Baeyer (19th century) assumed cycloalkanes are planar polygonsassumed cycloalkanes are planar polygons distortion of bond angles from 109.5° gives angle strain to cycloalkanes with rings either smaller or larger than cyclopentanedistortion of bond angles from 109.5° gives angle strain to cycloalkanes with rings either smaller or larger than cyclopentane Baeyer deserves credit for advancing the idea of angle strain as a destabilizing factor.Baeyer deserves credit for advancing the idea of angle strain as a destabilizing factor. But Baeyer was incorrect in his belief that cycloalkanes were planar.But Baeyer was incorrect in his belief that cycloalkanes were planar.

28. Dr. Wolf's CHM 201 & 202 3-28 Small Rings CyclopropaneCyclobutane

29. Dr. Wolf's CHM 201 & 202 3-29 CyclopropaneCyclopropane sources of strain: torsional strain angle strain

30. Dr. Wolf's CHM 201 & 202 3-30 CyclobutaneCyclobutane nonplanar conformation relieves some torsional strain angle strain present

31. Dr. Wolf's CHM 201 & 202 3-31 Cyclopentane

32. Dr. Wolf's CHM 201 & 202 3-32 CyclopentaneCyclopentane all bonds are eclipsed planar conformation destabilized by torsional strain

33. Dr. Wolf's CHM 201 & 202 3-33 Nonplanar conformations of cyclopentane EnvelopeHalf-chair Relieve some, but not all, of the torsional strain. Envelope and half-chair are of similar stability and interconvert rapidly.

34. Dr. Wolf's CHM 201 & 202 3-34 Conformations of Cyclohexane heat of combustion suggests that angle strain is unimportant in cyclohexane tetrahedral bond angles require nonplanar geometries

35. Dr. Wolf's CHM 201 & 202 3-35 Chair is the most stable conformation of cyclohexane All of the bonds are staggered and the bond angles at carbon are close to tetrahedral.

36. Dr. Wolf's CHM 201 & 202 3-36 Boat conformation is less stable than the chair All of the bond angles are close to tetrahedral but close contact between flagpole hydrogens causes van der Waals strain in boat. 180 pm

37. Dr. Wolf's CHM 201 & 202 3-37 Boat conformation is less stable than the chair Eclipsed bonds bonds gives torsional strain to boat.

38. Dr. Wolf's CHM 201 & 202 3-38 Skew boat is slightly more stable than boat Less van der Waals strain and less torsional strain in skew boat. Boat Skew boat

39. Dr. Wolf's CHM 201 & 202 3-39 The chair conformation of cyclohexane is the most stable conformation and derivatives of cyclohexane almost always exist in the chair conformation

40. Dr. Wolf's CHM 201 & 202 3-40 Axial and Equatorial Bonds in Cyclohexane

41. Dr. Wolf's CHM 201 & 202 3-41 The 12 bonds to the ring can be divided into two sets of 6.

42. Dr. Wolf's CHM 201 & 202 3-42 Axial bonds point "north and south" 6 bonds are axial

43. Dr. Wolf's CHM 201 & 202 3-43 Equatorial bonds lie along the equator 6 bonds are equatorial

44. Dr. Wolf's CHM 201 & 202 3-44 Conformational Inversion (Ring-Flipping) in Cyclohexane

45. Dr. Wolf's CHM 201 & 202 3-45 Conformational Inversion chair-chair interconversion (ring-flipping) rapid process (activation energy = 45 kJ/mol) all axial bonds become equatorial and vice versa

46. Dr. Wolf's CHM 201 & 202 3-46

47. Dr. Wolf's CHM 201 & 202 3-47 Half- chair

48. Dr. Wolf's CHM 201 & 202 3-48 Half- chair Skew boat

49. Dr. Wolf's CHM 201 & 202 3-49 Half- chair Skew boat

50. Dr. Wolf's CHM 201 & 202 3-50 Half- chair Skew boat

51. Dr. Wolf's CHM 201 & 202 3-51 45 kJ/mol 23 kJ/mol

52. Dr. Wolf's CHM 201 & 202 3-52 Conformational Analysis of Monosubstituted Cyclohexanes most stable conformation is chair substituent is more stable when equatorial

53. Dr. Wolf's CHM 201 & 202 3-53 MethylcyclohexaneMethylcyclohexane 5% 95% Chair chair interconversion occurs, but at any instant 95% of the molecules have their methyl group equatorial. Axial methyl group is more crowded than an equatorial one. CH 3

54. Dr. Wolf's CHM 201 & 202 3-54 MethylcyclohexaneMethylcyclohexane 5% 95% Source of crowding is close approach to axial hydrogens on same side of ring. Crowding is called a "1,3-diaxial repulsion" and is a type of van der Waals strain.

55. Dr. Wolf's CHM 201 & 202 3-55 FluorocyclohexaneFluorocyclohexane 40% 60% Crowding is less pronounced with a "small" substituent such as fluorine. Size of substituent is related to its branching. F F

56. Dr. Wolf's CHM 201 & 202 3-56 tert-Butylcyclohexane Less than 0.01% Greater than 99.99% Crowding is more pronounced with a "bulky" substituent such as tert-butyl. tert-Butyl is highly branched. C(CH 3 ) 3

57. Dr. Wolf's CHM 201 & 202 3-57 tert-Butylcyclohexane van der Waals strain due to 1,3-diaxial repulsions

58. Dr. Wolf's CHM 201 & 202 3-58 Disubstituted Cycloalkanes: Stereoisomers Stereoisomers are isomers that have same constitution but different arrangement of atoms in space

59. Dr. Wolf's CHM 201 & 202 3-59 IsomersIsomers Constitutional isomers StereoisomersStereoisomers

60. Dr. Wolf's CHM 201 & 202 3-60 1,2-Dimethylcyclopropane1,2-Dimethylcyclopropane There are two stereoisomers of 1,2-dimethylcyclopropane. They differ in spatial arrangement of atoms.

61. Dr. Wolf's CHM 201 & 202 3-61 1,2-Dimethylcyclopropane1,2-Dimethylcyclopropane cis-1,2-Dimethylcyclopropane has methyl groups on same side of ring. trans-1,2-Dimethylcyclopropane has methyl groups on opposite sides.

62. Dr. Wolf's CHM 201 & 202 3-62 Relative stabilities of stereoisomers may be determined from heats of combustion.

63. Dr. Wolf's CHM 201 & 202 3-63 3371 kJ/mol 3366 kJ/mol van der Waals strain makes cis stereoisomer less stable than trans

64. Dr. Wolf's CHM 201 & 202 3-64 Conformational Analysis of Disubstituted Cyclohexanes

65. Dr. Wolf's CHM 201 & 202 3-65 1,4-Dimethylcyclohexane stereoisomers cistrans CH 3 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. H3CH3CH3CH3C H H H3CH3CH3CH3C CH 3 H H

66. Dr. Wolf's CHM 201 & 202 3-66 Conformational analysis of cis-1,4-dimethylcyclohexane CH 3 Two equivalent conformations; each has one axial methyl group and one equatorial methyl group H3CH3CH3CH3C H H H CH 3 H H H3CH3CH3CH3C H

67. Dr. Wolf's CHM 201 & 202 3-67 Conformational analysis of trans-1,4-dimethylcyclohexane Two conformations are not equivalent; most stable conformation has both methyl groups equatorial. CH 3 H3CH3CH3CH3C H H H H3CH3CH3CH3CH H H3CH3CH3CH3C H

68. Dr. Wolf's CHM 201 & 202 3-68 1,2-Dimethylcyclohexane stereoisomers cistrans 5223 kJ/mol 5217 kJ/mol less stable more stable Analogous to 1,4 in that trans is more stable than cis. CH 3 H H H3CH3CH3CH3C H H

69. Dr. Wolf's CHM 201 & 202 3-69 Conformational analysis of cis-1,2-dimethylcyclohexane Two equivalent conformations; each has one axial methyl group and one equatorial methyl group CH 3 H H H H H H

70. Dr. Wolf's CHM 201 & 202 3-70 Conformational analysis of trans-1,2-dimethylcyclohexane Two conformations are not equivalent; most stable conformation has both methyl groups equatorial. CH 3 H3CH3CH3CH3C H H H H H H3CH3CH3CH3C H

71. Dr. Wolf's CHM 201 & 202 3-71 1,3-Dimethylcyclohexane stereoisomers cistrans 5212 kJ/mol 5219 kJ/mol more stable less stable Unlike 1,2 and 1,4; cis-1,3 is more stable than trans. H3CH3CH3CH3C CH 3 H H H3CH3CH3CH3C H H

72. Dr. Wolf's CHM 201 & 202 3-72 Conformational analysis of cis-1,3-dimethylcyclohexane Two conformations are not equivalent; most stable conformation has both methyl groups equatorial. H3CH3CH3CH3C H H CH 3 H3CH3CH3CH3C H H H H

73. Dr. Wolf's CHM 201 & 202 3-73 Conformational analysis of trans-1,3-dimethylcyclohexane Two equivalent conformations; each has one axial and one equatorial methyl group. H3CH3CH3CH3C H H CH 3 H H3CH3CH3CH3C H H3CH3CH3CH3C H H

74. Dr. Wolf's CHM 201 & 202 3-74 Table 3.2 Heats of Combustion of Isomeric Dimethylcyclohexanes CompoundOrientation-  H° cis-1,2-dimethylax-eq5223 trans-1,2-dimethyleq-eq5217* cis-1,3-dimethyleq-eq5212* trans-1,3-dimethylax-eq5219 cis-1,4-dimethylax-eq5219 trans-1,4-dimethyleq-eq5212* *more stable stereoisomer of pair

75. Dr. Wolf's CHM 201 & 202 3-75 Medium and Large Rings

76. Dr. Wolf's CHM 201 & 202 3-76 Cycloheptane and Larger Rings More complicated than cyclohexane. Common for several conformations to be of similar energy. Principles are the same, however. Minimize total strain.

77. Dr. Wolf's CHM 201 & 202 3-77 Polycyclic Ring Systems Contain more than one ring….. bicyclic, tricyclic, tetracyclic, etc. Contain more than one ring….. bicyclic, tricyclic, tetracyclic, etc.

78. Dr. Wolf's CHM 201 & 202 3-78 Number of rings equals minimum number of bond disconnections required to give a noncyclic species

79. Dr. Wolf's CHM 201 & 202 3-79 MonocyclicMonocyclic requires one bond disconnection requires one bond disconnection

80. Dr. Wolf's CHM 201 & 202 3-80 BicyclicBicyclic requires two bond disconnections

81. Dr. Wolf's CHM 201 & 202 3-81 BicyclicBicyclic requires two bond disconnections

82. Dr. Wolf's CHM 201 & 202 3-82 Types of ring systems spirocyclic fused ring bridged ring

83. Dr. Wolf's CHM 201 & 202 3-83 SpirocyclicSpirocyclic one atom common to two rings Spiro[4.5]decane

84. Dr. Wolf's CHM 201 & 202 3-84 Fused ring adjacent atoms common to two rings two rings share a common side Bicyclo[4.3.0]nonane

85. Dr. Wolf's CHM 201 & 202 3-85 Bridged ring nonadjacent atoms common to two rings Bicyclo[3.2.1]octane

86. Dr. Wolf's CHM 201 & 202 3-86 SteroidsSteroids carbon skeleton is tetracyclic

87. Dr. Wolf's CHM 201 & 202 3-87 Heterocyclic Compounds

88. Dr. Wolf's CHM 201 & 202 3-88 Heterocyclic Compound a cyclic compound that contains an atom other than carbon in the ring (such atoms are called heteroatoms) typical heteroatoms are N, O, and S

89. Dr. Wolf's CHM 201 & 202 3-89 Oxygen-containing heterocycles O Ethylene oxide O Tetrahydrofuran TetrahydropyranOO

90. Dr. Wolf's CHM 201 & 202 3-90 Nitrogen-containing heterocycles Pyrrolidine PiperidineNH N H

91. Dr. Wolf's CHM 201 & 202 3-91 Sulfur-containing heterocycles SSS S S SS CH 2 CH 2 CH 2 CH 2 COH O Lipoic acid Lenthionine

92. Dr. Wolf's CHM 201 & 202 3-92 End of Chapter 3