Conformational Analysis

Transcription

1 onformational Analysis

2 Free Rotation about arbon-arbon Single Bonds A carbon carbon single bond is formed by the end-on overlap of cylindrically symmetrical sp 3 orbitals. Therefore, attached carbon atoms can rotate about the bond without changing the amount of orbital overlap.

3 onformations of Alkanes A. Atoms may freely rotate about Single bonds B. Such rotation is not evident in very simple molecules, but can be demonstrated in models of larger molecules 1. Methane - 4 Rotation does not change the spacial relationship between hydrogen atoms. 2. Ethane - 33 Rotation does change the spatial relationship between hydrogen atoms

4 onformations of Alkanes ONFORMATIONS - Different arrangements of atoms in a molecule which can be interconverted by rotation about single bonds In a given sample of a compound, the molecules usually exist as a mixture of conformations. One or two conformations are usually the most stable. Though they may appear different on paper, different conformers represent the same molecule

5 onformational hanges Newman Projections

6 Newman Projections

7 onformations of Ethane eclipsed staggered

8 eclipsed 12 kj/mol Potential Energy staggered Dihedral angle 0º 60º 120º 180º 240º 300º 360º

9 onformations of Propane 3

10 onformations of Propane eclipsed staggered

11 3 eclipsed Potential Energy 14 kj/mol 3 staggered Dihedral angle 0º 60º 120º 180º 240º 300º 360º

12 onformations of Butane Butane has three carbon carbon single bonds, and the molecule can rotate about each of them. Rotation about a carbon carbon single bond is not completely free because of the energy difference between the staggered and eclipsed conformations.

13 º 60º 120º 180º 240º 300º 360º Dihedral angle

14 3 3 eclipsed gauche planar trans 16 kj/mol 3 4 kj/mol 3 19 kj/mol 0º 60º 120º 180º 240º 300º 360º Dihedral angle

15 ycloalkanes Structure and Stability

16 ycloalkanes Structure and Stability Bond angles far removed from the ideal 109.5º

17 Bond angles close to the ideal 109.5º cyclopentane cycloheptane cyclohexane Bond angles 109.5º

18 ombustion of ycloalkanes n2n + (cyclo-alkane) (3n) 2 O2 no2 + n2o + Δcomb (kj/mol) n Δcomb Δcomb/ Total Angle Strain Angle Strain/

19 yclohexane onformations

20 yclohexane onformations hair Boat

21 yclohexane onformations

22 yclohexane onformations Because the chair conformers are the most stable of the conformers, at any instant more molecules of cyclohexane are in chair conformations than in any other conformation.

23 yclohexane onformations Why is the Boat onformer Less Stable?

24 yclohexane onformations Why is the Boat onformer Less Stable? eclipsing interactions flagpole interactions

25 yclohexane onformations Axial and Equatorial Positions

26 yclohexane onformations Axial and Equatorial Positions a e a a e e e e a a e a

27 yclohexane onformations Axial and Equatorial Positions

28 onformations of Mono-substituted yclohexanes

29 yclohexane onformations Axial and Equatorial Positions A substituent is in the equatorial position in one conformation and axial in the other conformation. The conformation with the substituent in the equatorial position is more stable.

30 yclohexane onformations Why is a onformer with an Axial Substituent Less Stable? Steric interaction between an axial substituent and a substituent on a parallel bond is called 1,3-diaxial interaction. The hydrogens of the methyl group substituent are more crowded when the methyl group is in the axial position than when it is in the equatorial position.

31 yclohexane onformations Steric Strain Associated with 1,3-Diaxial Interactions Y (kj/mol) per interaction -F 0.5 -l,-br 1.0 -O (3) (3) Y

32 Axial-to-equatorial ring-flip equilibrium: Keq Keq = [equatorial]/[axial]

33 Axial-to-equatorial ring-flip equilibrium constants for several monosubstituted cyclohexanes at 25º. Keq Substituent Keq Substituent Keq 1 N- 1.4 methyl- 18 F- 1.5 ethyl 21 l- 2.4 isopropyl 35 Br-,I- 2.2 tert-butyl O- 5.4 The equilibrium constants get larger as the substituents get larger in size.

34 yclic Alkanes - cis/trans Isomerism onsider the formula 510 There appear to be five constitutional isomers which do not contain a double bond:

35 yclic Alkanes - cis/trans Isomerism 1,2-Dimethylcyclopropane can actually exist as two geometric isomers: cis-1,2-dimethylcyclopropane trans-1,2-dimethylcyclopropane stereoisomers

36 onformations of Di-substituted yclohexanes Basis of Equilibria: The avoidance of 1,3 diaxial interactions and the preference of large substituents for the equatorial position.

37 Predict the favored conformation for: ? 3 1,1-dimethylcyclohexane ? t-butyl-1-methylcyclohexane ,3-interaction between and 3: +3.8 kj/mol 1,3-interaction between and (3)3: kj/mol

38 Predict the favored conformation for: 3 3 3? cis-1,2-dimethylcyclohexane 3 3? trans-1,2-dimethylcyclohexane 3 1,3-interaction between and 3: +3.8 kj/mol gauche-interaction between 3 and 3 = +4 kj/mol

39 Predict the favored conformation for: 3? cis-1,3-dimethylcyclohexane? trans-1,3-dimethylcyclohexane 1,3-interaction between 3 and 3 = kj/mol 1,3-interaction between and 3 = +3.8 kj/mol

40 Steric Strain Associated with 1,3-Diaxial Interactions Y (kj/mol) per interaction -F 0.5 -l,-br 1.0 -O (3) (3) Y

41 2. The diaxial conformation of cis-1,3-dimethylcyclohexane is about 23 kj/mol less stable than the diequatorial conformation. Estimate the steric strain caused by the interaction of two axial methyl groups ? 3 no 1,3 interactions 2 x (1,3-3/ interactions) = 7.6 kj/mol 1 x (1,3-3/3 interaction) =? kj/mol Total difference in stability = 23 kj/mol ontribution of 3/3 interaction = 15.4 kj/mol

42 3. One of the two chair structures of cis-1-chloro-3-methylcyclohexane is more stable than the other by 15.5 kj/mol. Which one is it? What is the energy cost of a 1,3-diaxial interaction between a chlorine and a methyl group? l 3 3? l no 1,3 interactions 1 x (1,3-l/ interaction) = 1.0 kj/mol 1 x (1,3-3/ interaction) = 3.8 kj/mol 1 x (l/3 interaction) =? kj/mol Total difference in stability = 15.5 kj/mol ontribution of l/3 interaction = 10.7 kj/mol

43 Polycyclic Systems

44 Decalin System From a structural standpoint, it is important to consider the characteristics of a fused ring system.

45 Decalin System

46 Steroids Steroids are high molecular weight, nonhydrolyzable lipids that contain the steroid ring structure: D A B Steroids include cholesterol, adrenocortical and sex hormones, and bile salts. The biological effects vary considerably and depend on functional groups attached to the rings and shape.

47 holesterol is the major steroid in animals. It contains 8 tetrahedral stereocenters, but exists as a single stereoisomer. 1) ardiovascular disease 2) Membrane component 3) Precursor to other steroids. O

48 ortisol: 1) Adrenocortical hormone 2) Metabolic regulator 3) Immune regulator O O O O O

49 Testosterone: 1) Sex hormone 2) Reproductive cycle 3) Growth and development O O

50 holic acid: 1) Secreted by gall bladder 2) Active in digestion of fats 3) A/B ring cis fused O -O O O O