Chapter 3 Conformational, Steric , and, Stereo Electronic Effects

1. Chapter 3 Conformational, Steric , and, Stereo Electronic Effects Advanced Organic Chemistry (Chapter 3) Javanshir

2. 3.1 Steric Strain and Molecular Mechanics E(r): Stretching and compressing energy of single bonds E(q): Bond angle distortion energy E(f): Torsional strain E(d): Energy result from non-bonded interactions

3. Non-Bonded Interactions: The most difficult contribution to evaluate بر همکنش جاذبه ای میان دو اتم بدون بار(ناشی ازپلاریزاسیون و دو قطبی های موقت) با نزدیک شدن فاصله آنها به حاصل جمع شعاع واندروالسی، افزایش می یابد. ولی از آن پس نیروی دافعه است که افزایش می یابد. London forces vary inversely with the sixth power of internuclear distance and become negligible as internuclear separation increases. At distances smaller than the sum of the van der Waals radii, the much stronger electron-electron repulsive forces are dominant.

4. Shortly, we will learn that for some hydrocarbon molecules, van der Waals repulsions are a major factor in conformational preferences and energy barriers, but that is not the case for ethane. Careful analysis of the van der Waals radii show that the hydrogens do not come close enough to account for the barrier to rotation. Furthermore, the barrier of just under 3 kcal is applicable to more highly substituted single bonds. The barrier becomes significantly larger only when additional steric components are added, so the barrier must be an intrinsic property of the bond and not directly dependent on substituent size. The barrier to rotation is called the torsional barrier. • the main factor responsible for the torsional barrier is s-s∗ delocalization (hyperconjugation), which favors the staggered conformation. The rate of rotation is about 6×109 s−1 at 25oC.

5. Torsion angle for rotation about C2-C3 bond n-Butane:

6. Substitution of a methyl group for hydrogen on one of the carbon atoms produces an increase of 0.4–0.6 kcal/mol in the height of the rotational energy barrier.

7. جمعیت صورت بندی های گوناگون طبق معادله زیر به دست می آید. DG° = -RT ln Keq percentage

8. DS° = -R ln w , T = 298 K , R = 1.987 cal/mol.K w: Number of states DS° = -R ln 2 = -1.38 cal

9. DG° = DH° - TDS° DG° = -0.8 x 1000 – 298(-1.38) DG° = -388.8 cal= -0.39 kcal DG° = -RT ln Keq Keq = 1.9 at 298 K

10. 3.2 Conformations of Acyclic Molecules Rotational Energy Barrier: CH3-SiH3: 1.7 kcal/mol CH3-CH3: 2.88 kcal/mol C- C bond length: 1.54 Å C- Si bond length: 1.87 Å (CH3-CH2X): Rotational barrier energy is almost constant (3.2-3.7 kcal/mol) The heavier halogens: Longer Van der Waals radii Longer bond length

12. Changing the atom bound to a methyl group from carbon to nitrogen 3 2 1

13. Terminal Alkenes: The eclipsed conformation is preferred by about 2 kcal/mol. MOT:This stabilization arises from s-p∗ interactions. The major effect is a transfer of electron density from the methyl C−H bonds to the empty p∗ orbital.

14. The two hydrogen AOs of the methyl groups are not in the nodal plane of the p bond and can interact with 2pz of C-2 H I n t e r a c t i o n b e t w e e n h y d r o g e n 1 s o r b i t a l s a n d c a r b o n 2 p o r b i t a l s s t a b i l i z e t h e e c l i p s e d c o n f o r m a t i o n o f p r o p e n e . z More stable

15. relative energies: bisected eclipsed • Further substitution can introduce van der Waals repulsions that influence conformational equilibria. • example methyl-methyl gauche interaction the two eclipsed conformations are of approximately equal energy

16. Effect of increasing the size of the group at C-3: A B Increasing the size of the group at C(3) increases the preference for the eclipsed conformation analogous to B at the expense of A.

17. Carbonyl Compounds are eclipsed rather than bisected anti gauche

18. 1,3-butadien در 3،1-دی ان ها باید پیوند های دوگانه در یک صفحه قرار گیرند به طوری که همپوشانی اوربیتال ها و عدم استقرار الکترون ها امکان پذیر گردد. در صورت بندی کج یا اریبی (skew) دافعه بین هیدروژن ها کم می شود

19. a,b-Unsaturated compounds

20. Mesityl Oxide

21. 3-2-صورت بندی های مشتقات سیکلوهگزان زوایای پشچش از حالت ایده آل (o60) انحراف دارد و پشوند های C-H کاملا موازی نیستند.

22. برهمکنش میل پرچمی

23. سیکلو هگزان برهمکنش میل پرچمی

24. Effect of Substituent 1,3-diaxial Interaction

25. Appearance of NMR spectra for system undergoing site exchange at various rates.

26. Low Temperature Studies Cyclohexyl Chloride: Crystallization at -150 °C Only equatorial Conformer Dynamic NMR of Cyclohexyl Iodide at -80 °C Jae=3.5 Hz Jaa=12Hz

28. tert-Buthylcyclohexane Locked System: trans-Decaline Trans decalin is incapable of chair-chair inversion. The trans-decalin system is a “conformationally locked” • Equilibration of the cis and trans isomers favors the trans isomer by about 2.8 kcal/mol. Note that this represents a change in configuration, not conformation.

30. The energy difference can be analyzed by noting that the cis isomer has an inter-ring gauche-butane interaction that is not present in the trans isomer. • There are also cross-ring interactions between the axial hydrogens on the concave surface of the molecule.

32. Conformations in which there is a 1,3-diaxial interaction between substituent groups larger than hydrogen are destabilized by van der Waals repulsion. 1,1,3,5-tetramethylcyclohexane

33. Substituted Alkylidenecyclohexanes at C-2: Alkylidenecyclohexanes bearing alkyl groups of moderate size at C(2) tend to adopt the conformation with the alkyl group axial, in order to relieve unfavorable interactions with the alkylidene group. This results from van der Waals repulsion between the alkyl group in the equatorial position and cis substituents on the exocyclicdouble bond, and is an example of 1,3-allylic strain. The repulsive energy is small for methylenecyclohexanes Allylic Strain

34. Influence of 1,3-allylic strain on Z-alkene conformations. Preferred conformation for 4-substitued 2-alkenes is C. If R1 and R2 are different, the two faces become nonequivalent => stereoselective reactions at double bond. Ex:

35. more stable • An alkyl group at C(2) of a cyclohexanone ring is more stable in the equatorial than in the axial orientation. The equatorial orientation is eclipsed with the carbonyl group and corresponds to the more stable conformation of open-chain keto. Substituents at C-2 can assume an axial or equatorial position depending on steric and electronic influences.

36. Effect of Solvent Polarity of Preferred Conformer a-Haloketone effect:

37. DGo= - 1.3-1.4 kcal/mol

38. 3.4 Carbocyclic Rings Other Than Six-Membered angle between the planes =56o. شبه محوری در صورت بندی سیس هر دو استخلاف در موقعیت های شبه استوایی قرار میگیرند این سه کربن در یک صفحه قرار دارند As ring size increases, there are progressively more conformations that have to be considered.

39. Cycloheptane: Four conformations have been calculated to be particularly stable Cyclooctane: (11 conformers) Larger Rings (Diamond Lattice Structure):

40. For cyclodecane there are 18 conformers. Examination of the boat-chair-boat conformation reveals that the source of most of this strain is the close van der Waals contacts between two sets of three hydrogens on either side of the molecule, as indicated in the drawing below. Distortion of the molecule to twist forms relieves this interaction but introduces torsional strain.

41. 3.5 The Effect of Heteroatoms on conformational Equilibria C-C (1.54 Å) Thiane Piperidine Tetrahydropyran C-O(1.43 Å) C-N(1.47 Å) C-S(1.82 Å)

42. Shortening the C-heteroatom bond results in an increased 2,4,6- axial interaction. This is particularly pronounced in 1,3-dioxane.

43. 3.5 The Effect of Heteroatoms on conformational Equilibria C-O(1.43 Ao ) and C-N(1.47Ao) heterocycles have shorter bond length and stronger repulsive interaction (1,3-diaxial) An alkyl group located on a carbon a to a heteroatom prefers the equatorial position, which is of course the normally expected behavior, but a polar group in such a location prefers the axial position. Polar Substituent Effect:

44. In 5-alkyl-substituted 1,3-dioxanes, the 5-substituent has a much smaller preference for the equatorial position than in cyclohexane derivatives. This indicates that the lone pairs on the oxygens have a smaller steric requirement than the C-H bonds in the corresponding cyclohexane derivatives. *Cai, J.; Davies, A.G.; Schiesser, C.H. J. Chem. Soc. Perkin Trans. 2 1994, 1151.

45. Anomeric Effect:In pyranose sugars electron withdrawing groups at C(2) prefer axial orientation. NMR spectrum in CDCl3 indicates the all axial conformation is strongly favored. The anomeric effect of a single chlorine is sufficient to drive the equilibrium in favor of the conformation that puts the three acetoxy groups in axial positions. Only form observed by NMR

46. Origin of Anomeric Effect: • VBT: There is a larger dipole-dipole repulsion between the polar bonds at the anomeric carbon in the equatorial conformation.Dipole-dipole interaction between polar bonds at the anomeric carbon is reduced in axial conformation (solvent effect). • b) MOT: Anomeric effect is resulting from an interaction between oxygen LP and the s* orbital of C-2 substituent. When the C-X bond is axial this interaction is possible.

47. The magnitude of the anomeric effect depends on the nature of the substituent and decreases with increasing dielectric constant of the medium. The 2-chloro compound exhibits a significantly greater preference for the axial orientation than the 2-methoxy. The equilibrium constant is larger in CCl4 (e = 22) than in acetonitrile (e= 375). Note:Equilibria between diastereoisomers involving reversible dissociation of the 2-substituent.

49. The anomeric effect of a single chlorine is sufficient to drive the equilibrium in favor of the conformation that puts the three acetoxy groups in axial positions.

50. The C–Cl bond lengths in the molecule shown below are not the same. Which is longer?