1. CHE 240 Unit IV Stereochemistry, Substitution and Elimination Reactions CHAPTER SIX Terrence P. Sherlock Burlington County College 2004

2. Chapter 62 Polarity and Reactivity Halogens are more electronegative than C. Carbon-halogen bond is polar, so carbon has partial positive charge. Carbon can be attacked by a nucleophile. Halogen can leave with the electron pair. =>

3. Chapter 63 Classes of Alkyl Halides Methyl halides: only one C, CH 3 X Primary: C to which X is bonded has only one C-C bond. Secondary: C to which X is bonded has two C-C bonds. Tertiary: C to which X is bonded has three C-C bonds. =>

4. Chapter 64 Classify These: =>

5. Chapter 65 Dihalides Geminal dihalide: two halogen atoms are bonded to the same carbon Vicinal dihalide: two halogen atoms are bonded to adjacent carbons. =>

6. Chapter 66 IUPAC Nomenclature Name as haloalkane. Choose the longest carbon chain, even if the halogen is not bonded to any of those C’s. Use lowest possible numbers for position. =>

7. Chapter 67 Systematic Common Names Name as alkyl halide. Useful only for small alkyl groups. Name these: =>

8. Chapter 68 “Trivial” Names CH 2 X 2 called methylene halide. CHX 3 is a haloform. CX 4 is carbon tetrahalide. Examples:  CH 2 Cl 2 is methylene chloride  CHCl 3 is chloroform  CCl 4 is carbon tetrachloride. =>

9. Chapter 69 Uses of Alkyl Halides Solvents - degreasers and dry cleaning fluid Reagents for synthesis of other compounds Anesthetic: Halothane is CF 3 CHClBr  CHCl 3 used originally (toxic and carcinogenic) Freons, chlorofluorocarbons or CFC’s  Freon 12, CF 2 Cl 2, now replaced with Freon 22, CF 2 CHCl, not as harmful to ozone layer. Pesticides - DDT banned in U.S. =>

10. Chapter 610 Dipole Moments  = 4.8 x  x d, where  is the charge (proportional to  EN) and d is the distance (bond length) in Angstroms. Electronegativities: F > Cl > Br > I Bond lengths: C-F < C-Cl < C-Br < C-I Bond dipoles: C-Cl > C-F > C-Br > C-I 1.56 D 1.51 D 1.48 D 1.29 D Molecular dipoles depend on shape, too! =>

11. Chapter 611 Boiling Points Greater intermolecular forces, higher b.p.  dipole-dipole attractions not significantly different for different halides  London forces greater for larger atoms Greater mass, higher b.p. Spherical shape decreases b.p. (CH 3 ) 3 CBr CH 3 (CH 2 ) 3 Br 73  C 102  C =>

12. Chapter 612 Densities Alkyl fluorides and chlorides less dense than water. Alkyl dichlorides, bromides, and iodides more dense than water. =>

13. Chapter 613 Halogenation of Alkanes All H’s equivalent. Restrict amount of halogen to prevent di- or trihalide formation Highly selective: bromination of 3  C =>

14. Chapter 614 Allylic Halogenation Allylic radical is resonance stabilized. Bromination occurs with good yield at the allylic position (sp 3 C next to C=C). Avoid a large excess of Br 2 by using N-bromosuccinimide (NBS) to generate Br 2 as product HBr is formed. =>

15. Chapter 615 Reaction Mechanism Free radical chain reaction  initiation, propagation, termination. =>

16. Chapter 616 Substitution Reactions The halogen atom on the alkyl halide is replaced with another group. Since the halogen is more electronegative than carbon, the C-X bond breaks heterolytically and X - leaves. The group replacing X - is a nucleophile. =>

17. Chapter 617 Elimination Reactions The alkyl halide loses halogen as a halide ion, and also loses H + on the adjacent carbon to a base. A pi bond is formed. Product is alkene. Also called dehydrohalogenation (-HX). =>

18. Chapter 618 S N 2 Mechanism Bimolecular nucleophilic substitution. Concerted reaction: new bond forming and old bond breaking at same time. Rate is first order in each reactant. Walden inversion. =>

19. Chapter 619 S N 2 Energy Diagram One-step reaction. Transition state is highest in energy. =>

20. Chapter 620 Uses for S N 2 Reactions Synthesis of other classes of compounds. Halogen exchange reaction. =>

21. Chapter 621 S N 2: Nucleophilic Strength Stronger nucleophiles react faster. Strong bases are strong nucleophiles, but not all strong nucleophiles are basic. =>

22. Chapter 622 Trends in Nuc. Strength Of a conjugate acid-base pair, the base is stronger: OH - > H 2 O, NH 2 - > NH 3 Decreases left to right on Periodic Table. More electronegative atoms less likely to form new bond: OH - > F -, NH 3 > H 2 O Increases down Periodic Table, as size and polarizability increase: I - > Br - > Cl - =>

23. Chapter 623 Polarizability Effect =>

24. Chapter 624 Bulky Nucleophiles Sterically hindered for attack on carbon, so weaker nucleophiles. =>

25. Chapter 625 Solvent Effects (1) Polar protic solvents (O-H or N-H) reduce the strength of the nucleophile. Hydrogen bonds must be broken before nucleophile can attack the carbon. =>

26. Chapter 626 Solvent Effects (2) Polar aprotic solvents (no O-H or N-H) do not form hydrogen bonds with nucleophile Examples: =>

27. Chapter 627 Crown Ethers Solvate the cation, so nucleophilic strength of the anion increases. Fluoride becomes a good nucleophile. =>

28. Chapter 628 S N 2: Reactivity of Substrate Carbon must be partially positive. Must have a good leaving group Carbon must not be sterically hindered. =>

29. Chapter 629 Leaving Group Ability Electron-withdrawing Stable once it has left (not a strong base) Polarizable to stabilize the transition state. =>

30. Chapter 630 Structure of Substrate Relative rates for S N 2: CH 3 X > 1° > 2° >> 3° Tertiary halides do not react via the S N 2 mechanism, due to steric hindrance. =>

31. Chapter 631 Stereochemistry of S N 2 Walden inversion =>

32. Chapter 632 S N 1 Reaction Unimolecular nucleophilic substitution. Two step reaction with carbocation intermediate. Rate is first order in the alkyl halide, zero order in the nucleophile. Racemization occurs. =>

33. Chapter 633 S N 1 Mechanism (1) Formation of carbocation (slow) =>

34. Chapter 634 S N 1 Mechanism (2) Nucleophilic attack => Loss of H + (if needed)

35. Chapter 635 S N 1 Energy Diagram Forming the carbocation is endothermic Carbocation intermediate is in an energy well. =>

36. Chapter 636 Rates of S N 1 Reactions 3° > 2° > 1° >> CH 3 X  Order follows stability of carbocations (opposite to S N 2)  More stable ion requires less energy to form Better leaving group, faster reaction (like S N 2) Polar protic solvent best: It solvates ions strongly with hydrogen bonding. =>

37. Chapter 637 Stereochemistry of S N 1 Racemization: inversion and retention =>

38. Chapter 638 Rearrangements Carbocations can rearrange to form a more stable carbocation. Hydride shift: H - on adjacent carbon bonds with C +. Methyl shift: CH 3 - moves from adjacent carbon if no H’s are available. =>

39. Chapter 639 Hydride Shift =>

40. Chapter 640 Methyl Shift =>

41. Chapter 641 S N 2 or S N 1? Primary or methyl Strong nucleophile Polar aprotic solvent Rate = k[halide][Nuc] Inversion at chiral carbon No rearrangements Tertiary Weak nucleophile (may also be solvent) Polar protic solvent, silver salts Rate = k[halide] Racemization of optically active compound Rearranged products =>

42. Chapter 642 E1 Reaction Unimolecular elimination Two groups lost (usually X - and H + ) Nucleophile acts as base Also have S N 1 products (mixture) =>

43. Chapter 643 E1 Mechanism Halide ion leaves, forming carbocation. Base removes H + from adjacent carbon. Pi bond forms. =>

44. Chapter 644 A Closer Look =>

45. Chapter 645 E1 Energy Diagram Note: first step is same as S N 1 =>

46. Chapter 646 E2 Reaction Bimolecular elimination Requires a strong base Halide leaving and proton abstraction happens simultaneously - no intermediate. =>

47. Chapter 647 E2 Mechanism =>

48. Chapter 648 Saytzeff’s Rule If more than one elimination product is possible, the most-substituted alkene is the major product (most stable). R 2 C=CR 2 >R 2 C=CHR>RHC=CHR>H 2 C=CHR tetra > tri > di > mono => minor major

49. Chapter 649 E2 Stereochemistry =>

50. Chapter 650 E1 or E2? Tertiary > Secondary Weak base Good ionizing solvent Rate = k[halide] Saytzeff product No required geometry Rearranged products Tertiary > Secondary Strong base required Solvent polarity not important Rate = k[halide][base] Saytzeff product Coplanar leaving groups (usually anti) No rearrangements =>

51. Chapter 651 Substitution or Elimination? Strength of the nucleophile determines order: Strong nuc. will go S N 2 or E2. Primary halide usually S N 2. Tertiary halide mixture of S N 1, E1 or E2 High temperature favors elimination. Bulky bases favor elimination. Good nucleophiles, but weak bases, favor substitution. =>

52. Chapter 652 Secondary Halides? Mixtures of products are common. =>

53. Chapter 653

54. Chapter 654 POWER POINT IMAGES FROM “ORGANIC CHEMISTRY, 5 TH EDITION” L.G. WADE ALL MATERIALS USED WITH PERMISSION OF AUTHOR PRESENTATION ADAPTED FOR BURLINGTON COUNTY COLLEGE ORGANIC CHEMISTRY COURSE BY: ANNALICIA POEHLER STEFANIE LAYMAN CALY MARTIN