10. Organohalides

1. 10. Organohalides

2. Why this Chapter? • Reactions involving organohalides are less frequently encountered than other organic compounds, but reactions such as nucleophilic substitutions/eliminations that they undergo will be encountered • Alkyl halide chemistry is model for mechanistically similar but more complex

3. What Is an Alkyl Halide • An organic compound containing at least one carbon-halogen bond (C-X) • X (F, Cl, Br, I) replaces H • Can contain many C-X bonds • Properties and some uses • Fire-resistant solvents • Refrigerants • Pharmaceuticals and precursors

4. 10.1 Naming Alkyl Halides • Find longest chain, name it as parent chain • (Contains double or triple bond if present) • Number from end nearest any substituent (alkyl or halogen)

5. Number all halogens and list different in alphabetical order.

6. Naming if Two Halides or Alkyl Are Equally Distant from Ends of Chain • Begin at the end nearer the substituent whose name comes first in the alphabet

7. Common Names • Treat halogen as parent with alkyl side group

8. Learning Check: • Give names for the following:

9. Solution: • Give names for the following: Iodobutane (butyl iodide) 1-chloro-3-methylbutane (isopentyl chloride) 1,5-dibromo-2,2-dimethylpentane 1-chloro-3-ethyl-4-iodopentane 2-bromo-5-chlorohexane 1,3-dichloro-3-methylbutane

10. 10.2 Structure of Alkyl Halides • C-X bond is longer as you go down periodic table • C-X bond is weaker as you go down periodic table • C-X bond is polarized with slight positive on carbon and slight negative on halogen

11. 10.3 Preparing Alkyl Halides from Alkenes: • Alkyl halide from addition of HCl, HBr, HI to alkenes to give Markovnikov product (see Alkenes chapter) • Alkyl dihalide from anti addition of bromine or chlorine

12. 10.3 Preparing Alkyl Halides from Alkanes: Radical Halogenation • Alkane + Cl2 or Br2, heat or light replaces C-H with C-X but gives mixtures • Hard to control • Via free radical mechanism • It is usually not a good idea to plan a synthesis that uses this method

13. Radical Halogenation of Alkanes • If there is more than one type of hydrogen in an alkane, reactions favor replacing the hydrogen at the most highly substituted carbons (not absolute) • 1o H’s • 1 3o H So would expect 10:90 ratio if # of H’s was sole factor

14. Relative Reactivity: Chlorination • Based on quantitative analysis of reaction products, relative reactivity is estimated • Order parallels stability of radicals

15. Relative Reactivity: Chlorination 1 3o H 9 1o H’s So would expect 10:90 ratio if # of H’s was sole factor 1 3o H 1 x 5 = 5 9 1o H’s 9 x 1 = 9 So would predict 5:9 ratio Or 5/14 : 9/14 = 35.7: 64.3

16. Learning Check: • Predict ratio of mono-chlorinated butanes

17. Solution: • Predict ratio of mono-chlorinated butanes 6 1o H’s 4 2o H’s 6 1o H’s 6 x 1 = 6 4 2o H’s 4 x 3.5 = 14 So would expect 60:40 ratio if # of H’s was sole factor So would predict 6:14 ratio Or 6/20 : 14/20 = 30: 70

18. Learning Check: How many constitutional isomers will form in the radical mono-chlorination of 2,3-dimethylpentane? • 3 • 4 • 5 • 6 • 7

19. Solution: How many constitutional isomers will form in the radical mono-chlorination of 2,3-dimethylpentane? • 3 • 4 • 5 • 6 • 7

20. Learning Check: The selectivity of chlorine radical is 1.0 : 3.5 : 5.0 for 1°, 2° and 3°hydrogens, respectively. If only monochlorides were to form in the radical chlorination of 1,3-dimethylcyclobutane, what is the expected yield of the tertiary chloride? • 1/6 • 1/5 • 1/4 • 1/3 • 1/2

21. Solution: The selectivity of chlorine radical is 1.0 : 3.5 : 5.0 for 1°, 2° and 3°hydrogens, respectively. If only monochlorides were to form in the radical chlorination of 1,3-dimethylcyclobutane, what is the expected yield of the tertiary chloride? • 1/6 • 1/5 • 1/4 • 1/3 • 1/2

22. Relative Reactivity: Bromination • Reaction distinction is more selective with bromine than chlorine

23. Relative Reactivity: Bromination Formation of C radical more costly with Br. So Br more picky thus more selective.

24. Learning Check: Which of these radicals is expected to be the least selective? • HO• • F• • Cl• • Br• • I•

25. Solution: Which of these radicals is expected to be the least selective? • HO• • F• • Cl• • Br• • I•

26. 10.4,5 Preparing Alkyl Halides from Alkenes: AllylicBromination • Allylic position more reactive • Allylic radical stabilized by resonance

27. Allylic Stabilization • Allyl radical is delocalized • More stable than typical alkyl radical by 40 kJ/mol (9 kcal/mol) • Allylic radical is more stable than tertiary alkyl radical

28. AllylicBromination: NBS • N-bromosuccinimide (NBS) selectively brominates allylic positions • Requires light for activation • A source of dilute bromine atoms

29. AllylicBromination: NBS

30. AllylicBromination: NBS • Product mix favors more substituted C=C and less hindered Br

31. Examples: NBS

32. Use of Allylic Bromination • Allylic bromination with NBS creates an allylic bromide • Reaction of an allylic bromide with base produces a conjugated diene, useful in synthesis of complex molecules

33. Learning Check: • Predict the products of allylicbromination w/ NBS NBS NBS

34. Solution: • Predict the products of allylicbromination w/ NBS NBS NBS

35. 10.6 Preparing Alkyl Halides from Alcohols • Reaction of tertiary C-OH with HX is fast and effective • Add HCl or HBr gas into ether solution of tertiary alcohol • Primary and secondary alcohols react very slowly and often rearrange, so alternative methods are used

36. Example:

37. Alkyl Halides from Alcohols • Alternative methods for slow primary and secondary alcohols to avoid rearrangements.

38. Learning Check: • Prepare the following from alcohols

39. Solution: • Prepare the following from alcohols HCl PBr3 PBr3 HCl

40. 10.7 Reactions of Alkyl Halides: Grignard Reagents • Reaction of RX with Mg in ether or THF • Product is RMgX – an organometallic compound (alkyl-metal bond) • R is alkyl 1°, 2°, 3°, aryl, alkenyl • X = Cl, Br, I

41. Grignard Reagents • Forms a basic/nucleophilic Carbon Example:

42. 10.8 Organometallic Coupling Reactions • Alkyllithium (RLi) forms from RBr and Li metal • RLi reacts with copper iodide to give lithium dialkylcopper (Gilman reagents) • Lithium dialkylcopper reagents react with alkyl halides to give alkanes

43. Examples:

44. Utility of Organometallic Coupling in Synthesis • Coupling of two organometallic molecules produces larger molecules of defined structure • Aryl and vinyl organometallics also effective • Coupling of lithium dialkylcopper molecules proceeds through trialkylcopper intermediate

45. Palladium-catalyzed Tributyltin chloride • Works well with aryl or vinyl halides

46. 10.9 Oxidation and Reduction in Organic Chemistry • In organic chemistry, we say that oxidationoccurs when a carbon or hydrogen that is connected to a carbon atom in a structure is replaced by oxygen, nitrogen, or halogen • Oxidation is a reaction that results in loss of electron density at carbon (as more electronegative atoms replace hydrogen or carbon) • Oxidation = • LEO • Gaining an Oxygen • Or Losing a Hydrogen Oxidation: break C-H (or C-C) and form C-O, C-N, C-X

47. Reduction Reactions • Organic reduction is the opposite of oxidation • Results in gain of electron density at carbon (replacement of electronegative atoms by hydrogen or carbon) • Reduction = • GER • Losing an Oxygen • Or Gaining a Hydrogen Reduction: form C-H (or C-C) and break C-O, C-N, C-X

48. Oxidation Levels • Functional groups are associated with specific levels CH4 -4 -3 -2 0 +2 +4

49. Examples:

50. Examples: