1. Chapter 23Aryl Halides

2. 23.1Bonding in Aryl Halides

3. Aryl Halides • Aryl halides are halides in which the halogen is attached directly to an aromatic ring. • Carbon-halogen bonds in aryl halides are shorter and stronger than carbon-halogen bonds in alkyl halides.

4. H2C CHX X Table 23.1: C—H and C—Cl Bond Dissociation Energies of Selected Compounds Bond Energy:kJ/mol (kcal/mol) X = H X = Cl CH3CH2X sp3 410 (98) 339 (81) sp2 452 (108) 368 (88) sp2 469 (112) 406 (97)

5. Aryl Halides • Aryl halides are halides in which the halogen is attached directly to an aromatic ring. • Carbon-halogen bonds in aryl halides are shorter and stronger than carbon-halogen bonds in alkyl halides. • Because the carbon-halogen bond is stronger, aryl halides react more slowly than alkyl halides when carbon-halogen bond breaking is rate determining.

6. 23.2Sources of Aryl Halides

7. Preparation of Aryl Halides • Halogenation of arenes (Section 12.5) • The Sandmeyer reaction (Section 22.17) • The Schiemann reaction (Section 22.17) • Reaction of aryl diazonium salts with iodide ion (Section 22.18)

8. 23.3Physical Properties of Aryl Halides

9. Cl Cl Physical Properties of Aryl Halides • resemble alkyl halides • all are essentially insoluble in water • less polar than alkyl halides  2.2 D  1.7 D

10. 23.4Reactions of Aryl Halides:A Review and a Preview

11. Reactions of Aryl Halides • Electrophilic Aromatic Substitution (Section 12.14) • Formation of aryl Grignard reagents (Section 14.4) • We have not yet seen any nucleophilic substitution reactions of aryl halides. Nucleophilic substitution on chlorobenzene occurs so slowly that forcing conditions are required.

12. 1. NaOH, H2O 370°C Cl OH 2. H+ Example (97%)

13. – + + Cl Cl Reasons for Low Reactivity • SN1 not reasonable because: • 1) C—Cl bond is strong; therefore, ionization to a carbocation is a high-energy process • 2) aryl cations are less stable than alkyl cations

14. Reasons for Low Reactivity • SN2 not reasonable because ring blocks attack of nucleophile from side opposite bond to leaving group

15. 23.5Nucleophilic Substitution inNitro-Substituted Aryl Halides

16. Cl OCH3 NO2 NO2 But... • nitro-substituted aryl halides do undergonucleophilic aromatic substitution readily CH3OH + + NaOCH3 NaCl 85°C (92%)

17. Cl Cl Cl Cl NO2 O2N NO2 NO2 NO2 NO2 7 x 1010 2.4 x 1015 Effect of nitro group is cumulative • especially when nitro group is ortho and/orpara to leaving group 1.0 too fast to measure

18. Kinetics • follows second-order rate law: rate = k[aryl halide][nucleophile] • inference: both the aryl halide and the nucleophile are involved in rate-determining step

19. X NO2 Effect of leaving group • unusual order: F > Cl > Br > I X Relative Rate* F 312 Cl 1.0 Br 0.8 I 0.4 *NaOCH3, CH3OH, 50°C

20. General Conclusions About Mechanism • bimolecular rate-determining step in whichnucleophile attacks aryl halide • rate-determining step precedes carbon-halogenbond cleavage • rate-determining transition state is stabilized byelectron-withdrawing groups (such as NO2)

21. 23.6The Addition-Elimination Mechanismof Nucleophilic Aromatic Substitution

22. Addition-Elimination Mechanism • Two step mechanism: • Step 1) nucleophile attacks aryl halide and bonds to the carbon that bears the halogen(slow: aromaticity of ring lost in this step) • Step 2) intermediate formed in first step loses halide (fast: aromaticity of ring restored in this step)

23. F OCH3 NO2 NO2 Reaction CH3OH + + NaOCH3 NaF 85°C (93%)

24. – •• •• F OCH3 •• •• •• •• H H H H NO2 Mechanism Step 1 • bimolecular • consistent with second-order kinetics; first order in aryl halide, first order in nucleophile

25. – •• •• •• •• F OCH3 •• •• •• OCH3 F •• •• •• •• H H H H •• – slow H H H H NO2 NO2 Mechanism Step 1

26. •• •• OCH3 F •• •• •• Mechanism • intermediate is negatively charged • formed faster when ring bears electron-withdrawing groups such as NO2 H H – •• H H NO2

27. •• •• OCH3 F •• •• •• H H – •• H H N •• O O + •• •• – •• •• Stabilization of Rate-Determining Intermediateby Nitro Group

28. •• •• •• •• OCH3 OCH3 F F •• •• •• •• •• •• H H H H – •• H H H H N N •• •• •• O O O O + + •• •• •• •• – – – •• •• •• •• Stabilization of Rate-Determining Intermediateby Nitro Group

29. •• •• OCH3 F •• •• •• Mechanism Step 2 H H – •• H H NO2

30. – •• •• F •• •• •• •• OCH3 •• •• OCH3 F •• •• •• H H – •• H H NO2 NO2 Mechanism Step 2 H H fast H H

31. Leaving Group Effects F > Cl > Br > I is unusual, but consistentwith mechanism • carbon-halogen bond breaking does not occuruntil after the rate-determining step • electronegative F stabilizes negatively charged intermediate

32. 23.7Related Nucleophilic AromaticSubstitution Reactions

33. F OCH3 F F F F NaOCH3 CH3OH F F F F 65°C F F Example: Hexafluorobenzene • Six fluorine substituents stabilize negatively charged intermediate formed in rate-determining step and increase rate of nucleophilic aromatic substitution. (72%)

34. Cl OCH3 N N Example: 2-Chloropyridine • 2-Chloropyridine reacts 230,000,000 times faster than chlorobenzene under these conditions. NaOCH3 CH3OH 50°C

35. – •• OCH3 •• •• Cl N •• Example: 2-Chloropyridine • Nitrogen is more electronegative than carbon, stabilizes the anionic intermediate, and increases the rate at which it is formed.

36. – •• OCH3 •• •• •• OCH3 •• Cl N •• Example: 2-Chloropyridine • Nitrogen is more electronegative than carbon, stabilizes the anionic intermediate, and increases the rate at which it is formed. •• – N Cl ••

37. 23.8The Elimination-Addition Mechanismof Nucleophilic Aromatic Substitution:Benzyne

38. Cl NH2 Aryl Halides Undergo Substitution WhenTreated With Very Strong Bases KNH2, NH3 –33°C (52%)

39. CH3 CH3 CH3 Br NH2 NH2 Regiochemistry • new substituent becomes attached to eitherthe carbon that bore the leaving group orthe carbon adjacent to it NaNH2,NH3 + –33°C

40. CH3 CH3 CH3 NaNH2, NH3 –33°C NH2 Br NH2 Regiochemistry • new substituent becomes attached to eitherthe carbon that bore the leaving group orthe carbon adjacent to it +

41. CH3 Cl CH3 CH3 CH3 NH2 NH2 NH2 Regiochemistry NaNH2, NH3 –33°C + +

42. * Cl KNH2, NH3 –33°C NH2 * NH2 * Same result using 14C label + (52%) (48%)

43. H •• H Cl •• •• – NH2 •• H H •• H Mechanism Step 1

44. H H – •• •• Cl H Cl •• H •• •• •• •• – NH2 •• H H H •• NH2 H •• H H Mechanism Step 1 • compound formed in this step is called benzyne

45. H H H H Benzyne • Benzyne has a strained triple bond. • It cannot be isolated in this reaction, but is formed as a reactive intermediate.

46. H H – NH2 •• •• H H Mechanism Step 2

47. H H – H H – •• NH2 •• •• NH2 H H •• H H Mechanism Step 2 • Angle strain is relieved. The two sp-hybridized ring carbons in benzyne become sp2 hybridized in the resulting anion.

48. NH2 H H •• H H H Mechanism Step 3 – •• NH2 ••

49. – NH2 NH2 H H H •• •• •• H H H H NH2 H •• H H Mechanism Step 3 – •• NH2 ••

50. * Cl OH * OH * Hydrolysis of Chlorobenzene • 14C labeling indicates that the high-temperature reaction of chlorobenzene with NaOH goes via benzyne. NaOH, H2O 395°C + (43%) (54%)