Electrophilic Aromatic Substitution

Transcription

1 Electrophilic Aromatic Substitution E δ δ E Y Y

2 E δ δ E Y Y Electrophilic aromatic substitutions include: Nitration Sulfonation alogenation Friedel-Crafts Alkylation Friedel-Crafts Acylation

3 Nitration of Benzene 2 SO 4 ONO 2 NO 2 2 O Nitrobenzene (95%)

4 Sulfonation of Benzene OSO 2 O heat SO 2 O 2 O Benzenesulfonic acid (100%)

5 alogenation of Benzene Br 2 FeBr 3 Br Br Bromobenzene (65-75%)

6 Friedel-Crafts Alkylation of Benzene (C 3 ) 3 CCl AlCl 3 C(C 3 ) 3 Cl tert-butylbenzene (60%)

7 Friedel-Crafts Acylation of Benzene O C 3 C 2 CCl AlCl 3 O CC 2 C 3 Cl 1-Phenyl-1-propanone (88%)

8 Mechanistic Principles of Electrophilic Aromatic Substitution

9 Step 1: attack of electrophile on π-electron system of aromatic ring E E highly endothermic carbocation is allylic, but not aromatic

10 Step 2: loss of a proton from the carbocation intermediate E E highly exothermic this step restores aromaticity of ring

11 E E E

12 Based on this general mechanism: what remains is to identify the electrophile in nitration, sulfonation, halogenation, Friedel- Crafts alkylation, and Friedel-Crafts acylation to establish the mechanism of specific electrophilic aromatic substitutions

13 Nitration of Benzene

14 Nitration of Benzene 2 SO 4 ONO 2 NO 2 2 O Electrophile is nitronium ion O N O

15 Step 1: attack of nitronium cation on π-electron system of aromatic ring NO 2 NO 2

16 Step 2: loss of a proton from the carbocation intermediate NO 2 NO 2

17 Where does nitronium ion come from? O N O 2 SO 4 O N O O O O N O O

18 Sulfonation of Benzene

19 Sulfonation of Benzene OSO 2 O heat SO 2 O 2 O Several electrophiles present: a major one is sulfur trioxide O S O O

20 Step 1: attack of sulfur trioxide on π-electron system of aromatic ring SO 3 SO 3

21 Step 2: loss of a proton from the carbocation intermediate SO 3 SO 3

22 Step 3: protonation of benzenesulfonate ion 2 SO 4 SO 3 SO 3

23 alogenation of Benzene

24 alogenation of Benzene Br 2 FeBr 3 Br Br Electrophile is a Lewis acid-lewis base complex between FeBr 3 and Br 2.

25 The Br 2 -FeBr 3 Complex Br Br FeBr 3 Br Br FeBr 3 Lewis base Lewis acid Complex The Br 2 -FeBr 3 complex is more electrophilic than Br 2 alone.

26 Step 1: attack of Br 2 -FeBr 3 complex on π-electron system of aromatic ring Br Br FeBr 3 Br FeBr 4

27 Step 2: loss of a proton from the carbocation intermediate Br Br

28 Friedel-Crafts Alkylation of Benzene

29 Friedel-Crafts Alkylation of Benzene (C 3 ) 3 CCl AlCl 3 C(C 3 ) 3 Cl Electrophile is tert-butyl cation 3 C 3 C C C 3

30 Role of AlCl 3 acts as a Lewis acid to promote ionization of the alkyl halide (C 3 ) 3 C Cl AlCl 3 (C 3 ) 3 C Cl AlCl 3 (C 3 ) 3 C Cl AlCl 3

31 Step 1: attack of tert-butyl cation on π-electron system of aromatic ring C(C 3 ) 3 C(C 3 ) 3

32 Step 2: loss of a proton from the carbocation intermediate C(C 3 ) 3 C(C 3 ) 3

33 Rearrangements in Friedel-Crafts Alkylation Carbocations are intermediates. Therefore, rearrangements can occur The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. (C 3 ) 2 CC 2 Cl AlCl 3 C(C The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. 3 ) 3 Isobutyl chloride tert-butylbenzene (66%)

34 Rearrangements in Friedel-Crafts Alkylation Isobutyl chloride is the alkyl halide. But tert-butyl cation is the electrophile. (C 3 ) 2 CC 2 Cl AlCl 3 C(C The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. 3 ) 3 Isobutyl chloride tert-butylbenzene (66%)

35 Rearrangements in Friedel-Crafts Alkylation 3 C C C 2 Cl AlCl 3 C 3 3 C C C 2 Cl AlCl 3 C 3

36 Reactions Related to Friedel-Crafts Alkylation 2 SO 4 Cyclohexylbenzene (65-68%) Cyclohexene is protonated by sulfuric acid, giving cyclohexyl cation which attacks the benzene ring

37 Friedel-Crafts Acylation of Benzene

38 Friedel-Crafts Acylation of Benzene O C 3 C 2 CCl AlCl 3 O CC 2 C 3 Cl Electrophile is an acyl cation C 3 C 2 C O C 3 C 2 C O

39 Step 1: attack of the acyl cation on π-electron system of aromatic ring O O CC 2 C 3 CC 2 C 3

40 Step 2: loss of a proton from the carbocation intermediate O O CC 2 C 3 CC 2 C 3

41 Acid Anhydrides can be used instead of acyl chlorides O O AlCl 3 C 3 COCC 3 O CC 3 Acetophenone (76-83%) O C 3 CO

42 Acylation-Reduction

43 Acylation-Reduction permits primary alkyl groups to be attached to an aromatic ring O RCCl O CR AlCl 3 Zn(g), Cl Reduction of aldehyde and ketone carbonyl groups using Zn(g) and Cl is called the Clemmensen reduction. C 2 R

44 Acylation-Reduction permits primary alkyl groups to be attached to an aromatic ring O RCCl AlCl 3 Reduction of aldehyde and ketone carbonyl groups by heating with 2 NN 2 and KO is called the Wolff-Kishner reduction. O CR 2 NN 2, KO, triethylene glycol, heat C 2 R

45 Example: Prepare isobutylbenzene (C 3 ) 2 CC 2 Cl C 2 C(C 3 ) 3 AlCl 3 No! Friedel-Crafts alkylation of benzene using isobutyl chloride fails because of rearrangement.

46 Recall (C 3 ) 2 CC 2 Cl AlCl 3 C(C 3 ) 3 Isobutyl chloride tert-butylbenzene (66%)

47 Use Acylation-Reduction Instead O (C 3 ) 2 CCCl AlCl 3 O Zn(g) Cl C 2 C(C 3 ) 3 CC(C 3 ) 2