Chapter 17 Aromatic Substitutions Organic Chemistry II Fall 1999 Chapter 17 Aromatic Substitutions electrophilic aromatic substitutions: E+ mechanism: arenium ion,  672 Figure 17.1 loss of aromaticity: higher DE,  673 Figure 17.2 nitration: nitrobenzene (mixed acid);  673 bot. formation of a nitronium ion (+NO2):  674 Figure 17.3 OrgChem-Chap17 Chapter 18

Effect of Substituents (I) Organic Chemistry II Fall 1999 Effect of Substituents (I) effect on the reaction rate & regioselectivity toluene: 17 times faster & ortho/para,  674 bottom stabilized resonance for ortho/para-substitution stabilized OrgChem-Chap17 Chapter 18

Effect of Substituents (II) Organic Chemistry II Fall 1999 Effect of Substituents (II) oxygen (amine): 104 faster;  676 e--donating (resonance) >> e--withdrawing (inductive) nitrobenzene: 1017 slower & meta;  678 top practice:  677-678 Problem 17.1-17.4 destabilized OrgChem-Chap17 Chapter 18

Effect of Substituents (III) Organic Chemistry II Fall 1999 Effect of Substituents (III) chlorine: 17 times slower & ortho/para,  679 e--donating (resonance) < e--withdrawing (inductive) general substituent effect:  680 Table 17.1 statistics vs steric effect:  681 bottom (~1:4) toluene (~2:1,  674); anisole (~1:2,  676) multiple substituents: dominating group,  682 practice:  683 Problem 17.7-17.8 OrgChem-Chap17 Chapter 18

Nitration: Aniline Derivatives Organic Chemistry II Fall 1999 Nitration: Aniline Derivatives nitrating reagents: HNO3 & H+  683-684 H+: anhyd. HNO3, H2SO4 (mixed acid), CF3CO2H, CF3SO3H, NO2+BF4-, N2O4 / O3 or O2 (cat.), AcOH reduction to amine: aniline;  710 top dinitration: vigorous conditions,  684 middle nitration of aniline: ammonium ion,  684 bot. protection to amides: activating, o-/p-,  685 bot. OrgChem-Chap17 Chapter 18

Halogenation / Sulfonation Organic Chemistry II Fall 1999 Halogenation / Sulfonation less reactive arenes: formation of Cl+ or Br+ Lewis acid catalyst: AlX3 or FeX3,  686 bottom activated arenes: Cl2 or Br2 (no catalyst) mesitylene/aniline (disubstitution):  687 bottom controlled monosubstitution:  688 top sulfonation: SO3, (H2SO4);  689 top reversible: heating with H3O+;  689 bottom OrgChem-Chap17 Chapter 18

Friedel-Crafts Alkylation Organic Chemistry II Fall 1999 Friedel-Crafts Alkylation carbocations (E+): alkyl halides/Lewis acids mechanism: SN1 type,  690-691 Figure 17.4 other carbocations: alcohols/alkenes & acids,  856-7 limitations: multiple alkylation; no reaction with deactivating groups; rearrangement,  692 top useful intramolecular alkylation: bicylics;  692 middle synthetic detergents, BHT & BHA:  694-6 Focus On practice:  692-3 Problem 17.14, 17.15 & 17.16 OrgChem-Chap17 Chapter 18

Friedel-Crafts Acylation Organic Chemistry II Fall 1999 Friedel-Crafts Acylation acylium ion (E+): mechanism,  696 bottom more useful: reaction with weakly deactivated arenes, no rearrangements, no multiple substitution anhydrides as well as acyl chlorides:  697 top more para isomer:  697 bottom intramolecular cyclization: polycyclics;  698 top electrophilic substitution of polycyclic arenes more reactive than benzene:  699 bottom regioselectivity: C-1 (kinetic) vs C-2 (thermodynamic) OrgChem-Chap17 Chapter 18

Selectivity of Polycyclic Arenes (I) Organic Chemistry II Fall 1999 Selectivity of Polycyclic Arenes (I) substitution at C-1: 7 resonances, more stable OrgChem-Chap17 Chapter 18

Selectivity of Polycyclic Arenes (II) Organic Chemistry II Fall 1999 Selectivity of Polycyclic Arenes (II) substitution at C-2: 6 resonances, less stable OrgChem-Chap17 Chapter 18

Nucleophilic Aromatic Substitution Organic Chemistry II Fall 1999 Nucleophilic Aromatic Substitution diazonium ions: mechanism,  700 bottom substitution of N2: I / F / OH / H;  701-702 Sandmeyer reaction: CuX (X=Cl, Br, CN) addition-elimination:  704 Figure 17.5 EWG & rate (F > Cl > Br > I):  705 top elimination-addition:  707 Figure 17.6 benzyne:  706 mid &  707-9 Evidences practice:  702-708 Problem 17.23-17.26 OrgChem-Chap17 Chapter 18

Synthesis of Aromatic Compounds Organic Chemistry II Fall 1999 Synthesis of Aromatic Compounds nitro (NO2)  amine (NH2):  710 top C=O  CH2: Clemmensen,  710 bot. / Wolff-Kishner,  711 top / catalytic H2,  711 middle useful for arenes substituted with primary alkyl groups CHRR’  CO2H:  711 bottom & 712 top practice:  712 Problem 17.27-17.28 summary of the reactions:  713 Figure 17.7 practice: m- / p-chloronitrobenzene,  714 top; o-bromophenol,  714 bot.; m-bromochlorobenzene,  715 top; m-bromotoluene,  715 bottom OrgChem-Chap17 Chapter 18