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Chapter 12 Notes

Aromatic Substitution

Electrophilic Aromatic Substitution  benzene can be made to react with very strong electrophiles (E+)  intermediate is a carbocation (like addition to one of the pi bonds)  nucleophiles don't add to the cation (H+ leaves, regenerates benzene ring)  reaction is substitution (E+ for H+) Mechanism of Aromatic Substitution

Mechanism - why slower than alkenes ?  Ea for electrophilic attack on benzene is greater than Ea for electrophilic attack on an alkene  although the cation intermediate is delocalized and more stable than an alkyl cation, benzene is much more stable than an alkene Mechanism - why substitution ?  the substitution product regains the aromatic stability  an addition product would be a conjugated diene, not as stable

Bromination of Benzene  electrophile is Br+  generated from Br2 + FeBr3

Chlorination of Benzene  electrophile is Cl+  generated from Cl2 + FeCl3

Nitration of Benzene  electrophile is NO2+  generated from H2SO4 + HNO3

Sulfonation of Benzene  electrophile is HSO3+  generated from H2SO4 + SO3

Friedel-Crafts Alkylation  electrophile is an alkyl cation (R+)  generated from RCl + AlCl3

 limitations of the Friedel-Crafts reaction o cation rearrangements may occur o doesn't work with deactivated aromatic rings  extensions of the Friedel-Crafts reaction o other sources of cations, e.g., alkene + H+ Friedel-Crafts Acylation  electrophile is an acyl cation (RCO+)  generated from RCOCl + AlCl3  acyl chlorides prepared from RCOOH + SOCl2

 Clemmensen reduction: Zn(Hg) / HCl - reduces C=O to CH2  Wolff-Kishner reduction: NH2NH2 / KOH / 180° - reduces C=O to CH2  acylation followed by reduction makes primary alkylbenzenes without rearrangement Substituent Effects  substituents on the benzene ring can affect the reaction in two ways: reactivity - substituted benzene may react faster or slower than benzene itself reacts orientation - the new group may be oriented ortho, meta, or para with respect to the original substituent Reactivity Effects  activating - reaction is faster observed with electron-donating groups that make the ring more electronrich  deactivating - reaction is slower observed with electron-withdrawing groups that make the ring less electron-rich Orientation Effects

 substituent already present on the benzene ring determines the location of the new group  ortho,para-directors: electron-donating groups direct the new group mainly to ortho & para  meta-directors: electron-withdrawing groups direct new group mainly meta Ortho, Para Directors  the best cation is formed when the electrophile adds either ortho or para (better than unsubstituted)

Meta Directors  the best cation is formed when the electrophile adds meta (but this is worse than unsubstituted)

Classifying Substituents  see Table 12.2  activating and o,p-directing: alkyl, aryl, O and N groups  deactivating and m-directing: N+ groups, polar multiple bonds  deactivating but o,p-directing: the halogens (F, Cl, Br, I) (electron-withdrawing atoms, but lone pairs can stabilize the cation when it is ortho or para) Partial Rate Factors  rate of reaction at one position relative to benzene  activating and o,p-directing: CH3 : o= 42 , m = 2.5 , p = 58

 deactivating and m-directing: CF3 : o = 0.0000045 , m = 0.000067 , p = 0.0000045  deactivating but o,p-directing: Cl : o = 0.029 , m = 0.0009 , p = 0.137 Synthetic Strategy  synthesis of complex compounds requires attention to the order in which groups are attached  retrosynthetic analysis - think backwards one step at a time (What reaction could have made this target compound?) Synthesis Example  target compound: p-nitrobenzoic acid  note both substituents are m-directors

Synthesis Example

Substitution on Other Aromatic Systems  naphthalene - 1-position (activated)  furan, pyrrole, thiophene - 2-position (activated)  pyridine - 3-position (deactivated) Aryl Halides - Bonding  resonance electron donation to aromatic ring makes C-X bond stronger and less polar  substitution reactions don't occur readily via SN1 or SN2 mechanisms Aromatic Nucleophilic Substitution - addition/elimination mechanism

 addition of nucleophile to an aryl halide ( at the ipso position )  intermediate is a delocalized anion, analogous to the cation in electrophilc substitution  usually works only with strong electron-withdrawing groups ortho & para (e.g., nitro)  loss of leaving group returns the aromaticity

Aromatic Nucleophilic Substitution - elimination/addition (benzyne) mechanism  elimination from an aryl halide with a very strong base (usually NaNH2 in NH3)  intermediate is benzyne, highly reactive  benzyne adds nucleophiles, e.g., NH3  note different substitution patterns that can result

 benzyne also reacts in Diels-Alder reactions as a dienophile...