CHM030 5.2: Reactions of Aromatic Compounds

• electrophilic aromatic substitution


  most common reaction of aromatic compounds
• electrophilic aromatic substitution


  a process in which an electrophile (E+) reacts with an aromatic ring and substitutes for one of the hydrogen atoms

  
• Electrophilic Aromatic Substitution Reactions: Mechanism

  Step 1: Attack on the electrophile forms the sigma complex

  Step 2: Loss of a proton gives the substitution product
• Electrophilic Aromatic Substitution Reactions (SAHAN)

  Halogenation (-X)

  Nitration (-NO2)

  Sulfonation (-SO3H)

  Alkylation (-R)

  Acylation (-R-C=O)
• Ferric Bromide (FeBr3)


  The catalyst needed to react molecular bromine (Br2) with benzene
• FeBr3


  • a Lewis acid
  • accepts an electron pair from Br2 and thereby puts a strong positive charge on the end bromine atom
  • basically turns the weaker electrophile, Br2 , into the stronger electrophile, Br+
• Electrophilic Aromatic Substitution Reactions: Bromination

  • the electrophilic Br+ then reacts with the electron-rich (nucleophilic) benzene ring to yield a non-aromatic carbocation intermediate.
  • this carbocation is doubly allylic and is a hybrid of three resonance forms.
• Electrophilic Aromatic Substitution Reactions : Bromination

  • the intermediate in electrophilic aromatic substitution is much less stable than the starting benzene ring itself
  • the reaction of an electrophile with a benzene ring has a relatively high activation energy and is rather slow
• Energy Diagram of Electrophilic Bromination of Benzene

  the reaction occurs in two steps and releases energy
• Ferric Chloride (FeCl3)


  The catalyst needed to react molecular chlorine (Cl2) with benzene
• loratadine


  anti-allergy

  
• diazepam


  valium

  
• Cu+2


  the catalyst needed to react molecular iodine (I2) with benzene
• the combination of nitric acid and sulfuric acid produces the electrophile NO2+ (nitronium ion)
• NO2+

  • the combination of nitric acid and sulfuric acid produces the electrophile NO2+ (nitronium ion)
  • NO2+ is an electrophile formed from HNO3 by protonation and loss of water
• aromatic sulfonation


  a key step in the synthesis of such compounds as the sulfa drug family of antibiotics
• Electrophilic Aromatic Substitution Reactions: Sulfonation

  • aromatic rings are sulfonated by reaction with sulfuric acid, a mixture of SO3 and H2SO4
  • the reactive electrophile is HSO3+ and substitution occurs with the usual two-step mechanism seen for bromination

  
• Friedel-Crafts alkylation 


  this reaction is the substitution of an alkyl group R+ for an aromatic H+ in the benzene ring
• The Friedel-Crafts Alkylation Reaction

  • the reaction is carried out by treating the aromatic compound with an alkyl chloride, RCl, in the presence of AlCl3 to generate a carbocation electrophile, R+
• The Friedel-Crafts Alkylation Reaction

  • AlCl3 , a Lewis acid catalyst, promotes the formation of the carbocation R + by helping the alkyl halide to dissociate
  • loss of H+ completes the reaction
• Mechanism of the Friedel–Crafts alkylation Reaction

  the electrophile is a carbocation, generated by AlCl3 - assisted ionization of an alkyl chloride

  
• The Friedel-Crafts Acylation Reaction

  The reaction of a carboxylic acid chloride (RCOCl) with an aromatic ring in the presence of AlCl3 catalyst substitutes an H+ in the aromatic ring with an acyl group, R-C=O
• acetophenone


  benzene reacts with acetyl chloride and yields _
• The Friedel-Crafts Acylation Reaction: Mechanism

  • Similar to Friedel-Crafts alkylation
  • Reactive electrophile: resonance-stabilized acyl cation
  • An acyl cation does not rearrange
• What effects does a substituent already present on a benzene ring have on the electrophilic substitution of a second group?

  • substituents affect the reactivity of an aromatic ring
• Substituent Effects in Electrophilic Aromatic Substitution

  • substituents can cause a compound to be more or less reactive than benzene
• Substituent Effects in Electrophilic Aromatic Substitution

  substituents affect the orientation of the reaction – the positional relationship is controlled by ortho- and para-directing activators, ortho- and para-directing deactivators, and meta-directing deactivators

  
• Substituent Effects in Electrophilic Aromatic Substitution: Reactivity

  In aromatic nitration:

  • the presence of an ‒OH substituent makes the ring 1000 times more reactive than benzene
  • the presence of an ‒NO2 substituent makes the ring more than 10 million times less reactive than benzene

  
• Substituent Effects in Electrophilic Aromatic Substitution: Orientation

  • an ‒OH group directs further substitution toward the ortho and para positions
  • a ‒CN directs further substitution primarily toward the meta position
• activating substituents

  • activate a benzene ring towards further substitution by donating electron density into the aromatic ring
• Activating Substituents: Reactivity

  Donating electron density into the ring increases the reaction rate by stabilizing the intermediate carbocation
• deactivating substituents 


  deactivate a benzene ring towards further substitution by withdrawing electron density from the aromatic ring
• Deactivating Substituents: Reactivity

  withdrawing electron density from the ring decreases the reaction rate by destabilizing the intermediate carbocation
• An Explanation of Substituent Effects

  The common characteristic of all activating groups is that they donate electrons to the ring, thereby making the ring more electron-rich, stabilizing the carbocation intermediate, and lowering the activation energy for its formation.
• An Explanation of Substituent Effects

  The common characteristic of all deactivating groups is that they withdraw electrons from the ring, thereby making the ring more electron-poor, destabilizing the carbocation intermediate, and raising the activation energy for its formation.
• Activating and Deactivating Effects in Aromatic Rings

  Electron donation or withdrawal may occur either by an inductive effect or a resonance effect.
• inductive effect


  the withdrawal or donation of electrons through a σ bond due to an electronegativity difference between the ring and the attached substituent atom
• resonance effect 


  the withdrawal or donation of electrons through a π bond due to the overlap of a p orbital on the substituent with a p orbital on the aromatic ring
• Orienting Effects in Aromatic Rings: Ortho and Para Directors

  Nitration of Phenol: The ortho and para intermediates are more stable than the meta intermediate because they have more resonance forms, including a particularly favorable one that involves electron donation from the oxygen atom.
• Orienting Effects in Aromatic Rings: Meta Directors

  Chlorination of benzaldehyde: The meta intermediate is more favorable than ortho and para intermediates because it has three favorable resonance forms rather than two.