Chapter 17 – Reactions of Aromatic Compounds

  • Electrophilic Aromatic Substitution
  • General reaction - an electrophile replaces a hydrogen
  • Electrons of pi system attack strong electrophile, generating resonance-stabilized carbocation intermediate (sigma complex)

This is the slow step because it breaks up the aromaticity.

  • Loss of a proton restores aromaticity
  • Nitration
  • Generation of the nitronium ion
  • Electrophilic attack
  • Loss of proton
  • Sulfonation
  • SO3 is also a powerful electrophile, but less so.
  • This reaction is reversible – Steam it!
  • Halogenation
  • Bromination
  • Bromine reacts with FeBr3 to form the electrophile
  • Electrophilic attack
  • Loss of proton
  • Chlorination
  • Just like bromination, but you use chlorine and FeCl3
  • Iodination
  • Nitric acid is used as a reagent instead of a metal catalyst to generate I+
  • Friedel-Crafts Alkylation
  • Alkyl choride + AlCl3 form a carbocation-like structure
  • It is important to note that this is likely still complexed with the Lewis acid catalyst.
  • You don’t really get the free carbocation, but it acts as though you do.
  • The carbocation acts as the electrophile
  • Another way to alkylate
  • When you start with an alkene and add a non-nucleophilic acid, you can generate a carbocation.
  • This carbocation can now be the electrophile for Alkylation.
  • Limitations of Friedel-Crafts Alkylation
  • The carbocation can rearrange, so if you’re trying to add a straight chain, this won’t work.
  • Overalkylation
  • We will see that alkyl groups are activators for this reaction, so once you put one alkyl group on the addition of a second alkyl group is even easier.
  • Does not work on deactivated rings.
  • Friedel-Crafts Acylation
  • AlCl3 removes the Cl from an acid chloride
  • This cation is resonance-stabilized, so you really do get it.
  • This is called the acyllium ion and you do need to know its name!
  • The carbonyl and alkyl group add to the ring
  • How Friedel-Crafts Acylation gets over two of the limitations of Alkylation
  • No rearrangement
  • You will not overacylate, because once you put the acyl group on, you have deactivated the ring
  • It still does not work on deactivated rings.

Name of Reaction / Reagents / Electrophile / What Replaces the H
Nitration / HNO3/H2SO4 / Nitronium ion
(NO2+) / NO2
Sulfonation / H2SO4
(SO3 sometimes) / SO3 or HSO3+ / SO3H
Bromination / Br2, FeBr3 / “Br+” / Br
Chlorination / Cl2, FeCl3 / “Cl+” / Cl
Iodination / I2, HNO3 / I+ / I
Alkylation / RCl/AlCl3 or RBr/FeBr3 / “R+” / R
Acylation / Acid chloride/ AlCl3 / Acyllium ion
/
  • Substituent Effects
  • We talked about Electron Donating Groups (EDGs) vs. Electron Withdrawing Groups (EWGs) in Chapter 15 when talking about Diels-Alder
  • Which category would make this reaction go faster?
  • The slow step is the step where the electrons of the aromatic system attack the electrophile, so having greater electron density would make this slow step more likely to occur.
  • As such, we will call EDGs “activating” and EWGs “deactivating”
  • Halogens are weird. We’ll see why.
  • Ortho, para-directors
  • Ortho, para-directors are EDGs. Why?
  • Think again about that sigma complex. Let’s look at brominating phenol.
  • Not only does having an EDG on the positively charged carbon stabilize by induction, but when the EDG donates by resonance as well, you also get an additional resonance form.
  • A similar series of drawings can be made with para-addition
  • When you halogenate at a meta position, the positive charge is never stabilized by the substituent.
  • The majority of ortho, para-directing groups are activating as well.
  • The exception is halogens.
  • Meta-directors
  • All meta-directors are deactivating EWGs.
  • If you put an EWG at an ortho or para position, then you destabilize the sigma complex.
  • Multiple substituents
  • When possible, make everyone happy.
  • When you can’t make everyone happy, the most activating group determines the placement of the electrophile.
  • This makes sense because basically, the activating groups want this reaction to happen, and the deactivating groups don’t want it to happen.
  • The further to the right below “wins” the fight over where to put the new piece.
  • Side-chain reactions
  • Clemmenson Reduction
  • Chops off the carbonyl of ketones
  • Useful when you want to add a straight chain alkyl group.
  • First, acylate, then reduce.
  • Wolff-Kishner Reduction
  • Overall, it’s the same reaction as Clemmenson reduction, just with different reagents.
  • Benzylic Oxidation
  • If the benzyllic carbon has at least one hydrogen on it, then treatment with KMnO4or chromic acid chops the rest of the chain off and turns the first carbon into a carboxylic acid.
  • Halogenation goes faster at benzylic positions.
  • SN1/SN2 both go faster at benzylic positions.
  • Synthesis questions
  • When asked to synthesize something from benzene, the task can often seem daunting.
  • It’s important to remember that the more difficult synthesis questions of this material fall into two categories:
  • Two meta-directors ortho or para to each other
  • Step 1: Alkylate
  • Step 2: Put the other piece on
  • Step 3: Oxidize
  • Two ortho-, para-directors meta to each other
  • Step 1: Acylate
  • Step 2: Put the other piece on
  • Step 3: Reduce
  • For both of the above schemes, remember that there could be some other intervening steps.
  • Nucleophilic Aromatic Substitution
  • Addition-Elimination
  • Recognizing that you will be doing this reaction
  • There has to be a halogen on the ring.
  • Vigorous, basic conditions
  • Strong EWG’s ortho and/or para to the halogen
  • Only time where fluorine works best!
  • Because fluorine is the most electronegative, it creates a stronger partial positive at the carbon, so the nucleophilic attack is more likely to happen.
  • Overall Reaction
  • The base replaces your halogen and nothing else happens.
  • Step one: Strong nucleophile adds to the ring, generating carbanion intermediate
  • Step two: Leaving group leaves, regenerating aromaticity.
  • Elimination-Addition (Benzyne)
  • Overall reaction: Halogen leaves and strong base goes where the halogen was or one away in either direction.
  • Recognizing that this is the reaction you’re doing
  • Halogen on the ring
  • Megabase (most likely NH2-)
  • Most likely something else on the ring acting as a place-holder.
  • Step one: Base and substrate undergo E2-like reaction.
  • This really happens in two steps, not 1.
  • Step two: Base attacks benzyne intermediate and proton is picked up at other side of triple bond.
Halogen’s relationship to other substituent / Possible products
Ortho / Ortho, Meta
Meta / Ortho, Meta, Para
Para / Meta, Para
  • A weird reaction of phenols!