Electrophilic aromatic substitution (EAS) reactions – the general picture
Although the delocalized pi electrons in aromatic rings are much less reactive than those in isolated or conjugated alkenes, they can undergo electrophilic reactions given a powerful enough electrophile. Overall electrophilic addition to aromatic double bonds, however, is not generally observed – this would be energetically unfavorable because it would result in a loss of aromaticity in the product.
Instead, aromatic double bonds undergo electrophilic aromatic substitution reactions, (abbreviated EAS, sometimes called SEAr), which have an electrophilic addition step followed immediately by an electrophile elimination step. In many cases, these are preceded by the formation of the electrophile
The general mechanism usually consists of three steps:
1. Electrophile formation (various mechanisms):
2. Formation of the Wheland Intermediate (WI) (Electrophilic addition):
3. Loss of H+ of the WI to form the final product (Electrophile elimination):
Free energy reaction coordinate diagram for electrophilic substitution of benzene using a generic electrophile E+
Below is a free energy reaction coordinate diagram showing the reaction of benzene with an electrophile E+. The intermediate formed is sometimes referred to as a Wheland intermediate. Remember that this intermediate is not aromatic, even though it is somewhat stabilized by resonance, so it is much less stable than the aromatic starting material and aromatic product.
An aromatic ring is much more stable than a simple alkene. This means that if we compare an electrophilic addition step of an aromatic ring with a simple alkene, the aromatic ring starts from a much lower energy level than the alkene. This in turn means that the aromatic has a higher energy barrier to climb over than the alkene has. Even though the EAS Wheland Intermediate has some stabilization from resonance, it has still lost the aromaticity and is much less stable than the starting aromatic. The outcome is that alkenes are much more reactive towards electrophiles and electrophilic addition than are aromatics. The following diagram shows the reaction diagrams for the rate-limiting electrophilic addition step in each:
Because of this, simple aromatics only react with highly reactive electrophiles, whereas alkenes can react with less reactive ones. There are two things that can promote EAS reactions with weaker electrophiles – either a catalyst (typically a Lewis acids such as AlCl3, which activates the electrophile) or an electron-donating substituent (EDG) on the aromatic ring (which activates that ring). The reaction coordinate diagram below shows the effect of such an activating substituent on the reactivity of an aromatic ring:
In this case, the electron-withdrawing group stabilizes the Wheland intermediate and also lowers the energy of the nearby transition state. This reduces the activation energy, thereby speeding up the reaction when EDGs are present (recall Hammond’s postulate, section 5.5.) . The opposite effect can also be seen when electron-withdrawing groups are present – the EAS reaction is slowed down because the Wheland intermediate is less stable. These effects will be discussed in more detail in section 14.3.
- Klein, David R. Organic Chemistry II as a Second Language. Hoboken, NJ: John Wiley & Sons, 2006
- Parsons, A.F. Keynotes in Organic Chemistry. Oxford; Malden, MA: Blackwell Science, 2003
- Taylor, R. Electrophilic Aromatic Substitution. Chichester, West Sussex, England; New York: J. Wiley, 1990
- Label the hybridization on all the carbons in a) reacting benzene ring, b) intermediate (including resonance forms), and c) product (monosubstituted benzene ring)
- Is the energy of activation higher in the first step or second step of the mechanism? Explain your reasoning.
- If you wanted to halogenate benzene, what sort of reagent and catalyst (if needed) would you use?
- Which hydrogren is used in order to regain aromaticity after the electrophile has added to the ring?
- Critical Thinking Question: Mentioned above was the fact that electrophilic aromatic substitution can and does happen when there are substituents already present on the ring. Already present substituents will determine where something adds onto the ring in relation to itself (ortho, meta, or para position). What sort of factors do you think influence where addition will occur?
- a) All are sp2 b) Five carbons are sp2, the carbon with the attached E is sp3 hybridized c) All are sp2
- The activation energy is higher for the first step- aromatic compounds are lower in energy (“happier”) than their non-aromatic forms. Therefore it takes more energy to change a compound from being aromatic to non-aromatic, than it does in the reverse direction.
- [latex] X_2 (X=Cl, Br) + FeX_3 [/latex]
- The hydrogen used is the one attached to the same carbon that E added to
- Critical Thinking: If you came up with a) Inductive Effects (correlates to electronegativity) b) Resonance effects c) Electrostatics d) Steric Hindrance then good job! All of these influence where a substituent will add to the ring. Go to Activating and Deactivating Benzene Rings to find out more about how position is determined.
- Stevie Maxwell (UCD)
Biological example: An enzymatic electrophilic aromatic substitution reaction
The electrophile in an enzymatic EAS (SEAr) reaction is usually a carbocation. One example of an SEAr reaction can be found in the biosynthesis of vitamin K. In this reaction, an isoprenoid chain is transferred to a phenol ring as part of the and related biomolecules. In this example, carbocation intermediate B is stabilized by resonance with the electron-donating phenol oxygen.