Summary of electrophilic aromatic substitution reactions
- 1. Mechanism: A nucleophilic aromatic ring attacks the electrophile E+, giving a cation, and loses H+ to regain its aromaticity. This substitutes C-H for C-E.
- 2. Key reactions: Bromination, chlorination, Friedel-Crafts alkylation (R) & acylation (C(O)R). nitration (NO2), sulfonation (SO3H). Most reactions utilize acid or Lewis acids to create reactive electrophiles.
- 3. Substituents – Activation: Electron-donating groups at a ring increase nucleophilicity and reactivity. Electron-withdrawing groups work the opposite.
- 4. Substituent – Regioselectivity: Activators lead to ortho and para products. Deactivating groups direct meta (excl. halogens).
- 5. Examples: TNT synthesis nicely exemplifies ring activation. Pharmaceuticals use electrophilic aromatic substitution – sometimes with heterocycles!
- 6. Orbitals: Addition is fastest where overlap of donor (HOMO) and acceptor (LUMO) is best. However, orbital models do not explain the full story!
- Common mistakes and reaction examples at the end!
1. mechanism of electrophilic aromatic substitution
So what is electrophilic aromatic substitution?
Substitution as it replaces a C-H bond at an aromatic ring with a new C-E bond.
Electrophilic because our new E group was introduced as an electrophile.
Due to its aromaticity, benzene is relatively unreactive. Unlike alkenes, strong electrophiles give substitution products and not addition products.
Because our new group is an electrophile, the double bond of the aromatic ring has to be the nucleophile (just like in electrophilic additions)! Here’s how to identify nucleophiles vs electrophiles.
Note that the electrophile can be a neutral molecule that’s positively polarized, it does not have to be positively charged.

Note: The order is ‘form C-E, then break C-H’. While the other way around can work, it requires different reaction conditions (very strong base to deprotonate C-H) and is not as broadly applicable.
Let’s see what we can learn from this energy diagram.
1. One of the double bonds attacks the electrophile (here: NO2+). Because this breaks the aromaticity of the starting material, the step requires quite a bit of activation energy (the molecule has to have energy to climb the hill of TS1).

2. The addition product is a carbocation (the double bond was ‘invested’ by one carbon to form the bond with E+, the other carbon has one electron less in its proximity and is now a non-aromatic carbocation). The positive charge sits next to the other double bonds , so it is somewhat stabilized and delocalized. This is a real intermediate whereas the transition states are just “snapshots at maximum energy”. This is also called Wheland intermediate or sigma complex.
3. The deprotonation occurs quite easily (the hill to TS2 is lower than the first one) and gives the stable substituted aromatic product. By the way, you don’t need to add base (e.g., KOH) for this step; the proton will get lost to other molecules present in the reaction or solvent. If the final product is lower in energy vs. starting material (more specifically, “enthalpy”), the reaction is exothermic.
But benzene is very simple and boring. In sections 2-4, we cover:
2. What types of electrophiles we can add and how we generate them
3. How other ring substituents can accelerate or slow down this reaction (activation)
4. How other ring substituents influence where the reaction occurs (regioselecitvity)
By the way, this is an old reaction! Pioneering work came from the Brit Armstrong in the 1880s already, and the American George Wheland in the 20th century.

Source: J. Chem. Soc., Trans., 1887, 51, 258

From our videos, we know that the early days of chemistry were was a bit crazy. Even simple benzene was disputed (left: Armstrong’s “centroid formula”). We can’t blame these OG chemists as our modern knowledge evolved out of the many dubious theories.
2. Key electrophilic aromatic substitution reactions
1. Bromination or chlorination: Uses molecular bromine or chlorine to form a C-Br or C-Cl bond, needs Lewis acid
2. Friedel Crafts alkylation & acylation: Forms a C-C bond, needs Lewis acid
3. Nitration: Incorporation of a nitro group (-NO2), needs acid
4. Sulfonation: Incorporation of a sulfonic acid (-SO3H), needs acid
These reactions have the same fundamental mechanism… but they differ in how they generate their reactive electrophile. They all use some sort of reagent (green/purple boxes) to get to the true electrophilic species that is attacked by the aromatic ring.

Bromination, chlorination and Friedel-Crafts reactions use a Lewis acid (=electrophilic metal compounds that things with electron pairs can coordinate to). This makes the Br, Cl, R or C(O)R centers more positively polarized, so they are more reactive with the double bond.
Nitration and sulfonation use a ‘normal’ acid (e.g., sulfuric acid) to protonate the reactants and activate them into more electrophilic species. Nitration is a particularly useful reaction as the group can converted to amino or hydroxyl groups.
After initial electrophile generation, all reactions follow the same steps and experience the same substituent effects (Sections 3. and 4. below). For full clarity, I might explain the nuances of each reaction in more detail in future posts.
There are two important points I want to point out on the halogenation reactions above: bromination and chlorination.
1) The typical conditions are bromine or chlorine + Lewis acid, but students will see in more advanced classes that there are other sources of electrophilic bromine or chlorine, like NBS or NCS (N-bromo/chloro-succinimide). I’ll probably explain these reagents more in separate posts.
In organic chemistry, there are always multiple ways of achieving a certain reaction or generating a certain reactive species, e.g., an electrophile.
2) Chemistry class syllabus usually ignores the other two cousins in the halogen family: iodine and fluorine. But that doesn’t mean that they cannot participate in these reactions! The point is more that these reactions are less common and straightforward, so they are usually not discussed.
If you can somehow generate activated/ polarized electrophiles (I+ or F+), they will also react with electron-rich aromatic rings just like Cl+ or Br+ shown above. While there are several options for iodination (using I2 and additional reactants like acids), fluorination is more challenging and requires special reagents (not F2). Aryl fluorides are thus usually made with nucleophilic aromatic substitution reactions like the Balz-Schiemann reaction.
3. Activating and deactivating groups
Recall: Our aromatic ring is a nucleophile, attracted to positive charge or polarization (which are electrophiles) because it has a decent amount of electron density.
The higher the electron-density in a ring, the more nucleophilic and more reactive it will be. This accelerates aromatic electrophilic substitution (higher reaction rate).
The electron-density of aromatic systems is influenced by the ring substituents. For example, nitrobenzene does not undergo normal Friedel-Crafts acylations.
Activating groups are electron-donating groups that increase nucleophilicity and reactivity of an aromatic ring, usually through mesomeric π effects (resonance).
Deactivating groups are electron-withdrawing groups that decrease nucleophilicity and reactivity either via inductive σ or mesomeric π effects.
Here are the key groups, (directional) strength and primary drivers.
Activators tend to be π donors (they push/ delocalize their electron pair into the ring) while deactivators tend to be π acceptors (they accept delocalized electrons, acting as an electron sink). If this doesn’t make sense, please read up on resonance.

Note the key counterintuitive example: halogens deactivate rings more strongly (due to their negative inductive σ effect, think high electronegativity) than they activate them (due to their mesomeric π effect, they have a free electron pair).
Another way to think about these groups is to revisit our energy diagram. The TS1 is partially positively charged and the intermediate is fully positively charged. Obviously, this positive charge will be very comfortable if there is a lot of electron density in the ring (charges like to be spread across and stabilized across atoms). Inversely, deactivators would make the intermediate unhappy. It’s like robbing someone who’s already very poor – not the best look.

The stabilizing effects for activating groups mean that TS1 requires a lower activation energy (because the ring is more nucleophilic) and our carbocation intermediate is also lower in energy (the charge is better stabilized by the electron-rich ring).
Note: It’s critical that these groups are directly attached. If there is an “alkyl spacer” between the ring and a strong (de)activator, the effect will vanish. The donor or acceptor groups need to be conjugated with the ring! The substituents here would be more like σ donors.

4. Regioselectivity of aromatic electrophilic substitutions (Directing Effects)
All activating groups and halogens direct/favor substitution at ortho & para positions.
All deactivating groups excluding halogens direct/favor substitution at meta.
This regioselectivity can be rationalized by looking at the delocalization/ stabilization of the carbocation intermediate. Ortho and para additions favor carbocations where the positive charge sits next to the R group (either directly in case of ortho or after delocalization in the case of para).
If R can stabilize this positive charge as a σ or π electron donor, it will lower the energy of the carbocation and prefer these pathways over the meta addition.

Well if R is an electron-withdrawing group, the positive charge will absolutely hate being next to it (electron-sink next to something that already doesn’t have enough electrons). Thus, deactivating groups avoid ortho and para substitution and show meta selectivity.
Halogens are again sneaky. Regarding ring activation, their negative inductive effect (electron-withdrawal) overrides their positive mesomeric effect (electron pair donation). Regarding regioselectivity, the mesomeric effect is more important (deal with it). Outside of this special case, all groups follow the same rules.
5. Examples: Tnt & pHARMACEUTICALS
Our first example is 2,4,6-trinitrotoluene or TNT. One of many ways of synthesizing TNT is exactly what you think: take toluene and nitrate the heck out of it.
The issue? Substituent effects!
You see, while toluene is decently nucleophilic (it’s slightly activated through the methyl group), it becomes less and less reactive the more nitro groups are attached.

The first addition gives a mix of ortho and para substituted products. final nitration only occurs at high temperatures and use of fuming sulfuric acid, a particularly reactive form of sulfuric acid containing additional sulfur trioxide. There are easier and more clever ways to make TNT, but that shouldn’t be our focus.
You also see that just because TNT is deactivated towards electrophilic aromatic substitution, it still likes to explode violently. Reactivity is always relative. This is because detonation does not depend on the nucleophilicity of the aromatic ring 🙂
All reactions can happen either between two molecules (intermolecularly) or also within a single molecule (intramolecularly), if it has all the needed functional groups.
Most pharmaceuticals contain aromatic rings so we can find these reactions in their syntheses. One example is the drug lifitegrast. Its synthesis uses an intramolecular Friedel-Crafts alkylation to create the bicyclic core.

Final lesson: Heterocycles can also be nucleophiles! (aromatic ring with heteroatom)
The synthesis of the antibiotic metronidazole is very simple. The first step is nitration of the ring with carbon as the nucleophile. In the second step, the nitrogen acts as the nucleophile and undergoes a SN2 reaction with the alkyl chloride.

The five-membered rings pyrrole (heteroatom: N) and furan (heteroatom: O) are very electron-rich so we also often see them engage in electrophilic substitution reactions.

This is because the electron pair can stabilize the positive charge during the reaction mechanism. It’s like having an activating substituent effect within the ring!
6. Orbitals in aromatic substitutions
You probably shouldn’t read this section if you’re just learning about aromatic substitutions.
Drawing resonance structures is useful for us mortal humans. However, they are just tools and don’t correspond to reality. After all, we’re taught that “real structure” of a molecule is a mix of all “good” resonance structures. Advanced readers might ask themselves if orbitals can be useful predictors for aromatic reactions?
We won’t go through orbital theory here, but in short: When atoms form bonds in a molecule, their atomic orbitals combine to molecular orbitals. These can be filled with electrons or empty (or half-empty, if it’s a radical). The highest-energy filled orbital (HOMO, occupied) influences nucleophilic behavior and the lowest-energy empty orbital (LUMO, unoccupied) influences electrophilic behavior.
Looking at orbitals can be partially insightful. Here’s a 3D visualization of the early days of an electrophilic aromatic nitration. The HOMO of chlorobenzene (nucleophile) is getting close to the LUMO of the nitronium cation (electrophile). How will they add?
Electrophilic attack will occur where p orbitals contribute most to the π HOMO. The higher the overlap of donor (HOMO) and acceptor (LUMO), the faster the reaction.
You can see that on the ring, para and (to a slightly lesser degree) ortho positions have high contributions, while there is “almost no orbital” on meta. Any electrophilic attack at meta would thus be disfavored (low orbital overlap).
Our nitronium electrophile has a slightly higher LUMO localization at the central nitrogen, meaning the nitrogen is more electrophilic than the oxygens!
So, it looks like molecular orbitals can nicely predict the regioselectivity that we observe for chlorobenzene. So why don’t people talk about orbitals in the same fashion as they do e.g., for the Diels-Alder reaction?
- Aromatic substitutions are one of the first reactions students, so going into orbitals would be an overkill that makes everyone hate chemistry even more.
- More importantly, they don’t always give the full picture. Consider the HOMO of nitrobenzene below. This aromatic ring is deactivated and should attack meta.
We do see that the para position is not contributing to the HOMO at all, but the orbital structure does not tell us why there is no substitution at ortho! In this case, our resonance structure analysis is actually more helpful because it tells us that the ortho-position of nitro groups is particularly electron-poor.
There are other ways to analyse this, e.g., by computing charge density. Below you can find an atomic charge analysis for benzene, aniline and nitrobenzene. Ignore the method or units – simply put, a more negative number equals more electron-density at a given atom. More electron-density means more nucleophilic and more reactive towards electrophiles.
Question to you: What are important takeaways from this charge analysis?

Source: Phys. Chem. Chem. Phys., 2016, 18, 11624
Here are some thoughts:
- Benzene: Obviously, hydrogens are more electropositive than carbons (they have a positive charge number). The molecule is symmetrical.
- Aniline: Electron-density is higher at ortho and para relative to meta, explaining the directing effect. Relative to benzene, ortho and para have higher electron density, i.e., the aniline ring is more activated and reactive .
Note that there is a lot of electron density on the amine as well! (Aniline can also react as a N-nucleophile! See common mistakes) - Nitrobenzene: Electron-density is highest at meta relative to ortho and para, explaining the directing effect. Now, the carbons all have lower electron density, in line with deactivation / lowering of reactivity due to the nitro group.
Sidenote: The nitro group’s electron-withdrawing effect further polarizes the C-H hydrogens as they are more electron-poor in nitrobenzene.
So, orbital theory is sometimes more, and sometimes less useful. Generally, combining multiple models and perspectives gives us a better appreciation. For now, you can happily ignore orbitals for these reactions (but not for others!).
Common Mistakes in Electrophilic Aromatic Substitutions
Students can feel overwhelmed trying to remember effects or specific aromatic substitutions. This can lead to common mistakes or errors, including:
Mixing up ortho, para and meta: This is the first hurdle for new students. If you’re struggling with this, try remembering it this way: Meta is in the middle between the other two. The letter o comes before p in the alphabet, so ortho is closer to R.
Thinking too superficially: Although electrophilic substitution is the most common reaction of aromatic compounds you’ll see, don’t jump to conclusions too quickly. In this example, an acyl chloride (electrophile) would lead to O-acylation instead of electrophilic aromatic substitution. The benzene ring is deactivated and thus not nucleophilic enough.

Along the same lines: In section 6. Orbitals, we saw that charge analysis suggests high electron density at the nitrogen of aniline. Again, under many conditions, anilines can react as N nucleophiles instead of C nucleophiles (e.g., alkylation at nitrogen instead of at carbon).
Electrophilic or nucleophilic?: Get your terms right. Nucleophilic aromatic substitution reaction does not substitute C-H but rather C-X, where X is a good leaving group. This is the opposite of what saw for the electrophilic substitution: our aromatic ring is the electrophile here. This reaction is explained here.
Misunderstanding substituent effects: Abbreviations can be confusing, and we might wrongly believe a specific atom or an abbreviated group to be activating or deactivating. Before you go with it, double-check why a substituent would be an electron-donating group or an electron-withdrawing group. E.g., can you really find an electron-pair that is driving a positive mesomeric effect?
Remember to consider if a newly introduced functional group is more or less activating. Reactions often use an excess of reagents (more moles of reagent than starting material). Adding one activating group? The ring might add more (e.g., polyalkylation in Friedel-Crafts alkylations). Want to add more than one deactivating group? This might be challenging (remember our TNT example)!
Electrophilic Aromatic Substitution Examples

Here are additional questions to test your knowledge of the reaction mechanism and directing effects of substituents.
The first exercise is pretty straight-forward, with the fluoro-substituted ring being less activated (thus, bromination occurs on the other one, para to the aryl-aryl bond).
The same idea applies to the question on the right, where we expect the inductive acceptor effect of the trifluoromethyl group to deactivate the ring towards sulfonation.
The Friedel-Crafts acylation is pretty obvious (para to the electron-donating ether group).
Last, we have a Friedel-Crafts like C-C bond formation. Instead of a alkyl halide and Lewis acid, we generate our carbon electrophile by protonation of the double bond with sulfuric acid.

Hope this summary helped you get a good overview of this class of aromatic reactions.
Feel free to check out my other posts and videos for more content.