Electrophilic Substitution in Aromatic Compounds
Electrophilic Substitution in Aromatic Compounds
Embedded Files
Electrophilic Substitution
Electrophilic Substitution
Electrophilic substitution in aromatic systems is a fundamental type of reaction in organic chemistry, particularly significant for the chemistry of benzene and other aromatic compounds. This reaction mechanism allows aromatic compounds to retain their characteristic stability while introducing various functional groups into the aromatic ring.
Aromatic compounds, such as benzene, possess a special type of stability due to their delocalized π-electron system. This delocalization over the cyclic structure contributes to their reluctance to undergo reactions that would disrupt this aromatic electron system, such as addition reactions. Instead, aromatic compounds favour electrophilic substitution reactions, which preserve the integrity of the aromatic ring.
General Patterns in the Mechanism
General Patterns in the Mechanism
The mechanisms in electrophilic substitution normally follow two main steps:
1. Formation of a Sigma complex (sometimes called the arenium ion).
1. Formation of a Sigma complex (sometimes called the arenium ion).
The electrophile attacks the π-electron-rich aromatic ring, temporarily disrupting the delocalization to form a high-energy intermediate known as an arenium ion or sigma complex. This intermediate has a positive charge, usually delocalized over several positions of the ring.
2. Deprotonation (removal of a hydrogen) to regain its aromatic structure back.
2. Deprotonation (removal of a hydrogen) to regain its aromatic structure back.
However, the next step, loss of the proton at the sp3 hybridized carbon, regenerates the aromatic ring. This process is more favoured than nucleophilic trapping by the anion that accompanies E +. One must note that the anion may also deprotonate the sigma complex (see example of nitration)
Even though electrophilic substitution reactions follow this pattern, each mechanism may have its own extra steps in generating the electrophile.
The mechanism above is showing the electrophilic substitution of benzene with an electrophile E. Notice how there are two major steps in the mechanism.
In the first step, electrophile E attacks the delocalised pi electrons on the benzene ring to form a sigma complex. The sigma complex is not aromatic as the delocalised ring of electrons are disrupted.
In the second step, the C-H bond breaks to regenerate the aromatic system in the ring.
Extra note: In reality, the sigma complex undergoes the following changes (shown in black below) so that the electrons in the C-H bond regenerate the aromatic system. We draw a simplified version (a sort of 3 in 1 version).
Nitration
Nitration
The nitration of benzene is a classic example of an electrophilic aromatic substitution reaction, where a nitro group (-NO2) is introduced into the benzene ring. This reaction is typically carried out using a mixture of concentrated nitric acid (HNO3) and concentrated sulfuric acid (H2SO4), which act together to generate the electrophile.
Step 1: Generating the nitronium ion
Step 1: Generating the nitronium ion
The first step involves the generation of the nitronium ion (NO2 +) the active electrophile in the reaction. This occurs when nitric acid reacts with sulfuric acid. Sulfuric acid protonates nitric acid, producing water and the nitronium ion.
Step 2: Formation of the sigma complex
Step 2: Formation of the sigma complex
The nitronium ion, being a strong electrophile, attacks the π-electron-rich benzene ring. This attack leads to the formation of a sigma complex (also known as an arenium ion), where the delocalization of π electrons is temporarily disrupted. One of the sp² hybridized carbon atoms in the benzene ring forms a new sigma bond with the nitronium ion, while the π electrons are used to stabilize the positive charge developed on the ring. This positive charge is delocalized over three carbon atoms, including the one bonded to the nitronium ion, reducing the energy of the intermediate.
Step 3: Deprotonation to regain its aromatic structure back
Step 3: Deprotonation to regain its aromatic structure back
In the final step, a base (usually the bisulfate anion, HSO4-, from the sulfuric acid) removes a proton (H+ ) from the sigma complex. This step restores the aromaticity of the benzene ring by re-establishing the delocalized π-electron system. The molecule of nitrobenzene is formed, and the aromatic stability of the ring is regained.
This process illustrates the typical mechanism of electrophilic aromatic substitution, where the high electron density of the aromatic ring facilitates the initial attack by an electrophile, followed by steps that restore the aromatic system, allowing the introduction of various functional groups while maintaining the aromatic stability of the ring.
Sulfonation
Sulfonation
The sulfonation of benzene is another prime example of an electrophilic aromatic substitution reaction, where a sulfonic acid group (-SO3H) is introduced to the benzene ring. This reaction typically employs sulfur trioxide (SO3 ) or concentrated sulfuric acid (H2SO4) as the sulfonating agent. Here's the mechanism broken down into its fundamental steps:
The electrophile in sulfonation is sulfur trioxide. Concentrated sulfuric acid does not sulfonate benzene at room temperature. However, a more reactive form, called fuming sulfuric acid, permits electrophilic attack by SO3. Commercial fuming sulfuric acid is made by adding about 8% of sulfur trioxide, SO3, to the concentrated acid. Because of the strong electron-withdrawing effect of the three oxygens, the sulfur in SO3 is electrophilic enough to attack benzene directly.
Step 1: Formation of the sigma complex
Step 1: Formation of the sigma complex
The SO3 molecule, acting as the electrophile, attacks the electron-rich aromatic ring of benzene, leading to the formation of a sigma complex. This intermediate is characterized by the addition of the sulfonic acid group to one of the carbon atoms of the ring, with a resultant positive charge being delocalized across the ring structure. This delocalization reduces the energy penalty associated with the formation of the positively charged intermediate.
Step 2: Deprotonation and Restoration of Aromaticity
Step 2: Deprotonation and Restoration of Aromaticity
The final step involves the removal of a proton from the sigma complex by the base present in the reaction mixture, typically the bisulfate anion HSO4+ generated in situ. The loss of this proton allows the electrons to reorganize into a delocalized π system, restoring the aromatic stability of the benzene ring and finalizing the attachment of the sulfonic acid group
Sulfonation is reversible
Sulfonation is reversible
The sulfonation of benzene to form benzenesulfonic acid illustrates a critical mechanism where the electrophile is a sulfur-containing species. Unlike many other electrophilic aromatic substitution reactions, sulfonation is unique because it is reversible. The reaction can be driven backward by heating the sulfonated product with dilute sulfuric acid, which helps to remove the sulfonic acid group and regenerate the original benzene ring. This reversibility makes sulfonation a valuable tool for protecting the benzene ring during complex synthetic sequences, allowing for temporary modification of the ring's chemical reactivity. The chemical reaction for reversing sulfonation can be found below.
The reversibility of sulfonation may also be used to control further aromatic substitution processes. The ring carbon containing the substituent is blocked from attack, and electrophiles are directed to other positions. Thus, the sulfonic acid group can be introduced to serve as a directing blocking group and then removed by reverse sulfonation.
Sulfonation plays a crucial role in the production of detergents, dyes, and sulfa drugs, showcasing its industrial and pharmaceutical significance.
Halogenation
Halogenation
The halogenation of benzene is a key electrophilic aromatic substitution reaction where a halogen atom replaces a hydrogen atom on the benzene ring, resulting in the formation of an aryl halide. This reaction typically involves the use of a halogen, where X can be chlorine, Cl2), or bromine, Br2), and a Lewis acid catalyst such as iron (III) chloride FeCl3) for chlorination or iron (III) bromide (FeBr3) for bromination. Here's how the mechanism unfolds.
Step 1: Generation of the Electrophile
Step 1: Generation of the Electrophile
The first step is the formation of the electrophilic species. The diatomic halogen molecule reacts with the Lewis acid catalyst, facilitating the dissociation of the halogen into a positively charged halogen ion and a complex anion. The halide ion acts as the electrophile. This electrophile is highly reactive towards the π-electron-rich aromatic ring of benzene.
Step 2: Formation of the Sigma Complex
Step 2: Formation of the Sigma Complex
The electrophilic halogen ion attacks the benzene ring, leading to the formation of a sigma complex, also known as an arenium ion. This intermediate disrupts the aromaticity by adding the halogen to one of the carbon atoms, creating a positive charge that is delocalized over the adjacent carbon atoms. The delocalization helps to stabilize this high-energy intermediate.
Step 3: Deprotonation and Restoration of Aromaticity
Step 3: Deprotonation and Restoration of Aromaticity
In the final step, a base, often the complex anion formed in the first step (FeX4- ), removes a proton from the sigma complex to form HX and regenerate the Friedel-Crafts catalyst (FeX4). This restores the delocalized π-electron system, bringing back the aromatic character of the ring with the halogen now attached.
Does Halogenation work with fluorine and iodine?
Does Halogenation work with fluorine and iodine?
The halogenation reaction is most commonly performed with chlorine and bromine because fluorine is too reactive (often reacting explosively with benzene) and iodine is typically not reactive enough without additional activation. The Lewis acid catalyst is crucial for increasing the reactivity of the halogen molecule, making the halogenation of benzene feasible under relatively mild conditions.
Alkylation
Alkylation
None of the electrophilic substitutions mentioned so far has led to carbon – carbon bond formation, one of the primary challenges in organic chemistry. In principle, such reactions could be carried out with benzene in the presence of a sufficiently electrophilic carbon-based electrophile. The secret to the success is the use of a Lewis acid, usually aluminum chloride.
The alkylation of benzene is a key electrophilic aromatic substitution reaction where an alkyl group is introduced to the benzene ring, typically using an alkyl halide (R-X) in the presence of a Lewis acid catalyst like aluminum chloride (AlCl3). This reaction, known as the Friedel-Crafts alkylation, is crucial for synthesizing various alkylated benzene derivatives.
Step 1: Generation of the Electrophile
Step 1: Generation of the Electrophile
The first step involves the formation of a more reactive electrophile from the alkyl halide. The Lewis acid catalyst AlCl3, due to its strong electron-accepting nature, reacts with the alkyl halide, facilitating the departure of the halide ion and forming a highly reactive carbocation R+ or an R-AlCl3 complex, which acts as the electrophile.
Step 2: Formation of the Sigma Complex
Step 2: Formation of the Sigma Complex
The generated electrophile (R+ ) attacks the π-electron-rich benzene ring, temporarily disrupting the delocalization to form a sigma complex (also known as an arenium ion). This intermediate features a positive charge that is delocalized over the adjacent carbon atoms of the ring, stabilizing the complex somewhat despite the high energy associated with the positive charge.
Step 3: Deprotonation and Restoration of Aromaticity
Step 3: Deprotonation and Restoration of Aromaticity
A base present in the reaction mixture, often the Friedel-Crafts catalyst ion (AlX3+ ) produced in the first step, removes a proton from the sigma complex. This step restores the delocalized π-electron system, regenerating the aromatic stability of the benzene ring and completing the attachment of the alkyl group
Uses of Friedel-Crafts alkylation
Uses of Friedel-Crafts alkylation
The Friedel-Crafts alkylation enables the synthesis of alkylbenzenes from simple benzene and alkyl halides, significantly broadening the scope of compounds accessible through aromatic chemistry. This reaction is particularly useful for adding straight-chain or branched alkyl groups to the benzene ring.
Considerations and Limitations
Considerations and Limitations
Rearrangement: One notable aspect of Friedel-Crafts alkylation is the potential for carbocation rearrangement. The initially formed carbocation may undergo hydride or alkyl shifts to form a more stable carbocation, leading to rearranged products.
Polyalkylation: Since the alkylated benzene product is more reactive than the starting benzene, over-alkylation can occur. Excess reactants or careful control of reaction conditions are required to minimize this effect.
Alkanoylation
Alkanoylation
The acylation (also known as alkanoylation) of benzene is a critical electrophilic aromatic substitution reaction that introduces an acyl group (RCO) onto the benzene ring, typically using an acid chloride (RCOCl) in the presence of a Lewis acid catalyst, such as aluminum chloride (AlCl3). This reaction is known as the Friedel-Crafts acylation and is instrumental in synthesizing ketones with aromatic rings. Here's a breakdown of the mechanism. Acylation proceeds through the acylium cations. This section describes how these ions readily attack benzene to form ketones.
Step 1: Generation of the Electrophile
Step 1: Generation of the Electrophile
The process begins with the formation of the acylium ion (RCO+ ), the active electrophile, from the acid chloride. The Lewis acid catalyst (AlCl3) interacts with the acid chloride, facilitating the removal of the chloride ion (Cl- ) and creating the highly reactive acylium ion:
The acylium ion is stabilized by resonance, which distributes the positive charge over the carbonyl group, making it less prone to rearrangement compared to carbocations in alkylations.
Step 2: Formation of the Sigma Complex
Step 2: Formation of the Sigma Complex
The acylium ion then attacks the π-electron-rich benzene ring, forming a sigma complex. This intermediate disrupts the aromaticity of the benzene ring by adding the acyl group to one of the carbon atoms, resulting in a positive charge that is delocalized over the adjacent carbon atoms. This delocalization partially stabilizes the positive charge.
Step 3: Deprotonation and Restoration of Aromaticity
Step 3: Deprotonation and Restoration of Aromaticity
Finally, a base in the reaction mixture, often the complex anion (AlCl4- ), removes a proton from the sigma complex. This action restores the delocalized π-electron system of the benzene ring, returning it to its aromatic state with the newly attached acyl group in place.
Considerations and Advantages
Considerations and Advantages
The Friedel-Crafts acylation offers a powerful method for introducing carbonyl functionalities into aromatic compounds, yielding aromatic ketones.
Unlike alkylation, acylation does not lead to carbocation rearrangement, thanks to the stability of the acylium ion. This results in more predictable products. The acyl group can be further transformed into other functional groups through subsequent reactions, providing a versatile route to a wide range of derivatives. The product of acylation, an aromatic ketone, is generally less reactive than the starting benzene due to the electron-withdrawing effect of the carbonyl group. This characteristic reduces the likelihood of polyacylation under controlled conditions.
The Reagents and Conditions for each electrophilic substitution
The Reagents and Conditions for each electrophilic substitution
The reaction conditions for various electrophilic aromatic substitution reactions like nitration, sulfonation, halogenation, alkylation, and acylation are specific to each type of reaction. Here's a brief overview:
Page updated
Google Sites
Report abuse