Question

In the Gatterman-Koch reaction, a formyl group (-CHO) is introduced directly onto a benzene ring. For example, reaction of toluene with CO and \(\mathrm{HCl}\) in the presence of mixed \(\mathrm{CuCl} / \mathrm{AlCl}_{3}\) gives \(p\) -methylbenzaldehyde. Propose a mechanism.

Short answer

The Gatterman-Koch reaction forms p-methylbenzaldehyde from toluene via an electrophilic aromatic substitution of an acylium ion.

Step-by-step solution

Formation of Vilsmeier Reagent

In the Gatterman-Koch reaction, the first step involves the formation of a Vilsmeier-type complex. This is achieved by the reaction of carbon monoxide (CO) with hydrogen chloride (HCl) in the presence of catalytic amounts of copper(I) chloride (CuCl). This forms a chloroformyl cation ( ext{Cl}- ext{C}^+= ext{O}).

Formation of the Electrophile

The chloroformyl cation, acting as a strong electrophile, is then stabilized and further activated by a complex with aluminum chloride ( ext{AlCl}_3), resulting in a positively charged acylium ion ( ext{[O=C]^+=AlCl3^-}).

Electrophilic Aromatic Substitution

The acylium ion reacts with the electron-rich aromatic ring of toluene. Toluene's methyl group is an activating group, directing the incoming electrophile to the ortho and para positions. Due to sterics and kinetics, para substitution is often more favorable, resulting in the formation of p-methylbenzaldehyde.

Rearomatization

After the electrophilic aromatic substitution, the intermediate cation loses a proton ( ext{H}^+) to restore aromaticity to the benzene ring. This step is typically facilitated by a base present in the reaction medium.

Regeneration of the Catalyst

Finally, the catalytic complex used in the reaction ( ext{CuCl} / ext{AlCl}_3) is regenerated, allowing the reaction to proceed cyclically with the introduction of new substrates.

Key concepts

Vilsmeier Reagent

The Vilsmeier reagent is a critical component in the Gatterman-Koch reaction, which is utilized for formylation of aromatic rings.
This reagent is typically formed from a reaction involving carbon monoxide (CO) and hydrogen chloride (HCl), in the presence of copper(I) chloride (CuCl) as a catalyst.
It creates a chloroformyl cation (\[\text{Cl-C}^+=\text{O}\]), a potent electrophile essential for further reaction steps.
The role of the Vilsmeier reagent in this process is pivotal, as it combines specific components that can proceed to interact effectively with the aromatic system.
Without this initial step, subsequent transformations toward the formation of acylium ions and the desired aromatic substitution would not be feasible.

• This complex exhibits high reactivity due to its positive carbon center, making it indispensable in aromatic substitutions where electron-rich systems are targeted.
• Furthermore, the catalyst (CuCl) assists this generation by stabilizing the formation of the chloroformyl cation.

Electrophilic Aromatic Substitution

Electrophilic aromatic substitution (EAS) is a mechanism whereby an aromatic compound undergoes substitution, maintaining its aromaticity.
In the context of the Gatterman-Koch reaction, the key electrophile is the acylium ion formed by subsequent activation of the Vilsmeier reagent formed initially.
This mechanism involves several crucial steps:

• The aromatic ring, being electron-rich, encounters the acylium ion, which is a strong electrophile due to its positively charged carbon.
• Through the attack of pi electrons, a sigma complex, or arenium ion, forms, temporarily disrupting the aromatic system.
• To restore aromaticity, a hydrogen ion is expelled. Often, this step is facilitated by a base which accepts the proton efficiently.

The preference for substitution on either the ortho or para position is guided by the presence of electron-donating groups. In toluene, a methyl group directs the substitution to the para position due to sterics, favoring reaction stability.

Acylium Ion

The acylium ion is crucial in many electrophilic aromatic substitution reactions, including the Gatterman-Koch reaction.
This ion, (\[\text{[O=C]^+=AlCl_3^-}\]), is generated from the Vilsmeier reagent's activated intermediate.
It presents itself as a powerful electrophile, with a linear structure that contributes to its stability and reactivity within aromatic chemistry.

• The formation involves the interaction of AlClthe catalyst, with the chloroformyl cation, which enhances the electrophilic character significantly.
• Upon formation, it actively seeks electron-rich environments, making aromatics such as benzene ideal substrates as they contain delocalized pi-electron clouds.

Through its influence, it facilitates the conversion of an ordinary aromatic into a formyl-substituted product, contributing to the gram-scale synthetic routes for aldehydes.