Friedel–Crafts Alkylation and Acylation

Introduction

Charles Freidel and James Crafts invented the Friedel–Crafts reactions in 1877 to attach substituents to aromatic rings. The alkylation and acylation responses are the two most common Friedel–Crafts responses. Friedel–Crafts Alkylation refers to the substitution of an alkyl grouping for an aromatic proton. With the assistance of a carbocation, an electrophilic attack on the aromatic ring is completed. The Friedel Crafts alkylation reaction is a response that involves alkyl halides as reactants to create alkylbenzenes.

Mechanism of Friedel–Crafts Alkylation 

The Friedel–Crafts alkylation involves reacting alkyl halides or alkenes with aromatic hydrocarbons to produce alkylated products like alkylbenzenes. A hydrogen atom on the aromatic ring is removed and replaced with an electrophile in this process. It arises due to electrophilic aromatic substitution, which is accelerated by strong Lewis acids like AlCl3 or FeCl3. Depending on the amount of substituents on the aromatic ring, the positively charged alkyl species interact with it as a simple carbocation or a Lewis acid carbocation complex alkyl halide (i.e., primary, secondary, or tertiary alkyl halide). The mechanism of Friedel–Crafts alkylation is a multi-step process. To generate the carbocation, the alkyl halide and Lewis acid react first. The carbocation then attacks the aromatic ring, breaking one of the ring’s double bonds and forming a non-aromatic intermediate in the process. This intermediate is deprotonated, the ring regains aromaticity, and the proton removed produces an acid, restoring the Lewis acid catalyst. The acylation reaction mechanism for tertiary alkyl halides is depicted in the diagram below. 

A carbocation-like complex with the Lewis acid, [R(+)—-(X—-MXn)(–)], is more likely to be associated with primary (and potentially secondary) alkyl halides than a free carbocation. Because alkyl groups are activators for the Friedel–Crafts reaction, this reaction has the drawback that the result is more nucleophilic than the reactant. As a result, overalkylation may occur. As in the t-butylation of 1,4-dimethoxybenzene, steric hindrance can be used to limit the amount of alkylations.

Furthermore, the reaction is only helpful for primary alkyl halides when a 5- or 6-membered ring is produced intramolecularly. The reaction is confined to tertiary alkylating agents, some secondary alkylating agents (carbocation rearrangement is degenerate), or alkylating agents that provide stable carbocations in the intermolecular instance (e.g., benzylic or allylic ones). The carbocation-like complex (R(+)—-X—-Al(-)Cl3) will go through a carbocation adjustment reaction in the case of primary alkyl halides, yielding nearly exclusively the rearranged product obtained from a secondary or tertiary carbocation.

Alkylation isn’t just for alkyl halides; any carbocationic intermediate, such as those generated from alkenes and a protic acid, Lewis acid, enones, and epoxides, can be used in Friedel–Crafts processes. 

One example is the production of neopentyl from benzene and 3-chloride-2-methylpropene.

 H2C=C(CH3)CH2Cl + C6H6 → C6H5C(CH3)2CH2Cl

Mechanism of Friedel–Crafts Acylation

Friedel–Crafts alkylation is another name for it. The acylation of aromatic rings is known as Friedel–Crafts acylation. Acyl chlorides are common acylating agents. Acids and aluminium trichloride are common Lewis acid catalysts. However, unlike the Friedel–Crafts alkylation, where the catalyst is constantly regenerated because the resulting ketone forms a somewhat persistent complex with Lewis acids such as AlCl3, a stoichiometric amount or more of the “catalyst” must be used in most cases. Acid anhydrides can also be used for Friedel–Crafts acylation. Friedel–Crafts alkylation has comparable reaction conditions. Compared to the alkylation reaction, this reaction has various advantages. The ketone result is usually less reactive than the original molecule due to the electron-withdrawing effect of the carbonyl group. Hence repeated acylations do not occur. Also, because the acylium ion is stabilised by a resonance structure with a positive charge on the oxygen, there are no carbocation rearrangements.

The stability of the acyl chloride reagent determines the viability of the Friedel–Crafts acylation. Isolating formyl chloride, for example, is impossible. As a result, formyl chloride must be generated in situ to produce benzaldehyde via the Friedel–Crafts pathway. This is performed using the Gattermann-Koch reaction, catalysed by a combination of aluminium chloride and cuprous chloride, and involves treating benzene with carbon monoxide and hydrogen chloride under high force.

What is the Difference between Friedel–Crafts Alkylation and Acylation?

Friedel–Crafts alkylation differs from Friedel–Crafts acylation in that the former alkylates an aromatic hydrocarbon while the latter acylates the arene. Due to carbocation rearrangement and the tendency for overalkylation of the molecule, which results in unwanted by-products, only specific alkyl benzene compounds can be produced. The acyl group [-C(O)R] generates an acylium ion in the Friedel–Crafts acylation in the presence of AlCl3. The acylium ion assaults the benzene ring, causing it to lose its aromaticity and create a complex intermediate. The AlCl4 ion then takes a proton from the ring, renewing the AlCl3 catalyst and restoring ring aromaticity. The final product is a ring with a ketone mostly attached. Due to the acylium ion’s resonance stabilisation, no rearrangements occur, and deactivation at the ring, preventing further ring replacements.

Conclusion 

Friedel–Crafts reactions are among the most significant in organic chemistry for C-H activation and the creation of C-C bonds. Friedel–Crafts-style alkylations add an alkyl group to an arene molecule, allowing the manufacture of a wide range of industrial goods. The chemistry transforms common chemical feedstocks like benzene into various intermediate and end products. The acid-catalysed reaction of benzene and ethylene to produce ethylbenzene is a typical industrial Friedel Crafts alkylation. Ethylbenzene production is massive, with millions of tonnes produced each year. It is a precursor molecule for the styrene molecule, which is then used to make polystyrene polymers.

Friedel–Crafts reactions with acid chlorides or anhydrides, for example, can require excessive amounts of Lewis acid (i.e., AlCl3) and can result in substantial amounts of corrosive vapour and watery aluminium waste. Our synthetic technique uses an acid that can be quantitatively recycled and an amine component that can be recovered and recycled. As a result, our chemistry reduces the risk of Friedel–Crafts acylation having a negative influence on the environment. We propose a process involving super electrophile production, amide resonance reduction, and acyl cation cleavage.