0.7 Friedel-crafts reaction  (Page 6/3)

Lab 4: friedel-crafts reaction: acetylation of ferrocene

Objective

This experiment features on electrophilic aromatic substitution reaction. In this reaction an electrophile replaces a hydrogen atom in an aromatic compound forming a new carbon-carbon bond.

Background information

As noted in earlier experiments, a unifying theme of synthetic organic chemistry is the construction of carbon-carbon bonds. Such bond-forming reactions allow the elaboration of simpler precursors into more complicated organic structures. Electrophilic aromatic substitution reactions feature an electrophile replacing a hydrogen atom in an aromatic compound and can form a new carbon-carbon bond if done with an electrophilic carbon species. Such reactions were discovered in 1877 by Charles Friedel and James Crafts and are collectively known as Friedel-Crafts reactions. These reactions may be used to introduce both alkyl ("Friedel-Crafts alkylation") and acyl groups ("Friedel-Crafts acylation").

Friedel-crafts acylation reaction:

Friedel-Crafts acylation represents a powerful and effective way to introduce new carbon-carbon bonds into aromatic compounds. It has been extensively exploited as a synthetic tool since its discovery. However, the reaction is not without limitations. A strong Lewis acid, often aluminum chloride which is corrosive and gives off HCl upon contact with moist air, is required in greater than stoichiometric amounts leading to the generation of considerable quantities of acidic and aluminum contains waste. Common solvents for Friedel-Crafts acylation reactions include halogenated methanes (e.g., dichloromethane) or carbon disulfide, representing environmental and/or human health risks. In this experiment, you will use a more benign catalyst, phosphoric acid, to catalyze the Friedel-Crafts acylation reaction. No organic solvents are used, although one of the reactants, acetic anhydride, is used in excess and thus may serve the role as a solvent in this reaction. Unfortunately, these acylation conditions are not general - it is the relatively high reactivity of ferrocene compared to simpler aromatic substrates that allows the replacement of ${\text{AlCl}}_3$ with phosphoric acid. Discovery of new Friedel-Crafts-like reaction chemistry applicable to simple benzene derivatives remains an area of ongoing investigation.

As the following mechanism indicates, Friedel-Crafts acylation involves the formation of an acylium ion as the active electrophilic species. The reactive acylium ion is generated from an acyl halide or anhydride by treatment with a Lewis acid. Aluminum chloride is commonly used for this purpose. Although ${\text{AlCl}}_3$ could potentially affect the catalysis of the Friedel-Crafts acylation reaction, the product, a ketone, is sufficiently basic enough to interact strongly with ${\text{AlCl}}_3$ such that more than one equivalent of ${\text{AlCl}}_3$ is required. The ${\text{AlCl}}_3$ is removed in the aqueous workup step by hydrolysis to HCl and aluminum hydroxide.

The Friedel-Crafts acylation reaction

Some important points:

• Acyl groups - carbonyl attached to an H or an alkyl group.