Question

Prepare a ketone from each of the following precursors by the Friedel-Crafts acylation method.

Short answer

In the Friedel-Crafts acylation method, the given precursors benzene, toluene, and anisole were reacted with acetyl chloride in the presence of AlCl3 catalyst. This resulted in the formation of the ketones acetophenone from benzene, 1-phenyl-1-propanone from toluene, and either 4'-methoxyacetophenone or 2'-methoxyacetophenone from anisole.

Step-by-step solution

1. Identify the precursor molecules and choose an appropriate acyl halide

Given precursors: 1. Benzene 2. Toluene 3. Anisole We can choose: Acyl halide - Acetyl chloride (CH3COCl) Catalyst - Aluminum chloride (AlCl3)

2. Draw the reaction mechanism for benzene

For benzene: 1. Benzene reacts with acetyl chloride in the presence of AlCl3 catalyst, forming an acylium ion intermediate and a byproduct of HCl. 2. The acylium ion then reacts with the benzene ring, forming a new carbon-carbon bond. 3. Finally, the product is a ketone, acetophenone (C6H5COCH3). \[ \text{Benzene} + \text{CH}_3\text{COCl} \xrightarrow[\text{AlCl}_3]{} \text{C}_6\text{H}_5\text{COCH}_3 \]

3. Draw the reaction mechanism for toluene

For toluene: 1. Toluene reacts with acetyl chloride in the presence of AlCl3 catalyst, forming an acylium ion intermediate and a byproduct of HCl. 2. The acylium ion then reacts with the toluene ring at ortho/para positions, forming a new carbon-carbon bond. 3. Finally, the product is a ketone, 1-phenyl-1-propanone (C6H5C(O)CH3). \[ \text{Toluene} + \text{CH}_3\text{COCl} \xrightarrow[\text{AlCl}_3]{} \text{C}_6\text{H}_5\text{C(O)CH}_3 \]

4. Draw the reaction mechanism for anisole

For anisole: 1. Anisole reacts with acetyl chloride in the presence of AlCl3 catalyst, forming an acylium ion intermediate and a byproduct of HCl. 2. The acylium ion then reacts with the anisole ring at ortho/para positions, forming a new carbon-carbon bond. 3. Finally, the product is a ketone, 4'-methoxyacetophenone or 2'-methoxyacetophenone. \[ \text{Anisole} + \text{CH}_3\text{COCl} \xrightarrow[\text{AlCl}_3]{} \text{4'-methoxyacetophenone} \text{ or } \text{2'-methoxyacetophenone} \] In summary, Friedel-Crafts acylation has been used to synthesize the following ketones from the given precursors: 1. Acetophenone from benzene 2. 1-phenyl-1-propanone from toluene 3. 4'-methoxyacetophenone or 2'-methoxyacetophenone from anisole

Key concepts

Ketone Synthesis

Ketone synthesis through the Friedel-Crafts acylation process is a fascinating method in organic chemistry that involves the introduction of an acyl group into an aromatic ring. This reaction is primarily utilized to create ketones from aromatic hydrocarbons. The process is particularly popular because it provides an efficient route to synthesize ketones with high selectivity. It involves reacting aromatic compounds such as benzene or substituted benzenes with acyl chlorides or anhydrides, in the presence of a Lewis acid catalyst.

• Benzene reacts to give acetophenone.
• Toluene yields 1-phenyl-1-propanone.
• Anisole forms methoxyacetophenone derivatives.

Cleaving a carbon-halogen bond in the presence of a catalyst and attaching a carbonyl group to the aromatic ring essentially facilitates this transformation. The result is a structurally diverse range of ketones which are significant in various industrial and pharmaceutical applications.

Reaction Mechanism

The reaction mechanism of Friedel-Crafts acylation can initially seem complex but is straightforward upon closer inspection. The process starts by generating an acylium ion from the acyl chloride. This occurs when the acyl chloride is exposed to a Lewis acid catalyst such as aluminum chloride (\(\text{AlCl}_3\)).
The Lewis acid transforms the acyl chloride into a highly reactive intermediate: \[\text{RCOCl} + \text{AlCl}_3 \rightarrow \text{RCO}^+ + \text{AlCl}_4^-\] The acylium ion, which is a resonance-stabilized species, then reacts with the \(\pi\)-electrons of the aromatic ring to form a carbocation intermediate. Finally, a series of proton transfers and rearrangement results in the aromatic ketone. The regeneration of the aromatic system and removal of the catalyst by hydrolysis marks the end of the mechanism, completing the formation of the desired ketone product. This sequence of steps underscores the specificity and precision of Friedel-Crafts acylation.

Acylium Ion Intermediate

The acylium ion is a crucial intermediate in the Friedel-Crafts acylation. Recognizable by its linear geometry and positive charge, it plays a pivotal role in the successful completion of the reaction. This species is generated when an acyl chloride reacts with \(\text{AlCl}_3\), as the catalyst draws electrons away from the acyl chloride, creating the electrophilic acylium ion. The acylium ion is stabilized by resonance, with the positive charge delocalizing across the carbon and oxygen atoms of the carbonyl group.
Its primary function is to attack the \(\pi\)-electrons of the aromatic ring, a process that forms a carbocation. This interaction presents the possibility of selectively controlling the position of acyl group attachment by choosing different aromatic substrates. Understanding the acylium ion's behavior is fundamental in the Friedel-Crafts acylation process as it defines the pathway and efficiency of ketone formation.

Organic Chemistry Education

Friedel-Crafts acylation offers valuable lessons in organic chemistry education, providing insights into reaction mechanisms, catalysis, and electrophilic aromatic substitution. It emphasizes the practical aspects of chemical synthesis, crucial for understanding molecular assembly in both academic and industrial settings.
Teaching this process exposes students to:

• The concept of electrophile generation and reaction with aromatic rings.
• The role of Lewis acids in catalysis.
• The importance of reaction conditions and substrate specificity.

With practical applications spanning from pharmaceuticals to perfumes, learning Friedel-Crafts acylation enriches the students' grasp of synthetic chemistry. By exploring this specific reaction type, students also develop an appreciation for the delicate balance needed in chemical reactions to achieve desired products efficiently and economically.