Which Of The Following Compounds Does Not Undergo Friedel-crafts Reaction

Which of the Following Compounds Does Not Undergo Friedel-Crafts Reaction?

The Friedel-Crafts reaction, a cornerstone of organic chemistry, allows for the alkylation and acylation of aromatic rings. However, not all aromatic compounds are equally susceptible to this powerful transformation. Understanding why certain compounds resist Friedel-Crafts reactions is crucial for synthetic planning and predicting reaction outcomes. This in-depth article explores the limitations of the Friedel-Crafts reaction, focusing on the structural features that prevent its successful application. We'll examine several classes of compounds and delve into the mechanistic reasons behind their inertness.

Understanding the Friedel-Crafts Reaction Mechanism

Before examining compounds that resist Friedel-Crafts reactions, let's briefly review the mechanism. The reaction proceeds through the formation of an electrophilic species, typically a carbocation (in Friedel-Crafts alkylation) or an acylium ion (in Friedel-Crafts acylation). This electrophile is generated by the reaction of a Lewis acid catalyst, such as aluminum chloride (AlCl₃) or ferric chloride (FeCl₃), with an alkyl halide or acyl halide. This highly reactive electrophile then attacks the electron-rich aromatic ring, leading to the formation of a sigma complex (arenium ion). Subsequent deprotonation regenerates the aromaticity and yields the alkylated or acylated product.

The key to understanding the limitations lies in recognizing that this mechanism requires a highly reactive electrophile and an electron-rich aromatic ring. Anything that interferes with either of these components will hinder or completely prevent the reaction.

Compounds That Do Not Undergo Friedel-Crafts Reactions

Several classes of aromatic compounds are unreactive towards Friedel-Crafts reactions. These include:

1. Deactivated Aromatic Rings:

Aromatic rings bearing strong electron-withdrawing groups (EWGs) are significantly deactivated towards electrophilic aromatic substitution, including Friedel-Crafts reactions. These EWGs reduce the electron density of the aromatic ring, making it less susceptible to electrophilic attack. Examples of strong EWGs include:

• Nitro groups (-NO₂): The nitro group is a very strong EWG due to resonance and inductive effects. Nitrobenzene, for example, is completely unreactive towards Friedel-Crafts reactions. The strong electron withdrawal makes the ring highly deactivated.

• Carboxyl groups (-COOH): Benzoic acid and its derivatives are similarly resistant to Friedel-Crafts reactions because of the electron-withdrawing nature of the carboxyl group.

• Sulfonic acid groups (-SO₃H): Benzenesulfonic acid and related compounds are also significantly deactivated due to the strong electron-withdrawing effect of the sulfonic acid group.

• Cyano groups (-CN): The cyano group is another powerful EWG, rendering the aromatic ring less nucleophilic and resistant to Friedel-Crafts reactions.

Why Deactivation Prevents Friedel-Crafts Reactions: The electron-withdrawing groups significantly reduce the electron density in the aromatic ring. This makes the ring less nucleophilic, thus hindering the attack of the electrophile. Furthermore, the strong electron withdrawal can even react with the Lewis acid catalyst, forming a complex and preventing the formation of the active electrophile.

2. Sterically Hindered Aromatic Rings:

Even with an activated aromatic ring, steric hindrance can prevent the Friedel-Crafts reaction. Bulky substituents on the aromatic ring can physically block the approach of the electrophile, preventing the formation of the sigma complex. This is particularly true for Friedel-Crafts alkylation, where the bulky alkyl carbocation is more susceptible to steric hindrance than the smaller acylium ion in Friedel-Crafts acylation.

Examples include:

• Mesitylene (1,3,5-trimethylbenzene): Although activated by three methyl groups, the steric bulk of these groups makes Friedel-Crafts alkylation difficult. Acylation is generally more successful due to the smaller size of the acylium ion.

• Polyalkylated benzenes: Aromatic rings with multiple bulky alkyl groups experience significant steric hindrance, limiting their reactivity in Friedel-Crafts reactions.

Why Steric Hindrance Prevents Friedel-Crafts Reactions: The large size of the substituents and electrophile prevent the proper alignment required for the formation of the sigma complex. The transition state leading to the formation of this intermediate is energetically unfavorable due to steric strain.

3. Aromatic Rings with Reactive Functional Groups:

Certain functional groups on the aromatic ring can undergo side reactions with the Friedel-Crafts reagents, preventing the desired alkylation or acylation. These include:

• Phenols (-OH): Phenols are readily reactive with Lewis acids, leading to complex formation and preventing the Friedel-Crafts reaction. The hydroxyl group can also react with the electrophile, leading to unwanted side products.

• Amines (-NH₂): Aromatic amines react with Lewis acids forming complexes which block the desired Friedel-Crafts reaction. Moreover, the lone pair on the nitrogen atom can compete with the aromatic π-system for the electrophile.

• Aldehydes (-CHO) and Ketones (-C=O): These groups can react with the Lewis acid catalyst, interfering with the formation of the electrophile. Also, these groups can be prone to other reactions under Friedel-Crafts conditions.

Why Reactive Functional Groups Prevent Friedel-Crafts Reactions: The presence of these groups leads to competitive reactions with the reagents or catalyst. The preferential reaction with these groups over the aromatic ring prevents the Friedel-Crafts reaction from occurring.

4. Compounds Undergoing Rearrangements:

Friedel-Crafts alkylation is often accompanied by carbocation rearrangements. This can lead to a mixture of products, making it difficult to obtain a single desired product. Highly branched alkyl halides, in particular, are prone to these rearrangements. This unpredictable nature limits the usefulness of Friedel-Crafts alkylation with such substrates.

Why Rearrangements Prevent Predictable Friedel-Crafts Reactions: The instability of certain carbocations leads to rearrangements, resulting in unexpected products and low yields of the desired compound. This makes it difficult to control the selectivity of the reaction.

Conclusion: Choosing the Right Approach

The Friedel-Crafts reaction is a powerful tool in organic synthesis. However, its success depends heavily on the nature of the aromatic substrate. Understanding the limitations imposed by deactivated rings, steric hindrance, reactive functional groups, and potential for carbocation rearrangements is essential for effectively applying this reaction. Careful consideration of these factors is crucial for designing successful synthetic strategies and predicting reaction outcomes. Choosing alternative methods like the use of organometallic reagents for similar transformations may be necessary for compounds that are unsuitable for the Friedel-Crafts reaction. The selection of the appropriate synthetic strategy depends greatly on the specific substrate and desired product. This detailed examination highlights the necessity of understanding reaction mechanisms and the factors that influence reactivity to successfully navigate the landscape of organic synthesis.