Question

Benzene and alkyl-substituted benzenes can be hydroxylated by reaction with \(\mathrm{H}_{2} \mathrm{O}_{2}\) in the presence of an acidic catalyst. What is the structure of the reactive electrophile? Propose a mechanism for the reaction.

Short answer

The reactive electrophile is \(\mathrm{HO}^+\), facilitating hydroxylation via electrophilic aromatic substitution.

Step-by-step solution

Identify the Electrophile

In the presence of an acid, hydrogen peroxide (\(\mathrm{H}_2\mathrm{O}_2\)) forms the electrophile, which is the perhydroxyl cation (\(\mathrm{HO}^+\)), also known as the hydroperoxonium ion. This happens because the acid donates a proton to one of the oxygen atoms in \(\mathrm{H}_2\mathrm{O}_2\), enhancing its electrophilic nature.

Electrophile Activation

The protonation step can be shown as \( \mathrm{H}_2\mathrm{O}_2 + \mathrm{H}^+ \rightarrow \mathrm{HO}^+ + \mathrm{H}_2\mathrm{O} \). Here, the perhydroxyl cation (\(\mathrm{HO}^+\)) is generated. This step activates \(\mathrm{H}_2\mathrm{O}_2\) to become a more effective electrophile capable of reacting with aromatic rings.

Electrophilic Aromatic Substitution

In the actual reaction mechanism, the electrophile \(\mathrm{HO}^+\) attacks the aromatic benzene ring, forming a sigma complex (also known as an arenium ion). This step temporarily disrupts the ring's aromaticity as \(\mathrm{HO}^+\) binds to a carbon atom.

Aromaticity Restoration

To restore aromaticity in the benzene ring, deprotonation occurs. A proton is removed from the carbon atom adjacent to where \(\mathrm{HO}\) bonded. This reform the double bond in the aromatic ring, giving the hydroxyl-substituted benzene and completing the reaction.

Complete the Reaction

Thus, the reaction efficiently hydroxylates benzene to phenol, and alkyl-substituted benzenes to their hydroxyl counterparts using hydrogen peroxide in an acidic medium, following the pathway of electrophilic aromatic substitution facilitated by the strong electrophile \(\mathrm{HO}^+\).

Key concepts

Hydroxylation

Hydroxylation is the process of introducing a hydroxyl group, \text{OH}, into an organic compound, often an aromatic ring. This reaction is crucial in the modification of hydrocarbons, including benzene, to form alcohol derivatives like phenols. In our exercise, we are looking at hydroxylating benzene using hydrogen peroxide \(\mathrm{H}_{2}\mathrm{O}_{2}\) as the oxidizing agent. This process requires an acidic catalyst to proceed efficiently, causing the formation of a reactive electrophile. \Hydroxylation can be seen as a part of electrophilic aromatic substitution reactions when an aromatic compound such as benzene is involved. \

• Hydroxylation helps introduce functional groups that can alter the physical and chemical properties of aromatic compounds.
• In biological systems, hydroxylation is used in metabolic pathways to increase solubility for excretion.

Understanding the role of hydrodynamics and activation steps in these reactions can be pivotal for synthetic chemistry and pharmaceutical developments.

Reaction Mechanism

The reaction mechanism for hydroxylating benzene with peroxides, specifically hydrogen peroxide \(\mathrm{H}_{2}\mathrm{O}_{2}\), involves multiple steps and intermediates. It begins with the formation of the electrophile, and here's how it proceeds: \

Formation of the Electrophile

\In the presence of an acidic catalyst such as sulfuric acid, hydrogen peroxide accepts a proton from the acid, forming the perhydroxyl cation \(\mathrm{HO}^+\), which then acts as a strong electrophile. This enhanced electrophilic nature is crucial for the next reaction step with benzene. \

Electrophilic Attack

\The \(\mathrm{HO}^+\) ion attacks the benzene ring, forming a sigma complex. This step is energetically favorable because it allows the formation of a stable intermediate, although it temporarily disrupts the aromaticity of the benzene ring. \

• The formation of the arenium ion is an essential aspect of this step.
• This resembles the initial stages of classic electrophilic aromatic substitution reactions.

Restoration of Aromaticity

\Following the formation of the sigma complex, the hydrogen atom is removed, usually by base abstraction, from the carbon atom adjacent to the new bond. This removal allows for the reformation of the double bond, restoring the aromaticity of the compound immediately, yielding a hydroxylated product.

Perhydroxyl Cation

The perhydroxyl cation \(\mathrm{HO}^+\) plays a central role in the hydroxylation mechanism by serving as the primary electrophile. Produced via protonation of hydrogen peroxide, this cation is highly reactive. This reactivity is a result of the oxygen atom bearing a positive charge that seeks electrons to neutralize this charge, hence making it capable of attacking electron-rich centers, like the carbon atoms in benzene. \

• The perhydroxyl cation is comparable to other common electrophiles used in similar reactions, such as the acylium ion (\(\mathrm{RCO}^+\)).
• Much like other carbocations involved in electrophilic substitutions, \(\mathrm{HO}^+\) formation is facilitated in acidic environments.

\The understanding of how the perhydroxyl cation functions is vital for mastering electrophilic aromatic substitution reactions. It highlights the importance of the proton as a catalyst that activates otherwise neutral molecules into reactive electrophiles.