Question

Show all the steps in the acid-catalyzed formation of a cyclic acetal from ethylene glycol and an aldehyde or ketone.

Short answer

The cyclic acetal is formed through six steps involving protonation, nucleophilic attack, proton transfer, water elimination, another nucleophilic attack, and deprotonation.

Step-by-step solution

Protonation of the Carbonyl Oxygen

The acid catalyst donates a proton ( n n n n ) to the oxygen of the carbonyl group on the aldehyde or ketone. This increases the electrophilicity of the carbonyl carbon, making it more susceptible to nucleophilic attack.

Nucleophilic Attack by Ethylene Glycol

The nucleophilic oxygen atom in one of the hydroxyl groups of ethylene glycol attacks the protonated carbonyl carbon, forming a tetrahedral intermediate. This step involves the bonding of the ethylene glycol to the carbonyl carbon.

Proton Transfer

A proton transfer occurs, typically facilitated by the solvent or acid catalyst, moving a proton to the hydroxyl group that originally attacked the carbonyl carbon, forming a good leaving group (water).

Formation and Departure of Water

The intermediate eliminates a molecule of water, resulting in the formation of a carbocation intermediate which is stable due to resonance.

Second Nucleophilic Attack by Ethylene Glycol

The remaining hydroxyl group of ethylene glycol attacks the carbocation, forming a second tetrahedral intermediate. This step further stabilizes the intermediate by forming a bond between the carbon and the oxygen of the second hydroxyl group.

Deprotonation and Acetal Formation

In the final step, a base in the solution removes a proton from the oxygen that attacked the carbocation, leading to the formation of a stable cyclic acetal. This completes the reaction by regenerating the acid catalyst.

Key concepts

Acid-Catalysis

In many chemical reactions, including the formation of a cyclic acetal, an acid catalyst plays a pivotal role. Acid-catalysis involves the use of an acidic substance to speed up the reaction. The acid donates a proton ( \( H^+ \) ) which can enhance the reactivity of other molecular components.
This is crucial in making certain atoms more electrophilic or positively charged, making them more attractive to nucleophiles. For example, in the formation of a cyclic acetal, the acid catalyst donates a proton to the carbonyl oxygen.
This protonation increases the electrophilicity of the carbonyl carbon, thus enabling a more effective nucleophilic attack by substances like ethylene glycol.

Nucleophilic Attack

A nucleophilic attack is a fundamental concept in organic chemistry reactions. It involves a nucleophile, a species rich in electrons, attacking an electrophilic center, which is electron-deficient.
In our reaction scenario with cyclic acetal formation, ethylene glycol acts as the nucleophile. The oxygen atom in one of the glycol’s hydroxyl groups attacks the electrophilic carbon of the protonated carbonyl group.

• This attack results in the formation of a tetrahedral intermediate.
• Nucleophilic attack is driven by the nucleophile's desire to share its electron pair with a suitable electrophile.

Such attacks are typically promoted in acid-catalyzed conditions as seen here.

Protonation

Protonation is the process where a proton is added to a molecule, essentially making it more positively charged. During the cyclic acetal formation, protonation serves two key purposes.
Firstly, the acid catalyst donates a proton to the carbonyl oxygen, enhancing the carbonyl carbon’s electrophilicity. This makes it more amenable to a nucleophilic attack from ethylene glycol.

• Protonation is also involved in the stabilization of intermediates.
• It plays a role in converting hydroxyl groups into good leaving groups by protonating them to water.

Thus, protonation in such acid-catalyzed mechanisms is crucial for intermediate transformations.

Carbocation Intermediate

In reaction mechanisms, intermediates often play key roles in transitioning to the next phase. A carbocation intermediate is a positively charged species with an empty p-orbital.
During the formation of a cyclic acetal, a carbocation is generated after the expulsion of water. This occurs post-nucleophilic attack and subsequent loss of a leaving group.

• Carbocations are stabilized by resonance, which can delocalize the positive charge.
• They are highly reactive and serve as excellent targets for a second nucleophilic attack, which completes the cyclic acetal formation process.

Understanding carbocation behavior is essential in predicting the course and feasibility of organic reactions.