Intermolecular Aldol Reaction

Definition

The intermolecular aldol reaction is a type of carbon-carbon bond-forming reaction that occurs between two separate carbonyl-containing compounds, resulting in the formation of a new β-hydroxy carbonyl product. This reaction is a key step in many organic synthesis pathways and is widely used in the construction of more complex molecules.

5 Must Know Facts For Your Next Test

1. The intermolecular aldol reaction occurs between two separate carbonyl-containing compounds, unlike the intramolecular aldol reaction which involves a single carbonyl-containing compound.
2. The reaction is typically catalyzed by a base, which generates the nucleophilic enolate from one of the carbonyl compounds.
3. The enolate then attacks the electrophilic carbonyl carbon of the other carbonyl compound, forming a new carbon-carbon bond and a β-hydroxy carbonyl intermediate.
4. Subsequent dehydration of the β-hydroxy carbonyl intermediate can lead to the formation of an α,β-unsaturated carbonyl compound in the aldol condensation step.
5. Intermolecular aldol reactions are widely used in organic synthesis to construct more complex molecules with new carbon-carbon bonds and functionalities.

Review Questions

• Describe the key steps involved in an intermolecular aldol reaction.
  • The intermolecular aldol reaction consists of two main steps: aldol addition and aldol condensation. In the aldol addition step, a nucleophilic enolate, generated from one carbonyl compound, attacks the electrophilic carbonyl carbon of another carbonyl compound, forming a new carbon-carbon bond and a β-hydroxy carbonyl intermediate. This is followed by the aldol condensation step, where the β-hydroxy carbonyl intermediate undergoes dehydration to form an α,β-unsaturated carbonyl product.
• Explain the role of the enolate in the intermolecular aldol reaction and how it is formed.
  • The enolate is a key intermediate in the intermolecular aldol reaction, as it acts as the nucleophile that attacks the electrophilic carbonyl carbon. The enolate is typically generated by the treatment of a carbonyl compound with a strong base, which removes a proton from the α-carbon, resulting in the formation of a negatively charged, nucleophilic enolate species. This enolate then attacks the carbonyl carbon of another carbonyl compound, initiating the aldol addition step and allowing the formation of the new carbon-carbon bond.
• Discuss the significance of the intermolecular aldol reaction in organic synthesis and the types of products that can be obtained.
  • The intermolecular aldol reaction is a powerful tool in organic synthesis, as it allows for the construction of more complex molecules by forming new carbon-carbon bonds. The reaction can be used to introduce a variety of functional groups, such as alcohols, ketones, and α,β-unsaturated carbonyl compounds, depending on the specific reaction conditions and the starting materials employed. The versatility of the intermolecular aldol reaction makes it a valuable synthetic method for the preparation of a wide range of organic compounds, including natural products, pharmaceuticals, and other important chemical entities.

Related terms

Aldol Addition:

The initial step of the aldol reaction where a nucleophilic enolate attacks an electrophilic carbonyl to form a new carbon-carbon bond and a β-hydroxy carbonyl intermediate.

Aldol Condensation:

The second step of the aldol reaction where the β-hydroxy carbonyl intermediate undergoes dehydration to form an α,β-unsaturated carbonyl compound.

Enolate:

A reactive intermediate formed when a carbonyl compound is treated with a strong base, possessing a nucleophilic carbon and a negatively charged oxygen.