Reactions of Ketones and Aldehydes

Reduction Reactions of Ketones and Aldehydes

  • General Concept: Ketones and aldehydes can be reduced to alcohols using various reagents.

1. Reduction with Sodium Borohydride (NaBH4)

  • Reagent: Sodium borohydride (NaBH4)
  • Process:
  • Ketones and aldehydes react with NaBH4 to form alcohols.
  • Example: A ketone is reduced to a secondary alcohol, while an aldehyde is reduced to a primary alcohol.
  • Mechanism:
  • The sodium ion is a spectator, and boron has a negative charge.
  • The hydride ion (H-) from boron attacks the carbonyl carbon (C=O), creating an alkoxide ion.
  • In the presence of H3O+, the alkoxide ion gains a proton, leading to alcohol formation.

2. Reduction with Lithium Aluminum Hydride (LiAlH4)

  • Reagent: Lithium aluminum hydride (LiAlH4)
  • Process:
  • A stronger reducing agent compared to NaBH4, capable of reducing esters and carboxylic acids.
  • Example: Reduces an aldehyde to a primary alcohol.
  • Mechanism:
  • The hydride from LiAlH4 attacks the carbonyl carbon, yielding an alcohol after the formation of an alkoxide and subsequent protonation.

3. Reaction with Esters and Acid Chlorides

  • Esters: NaBH4 cannot reduce esters, but LiAlH4 can. The product is an alcohol.
  • Acid Chlorides:
  • Can be reduced by either NaBH4 or LiAlH4.
  • NaBH4 reduces acid chlorides to alcohols, expelling chloride ions as by-products.
  • LiAlH4 can reduce acid chlorides to primary alcohols.

4. Mechanism of Acid Chloride Reduction

  • Reaction with NaBH4:
  • The hydride ion attacks the carbonyl, forming a tetrahedral intermediate, which collapses to form an aldehyde.
  • A second hydride attack by sodium borohydride converts the aldehyde to a primary alcohol.
  • Deactivated LiAlH4:
  • LiAlH4 with one hydrogen and three R groups will stop at the aldehyde level when reacted with acid chlorides.

5. Reduction of Carboxylic Acids and Amides

  • Carboxylic Acids: Reduced to primary alcohols by LiAlH4.
  • Amides: Reduced to primary amines by LiAlH4.

Reactions with Grignard Reagents

  • Grignard Reagents:
  • Formed from alkyl halides and magnesium; high nucleophilicity allows them to attack carbonyls.
  • Aldehydes with Grignard Reagents: Produce secondary alcohols upon reaction.
  • Ketones with Grignard Reagents: Produce tertiary alcohols upon reaction.

Formation of Imine and Enamine

  • Imine Formation:
  • Reaction with primary amines; water is removed leading to double bonds between carbon and nitrogen.
  • Enamine Formation:
  • Reaction with secondary amines; results in carbon-nitrogen and an additional carbon-carbon double bond.

Mechanism Overview

  • Imine Formation:
  • Amine attacks the carbonyl; steps involve the formation and loss of water.
  • Enamine Formation:
  • Similar initial steps followed by carbon-carbon bond formation.

Reductive Amination

  • Process:
  • Converts ketones to amines through intermediate formation and reduction steps.

Reaction Conditions and Mechanism Insights

  • Direct vs. Conjugate Addition:
  • Direct: Strong nucleophiles attack the carbonyl carbon.
  • Conjugate: Weaker nucleophiles attack the beta carbon.
  • Factors Influencing Addition: Nucleophilic strength and steric hindrance dictate product selectivity in reactions with carbonyls.

Bayer-Villiger Oxidation Reaction

  • Mechanism: Ketone reacts with peroxy acid to form esters.
  • Migratory Aptitude: Influences product formation by determining which carbon receives the oxygen.

Conclusion

  • Ketones and aldehydes are versatile functional groups with many reactions relying on their carbonyl functionality, involving various conditions and reagents for transformations to alcohols, amines, and other products.