Aldehydes/Ketones: Nucleophilic Addition Reactions

Carbonyls and Aldehyde/Ketone  Aldehydes/Ketones = Poor Leaving Group  Acid, Ester, Acid chloride, Amide, Anhydride = Can act as leaving group

Chemistry of Carbonyls Nucleophilic O: React with acids and electrophiles Electrophilic C: React with bases and nucleophiles

Nomenclature of aldehydes and ketones ending –e with –al  Simple aldehyde: replace the parent ending –e with –al carboxaldehyde  Complex (ring attached): carboxaldehyde  Ketone: Find the longest chain with C=O Replace –e with -one

Examples

Synthesis of Aldehydes and Ketones  Refer to alcohol chapter Oxidation of primary alcohol with PCC Oxidation of secondary alcohol Hydration of terminal alkynes Friedel-Crafts acylation

Oxidation of aldehydes  Tollen’s reagent for aldehyde testing

Nucleophilic Addition Reaction  Common nucleophilic addition reaction  To the carbonyl carbon Reduction Hydration Acetal formation Grignard addition Imine formation

 Guidelines Under basic (in presence of –OH, -OR) Negatively charged intermediates Under acidic (H+): positively charged intermediate Nucleophilic Addition Reaction

Reduction in Org. Chem. And Biochemistry Reducing reagent in Org. Chem. LiAlH4 >> NaBH4

Nucleophilic Addition of Water: Hydration  H to O rule: When ROH adds to C=O, H goes to oxygen of C=O (while) RO goes to carbon of C=O To form gem-diol or acetal

Nucleophilic Addition of Water: Hydration

 Sequential reaction of hemiacetal and acetal through oxonium ion Nucleophilic Addition of Alcohol

Hemiacetal formation in nature

Acetal as Protecting Group in Org. Syn.

Addition of Amines to Imines Imine formation as fundamentals of nitrogen assimilation in biosystems

Nucleophilic addition of Grignard reagents Alcohol formation Grignard reagent Formaldehyde:Primary alcohol Grignard reagent +Formaldehyde:Primary alcohol Aldehyde:Secondary alcohol Ketone:Tertiary alcohol Limitation:React with: -CHO, -COR, -CONR 2, -CN, -NO 2, -SO 2 R Decomp. by: -OH, -NH, -SH, -COOH

Conjugate addition of ,  -unsaturated ketone/aldehyde