Nucleophilic Addition to the Carbonyl

CHEMISTRY 226 NUCLEOPHILIC ADDITION TO THE CARBONYL GROUP 1. General Reaction: R C OH R' Nu H+ or OH-+C O R'R H Nu ? Requires either acid or base catalysis (except for strong nucleophiles). ? A new bond is formed at carbon. ? The trigonal carbon is converted to a tetrahedral carbon. ? Net effect: addition of H-Y across the C-O double bond. 2. Examples of addition of weak nucleophiles to the carbonyl group: conditions) to acetal under acidic [an imine (Schiff base)] (Nu = OH) (-H2O) NCH3 CR R' pH = 5 (a hydrate)R C R' OH OH H+ or OH- H+ or OH- (a hemiacetal, converted R C R' OH OCH3(Nu = OCH3) C O R'R + CH3OH + CH3NH2 + H2O 3. Mechanisms of nucleophilic addition to the carbonyl: a. Acid-catalyzed hydration R C R' OH OH R C OH OH2 R'C O R'R C R'R OH OH 2+ H+ - H+ b. Base-catalyzed hydration H2O R C R'OH OH R C R' O OH C O R'R + OH OH c. Acid-catalyzed hemiacetal formation R C R' OH OCH3 R C R' OH O CH 3H C OH R'RC O R'R + H+ CH3OH - H+ d. Base catalyzed hemiacetal formation R C OH R' OCH3 CH3OHR CO R' OCH3 R C O R' OCH3 + CH3O e. Formation of an imine R C NCH3 R' R C NHCH3 R' H+ R C OH2 R' NHCH3 R C OH NHCH3 R'R C OH R' NHCH3 H H R C O R' H+ R C O R' CH3NH2 - H+ - H2O- H+ 4. Conversion of hemiacetals to acetals (acid-catalyzed only): C R' OCH3 OCH3 R C R' OCH3 OCH3 R H R C R' OCH3 R C OCH3 R' OH2H+ R C OH OCH3 R' - H2O CH3OH - H+ 5. General mechanistic comments: ? All steps are reversible. Therefore all reactions are reversible ? Acid catalysis increases the reactivity of the carbonyl group; basic catalysis increases the reactivity of the nucleophile. ? All cationic intermediates are either resonance stabilized or have full octets of electrons. Anionic species always have the charge on oxygen. Nucleophilic addition to the carbonyl