Aldehyde & Ketone

Nucleophilic Addition to the Carbonyl Group Oxygen Nucleophiles Sulfur Nucleophiles Carbon Nucleophiles Nitrogen Nucleophiles

Reactions at the -Carbon of Aldehyde & Ketone

Reactions at the -Carbon of Carbonyl Compounds Acidity of the -hydrogens Keto-Enol tautomerization Applications

Acidity of the -hydrogens

pKa C2H6 50 C2H4 44 NH3 34 C2H2 25 CH3COCH3 20 C2H5OH 15.9 H2O 15.74 Ph-OH 10 H2CO3 6.5

Keto-Enol Tautomerization Which makes a greater contribution to the hybrid? Keto Enol

A. Interconversion：

Monocarbonyl compounds B. Keto-enol tautomers in equilibrium [enol] K＝ [keto] Monocarbonyl compounds (100%) (extremely small) (99%) (1.5×10-4%) (98.8%) (1.2%)

-dicarbonyl compounds 24% 76% Phenol K  1014

C. Detection: + FeCl3 Purple or blue

D. Formation of enolate: Which “Base”?

enolate

Thermodynamic enolate E. Regioselective Formation of Enolate Anions ? ? Kinetic enolate Thermodynamic enolate Generally: 1. Low temperature gives the kinetic enolate. 2. High temperature, relatively weak base in a protic solvent gives the thermodynamic enolate.

2. In acid condition, the thermodynamic enol is formed predominantly. Two special examples: 1. The kinetically favored enolate can be formed cleanly through the use of diisopropylamide (LDA). 2. In acid condition, the thermodynamic enol is formed predominantly. LDA enol enolate

F. Racemization:

Application alkoxide anions Nucleophilic center Nucleophilic center carbanion Ambident nucleophile

React as an alkoxide anions trapped

React as a carbanion

React as a carbanion 1: Halogenation Haloform reaction

iodoform reaction

React as a carbanion 2: Alkylation side reaction:

solution:

React as a carbanion 3: Aldol Reaction Reversible

easy difficult

How does it work? catalyst Soxhlet Extractor acetone

Crossed Aldol Reaction

Practical Crossed Aldol Reaction

React as a carbanion 4:

glycolysis