CHAPTER TWENTY-TWO: ENOLS AND ENOLATES
1. Formation of enolates
a. pKa Aldehyde (≈ 18), Ketone(≈20) and Ester(≈22) -ketoester (≈ 11)
b. hydroxide, alkoxide, LDA comparison
2. Keto-Enol Tautomerism (review)
a. Mechanism in acid (Mechanism 22-5)
b. Mechanism in base (Mechanism 22-4)
LDA vs RO– as base
Kinetic vs thermodynamic control of LDA reaction
Alkylation of Ketones via Enolate (LDA then 1° RX)
Enamines
a. Regioselective formation of less hindered Enamine
b. Mechanism of formation from Ketone via Iminium Ion
c. SN2 Alkylation with unhindered alkyl halides, -haloketones and -haloesters
d. Acylation with acid chlorides and anhydrides to form -ketoketones
7. Halogenation of Ketones
a. In acidic solution: Monohalogenation (reactant ketone more reactive than
product ketone): Mechanism 22-8
b. In basic solution: Polyhalogenation (product more reactive than reactant):
Mechanism 22-6
c. Haloform reaction of methyl ketones (Mechansim 22-7)
8. Halogenation of Carboxylic Acids (Section 22-6)
Hell-Volhard-Zelinsky Rxn: Br2 with PBr3 (Mechanism pg 1060)
3.
4.
5.
6.
9. The Aldol Condensation (carbonyl condensation of ketones and aldehydes)
i. Mechanism in acid and base (Mechanism 22-9 & 22-10)
ii. Self condensation
iii. Elimination (Section 22-8)
iv. Crossed (limitations: multiple products) (Section 22-9)
v. Intramolecular: Cyclizations (Section 22-10)
vi. Reversibile: experimental consequences
10. The Claisen Condensation: Formation of -ketoester products
a. Mechanism (Mechanism 22-12)
b. Subsequent decarboxylation (Mechanism pg 1080)
c. Crossed Claisen: Only one ester can have - H’s (Section 22-14)
d. Variation: Ketone nucleophile + ester electrophile
11. Malonic Ester Synthesis: Using malonic ester (CH2(COOEt)2) with NaOEt then RX
to make -alkylated carboxylic acids (RCH2COOH)
Mechanism:  -alkylation, saponification, acidification, decarboylation
12. Acetoacetic Ester Synthesis: Using ethyl acetoacetate (CH3COCH2COOEt) with
NaOEt then RX to make -alkylated methyl Ketones (CH3COCH2R)
Mechanism:  -alkylation, saponification, acidification, decarboylation
13. Micheal Addition : Conjugate addition of stabilized enols, enamines or Gilman
reagents to -unsaturated carbonylsformation of -dicarbonyl: (Table 22-2;
Section 22-18)
a. Conjugate vs carbonyl addition as function of reversibility
b. Grignard/ Organolithium: carbonyl addition
c. Water/Amines/cyanide stabilized carbon nucleophiles: Conjugate addition
14. Robinson Annulation: Michael (Conjugate) Addition then intramolecular Aldoldehydration to form -unsaturated cyclic ketone (Section 22-19)
LEARNING OUTCOMES:
 Predict the missing product and/or reactant in a relevant chemical reaction involving
carboxylic acid derivatives.
 Use curved-arrow formalism to depict the known mechanism of an organic reaction.
 Devise multi-step syntheses of molecular targets using comprehensive knowledge of
functional group transformations.
 Understand the structural features that relative reactivity in acyl transfer reactions
(interconversion of carboxylic acid derivatives via addn- elimination reactions)
SAMPLE EXAM PROBLEMS:
1. Propose a sequence of steps to effect the following chemical transformation in high
yield:
2. Rank the acidity of the following Bronsted acids from strongest acid (1) to weakest
acid (4)