Vince Lambert H.

Padilla, RPh
Instructor 1
At the end of this session, you should be able to:
 Distinguish Enols and Enones from each other
 Relate the chemical properties of enolates with the reactions they can
undergo
 Identify the reagents used and conditions required in the reactions
involving enolates and other carbon nucleophiles
 Determine the type of reaction that will occur given the substrate, the
reactant, and the reaction conditions, as well as predict the product of
the reaction
 Draw the reaction mechanism of these reactions
I. Enols and Enolate Ions
II. Halogenations of the α-Carbon
III. Alkylation of More Stabilized Anions
IV. Aldol Condensation
V. Conjugate Additions
VI. Ester Enolates
VII.β-Dicarbonyl Compounds
 Carbonyl Functional Group
 Acidity of Aldehydes and Ketones: Enolates
 Keto-Enol Equilibria
 Consequences of Enolization
 O O H
Carbonyl group

R H+/OH-
α-Carbon C R C
C R’ C R’

H H H
α-Hydrogen
 Formation of Enolate ions a.k.a.
 R O H

R C C R

B H
 Identify the most acidic H in each of the following molecules.
Give the structure of the enolate ion arising from deprotonation.
a) Acetaldehyde
b) Propanal
c) Acetone
d) 4-heptanone
e) Cyclopentanone
 Ambident behavior: C-alkylation and O-protonation
 Give the products of reaction of cyclohexanone enolate with:
a) Iodoethane
b) Chlorotrimethylsilane
 Keto-Enol tautomerization
 Base- and Acid-catalyzed
 R O H B

R C C R

B H
 R O H

R C C R

H
 Enol form of acetaldehyde is more stable than that of acetone
 Deuterium exchange

 Stereoisomer interconversion

 Racemization
 Write the products (if any) of D incorporation by the
treatment of the following compounds with D2O-NaOD
a) Cycloheptanone
b) 3,3-dimethylbutanone
c) 2,2-dimethylpropanal
d)
O

O
 Acid-catalyzed α-Halogenation
 Base-catalyzed α-Halogenation
 Extent of completion depends on the catalyst used
 Stops after one halogenation
 Rate is independent of X2 concentration
 Involves 3 steps:
1. Enolization (rate-determining step)
2. Halogen attack/Electrophilic attack
3. Deprotonation
 H O H

H C C R

H
Br Br
 All α-H are replaced before another molecule of starting material
is halogenated
Br Br O
B H

Br B BrH C H C R

B H O Br H
Br
 Write the products of acid- and base-catalyzed bromination
of cyclohexanone
 Alkylation of Aldehydes and Ketones
 Alkylation of Enamine
 Nu- substitution
 Complicated by several factors:
 Normally feasible using only halomethanes or 1o haloalkanes
 Aldehyde enolates may undergo aldol condensation
 Ketones may undergo polyalkylation
 Ketones may produce regioisomeric products
 Ideal alkylation conditions
 May form a highly nucleophilic resonance structure
General Mechanism
Aldol Addition
Aldol Dehydration
Aldol Condensation of Ketones
Crossed Aldol Condensation
Intramolecular Aldol Condensation
 aldehyde → aldehyde alcohol → α,β-unsaturated aldehyde

 Aldol Addition: (1) Enolate generation, (2) Nucleophilic attack, (3)

Protonation
 50-60% yield and does NOT react further when carried out at >5oC
 Aldol Dehydration: (1) Deprotonation, (2) Dehydroxylation
H O H O O

H H

H
H C
O CH C C H

H H

H
 H O O

H H

H C C C C H

H H

H O H
 Give the structure of the (1) hydroxyaldehyde product of aldol
condensation at 5oC and (2) of the α,β-unsaturated product of
each of the following aldehydes:
a) Propanal
b)Butanal
c) 2-phenylacetaldehyde
d)3-phenylpropanal

 Can benzaldehyde undergo aldol condensation? Why or why

not?
 Bruice, P. (2005). Organic Chemistry (4th ed.). Prentice-Hall.
 Hornback, J. M. (2006). Organic Chemistry (2nd ed.). Belmont, CA:
Thomson Learning, Inc.
 McMurry, J. (2011). Organic Chemistry with Biological
Applications (2nd ed.). Belmont, CA: Brooks/Cole, Cengage
Learning
 Vollhardt, K., & Schore, N. (2011). Organic Chemistry: Structure
and Function (6th ed.). USA: W. H. Freeman and Company.
