Summary Sheet 2: Enols and Enolates

Name

Structure

pKA* of
H

Example

O
H

H3C

O
ketone

R'

H3C
O

OR

H3C

amide

O
NR2

H2C

NH2 = 1 amide
NHR = 2 amide
NR1R2 = 3 amide
O
lactam
(cyclic
amide)

)n

C
H2

O
OH

H3C

R
O

anhydride

nitrile

Note 1

OH
O

*
H3C

Cl
O
O

RCN

Note 2

Cl
O

*
R H3C

CH3

Tautomerism: a form of isomerism where

a keto converts to an enol through the movement of
a proton and shifting of bonding electrons

O
O

Note 2
Me

Me-CN

Note 2: It is difficult to measure the pKa of

these species due to their reactivity.
*source: P. Y. Bruice, "Organic Chemistry"
Note that some of of these values differ slightly from
textbook to textbook and instructor to instructor.
However, there is universal agreement that for
a given structure, pKas increase in the order
aldehyde < ketone < ester < amide
If you have a vastlyl different set of values I
would appreciate it if you brought it to my attention.
For a comprehensive list of pKa values see:
1)evans.harvard.edu/pdf/evans_pKa_table.pdf
2) www.chem.wisc.edu/areas/reich/pkatable/

H
H

> OH > OR, NHAc > CH3, R > Cl, Br, F, I > C(O)OR
CF3, etc.

Substitution of the -carbon by a second carbonyl

derivative makes the -proton even more acidic:

Me

Me

Me
24 : 76 (at 23 C)

Me

Me Me

pKa = 9

pKa = 11

H X

t-Bu

O
Et2N

forms readily!

O
NR2 >

O
OR >

O
Me >

O
>

CF3

RO

O
OR

increasing reactivity toward nucleophilic attack

increasing stability of enolate
Can predict the course of the reaction by pKa!

Key Reaction: Enolate Formation

Enolate = deprotonated enol
i-Pr

O
H3C

OEt

i-Pr
N
Li (LDA)

O Li
H

(or other
strong base)
Carbonyl compound

OEt

H
ester enolate
O-bound form

Important: the Enolate is a NUCLEOPHILE

Amphiphilic =nucleophilic at both O and C;
here we focus on the reactions at C.

OMe MeO

t-Bu

Et2N

OMe

Two key examples:

O

O M

pKa = 13

OEt
The rate of keto/enol interconversion isgreatly enhanced by acid:
Acid makes carbonyl more electrophilic, increasing acidity of protons, facilitating formation of enol: this increases K1

4. . Conjugation is stabilizing.

O
OH

Me

Li

OEt
H
C-bound form

note: though an ester enolate

is shown here, the reaction of
any enolate with an aldehyde
is generally called an "Aldol".

OH O
H

OEt

Aldol reaction

Me

3. Strongly hydrogen bonding solvents can disrupt

this, however. The above equilibrium is 81:19
using water as solvent.

does not form

NEt2

Enolate
(oxy-anion resonance form)

The aromatic electrophilic substitution chart is a good proxy

for the ability of a functional group to donate to a carbonyl:

2. Hydrogen bonding stabilizes the enol form.

H-bond
H
O
O
O
O

t-Bu LiNEt
2

least acidic

CH3

The reactivity of the alkene toward nucleophilic attack is directly related

to the stability of the enolate that forms -

OMe
CH3

most acidic

Exclusive

NEt2
Li

Answer: The more electron-poor the carbonyl, the greater will

be its ability to stabilize negative charge. Conversely, the
greater the donating ability of a substitutent on the carbonyl,
the less it will be able to stabilize negative charge.

NR2 , O

CH2

enolate: stabilized!

Question: How do you explain the relative acidity of the

following series?
O
O
O
O
>
>
>
H3C
NR2
H3C
CF3
H3C
CH3
H3C
OR

25

Note 1: The carboxylic acid is deprotonated

first. Subsequent deprotonation of the -carbon
would form a dianion, which has a high
activation barrier due to charge repulsion. It
can be done, but it requires a very strong base.

CH3

Enolate
(Carbanion resonance form)

Five factors that influence the relative

proportion of keto/enol:
1. Aromaticity
O
OH

Not observed

Acetone in D2O will slowly incorporate deuterium at the

carbon. The enol form is responsible for this behavior.
The rate of keto/enol tautomerism is greatly increased by
acid (see below right)

LiNEt2

highly unstable

M
Conjugate base (enolate)
25
~10 more acidic just by
replacing H with a carbonyl!

OMe
CH3

Why the huge difference in acidity? The lone pair is

stabilized by donation into the carbonyl system.

enol form

OMe

The enol tautomer is most significant for ketones and

aldehydes. (You may also encounter it with acid chlorides in
the mechanism of the Hell-Vollhard-Zolinsky reaction). Esters
and amides are less acidic and exist almost exclusively as the
keto form (e.g. >106 : 1 keto: enol for ethyl acetate)

N Me

O
acid
chloride

Likewise, the presence of a carbonyl group activates alkenes toward

nucleophilic attack:

H2C CH3

Methyl propionate
pKa = ~25

For acetone (R=CH3) the keto:enol ratio is ~6600:1 at 23

C. Main reason is the difference in bond strengths between
the two species.

O
carboxylic
R
acid

30

NMe2

NH(R)H C
2

Conjugate base

OMe

OH

keto form
O

Ethane
pKa = ~50

Key Concept: Tautomerism

O

H2C

)n

H3C CH3

OMe

Effect on reactivity of alkenes:

The carbonyl is an electron withdrawing system with

low-lying * orbitals. It stabilizes adjacent negative charge.

25
O
O
(

20

Me

O
lactone
(cyclic
ester)

O
ester

Effects on acidity of alkyl groups

Carbon, oxygen: sp2 hybridized

OCC bond angle ~120
C=O bond strongly polarized
toward oxygen.
Carbonyl carbon is partially positive
therefore electrophilic!
Lone pairs render oxygen weakly
nucleophilic (will react with strong acid)

17

aldehyde
R

Structural Features of the Carbonyl Group:

Me
Preferred enol form

5. As with alkenes, increasing substitution increases

thermodynamic stability (assuming equal steric factors)

H X
R

H H
Keto

K1
R

H H
X:

K2

H O
R

H X

H
Enol

Enol is nucleophilic at -carbon, acid is

excellent electrophile: this increases K2

Net result: Addition of acid speeds proton

exchange between the keto and enol forms.

O M
OEt

OH O
OR

Claisen Condensation
OEt

The goal here is clarity and consistency. I

would greatly appreciate feedback on any
errors, omissions, or suggestions for
improvements. Thanks!

version 1.0, 4/13/10

copyright James Ashenhurst, 2010.
suggestions/questions/comments?
james@writechem.com
masterorganicchemistry.wordpress.com