Aldehydes and ketones can exist in the keto

Aldehydes and ketones can exist in the keto
or enol tautomers. The keto form is
predominant unless some stabilizing factor
for the enol is present.
An isolated C=O bond is usually 2-3
kcal/mole more stable than an isolated C=C
bond.
O
H3C
OH
CH3
H3C
CH2
keto
tautomer
enol
tautomer
>99.99%
0.00025%
The tiny amount of enol present makes the
monobromination of acetone possible under
acidic conditions.
O
O
Br2, CH3COOH
H3C
CH3
H3C
H
OH
+
H3C
CH2
CH2Br
O
Br–Br
H3C
+ Br
CH2Br
Aldehydes and ketones have only trace
amounts of enol tautomer in solution, but
1,3-diketones (!-diketones) exist with
significant amounts of the enol tautomer
present. Why?
O
H
O
OH
99.99%
0.01%
OH
CH3
H
99.95%
CH2
0.05%
O
O
20%
O
H
O
80%
The conjugation of the C=C and C=O bonds
stabilizes the molecule and the hydroxy
group can hydrogen-bond with the keto
oxygen atom.
O
H
O
Why do phenols exist predominantly in the
enol form?
OH
enol
tautomer
O
keto
tautomer
Two of DNA’s four nitrogen-containing
bases, guanine (G) and thymine (T) exist
mainly as their keto tautomer at
physiological pH. This allows for hydrogen
bonding with their complementary bases
cytosine (C) and adenine (A), the basis of
DNA’s double helical structure.
O
H
O
OH
CH3
N
N
H
thymine
CH3
N
O
N
H
OH
O
H
H2N
N
N
N
N
H
guanine
N
N
H2N
N
N
H
Expt. 47 – Synthesis of Dimedone and
Measurements of the Tautomeric
Equilibrium Constant
The goal of this experiment is synthesize
dimedone (a 1,3-diketone) and measure its
keto:enol ratio by NMR.
O
O
Me
Me
Keto
O
OH
Me
Me
Enol
Will the enol form of dimedone be able to
form an intramolecular hydrogen bond
between the hydroxy group and the keto
oxygen atom?
O
O
Me
Me
Keto
O
OH
Me
Me
Enol
Dimedone’s enol tautomer will be stabilized
only by conjugation of the double bond with
the carbonyl group.
How would the appearance of the keto and
enol tautomers differ in the NMR spectrum
of dimedone?
How can the NMR spectrum of dimedone be
used to calculate the enol:keto ratio?
Keq = 2 x integrated area of the H–C=C
integrated area of the H2C(C=O)2
Simulated NMR spectrum of dimedone s keto
tautomer
O
2.37
0.99
0.99
3.61
2.37
O
4
3
2
PPM
1
0
Simulated NMR spectrum of dimedone s enol
tautomer
16.77
HO
1.88
0.99
0.99
2.25
6.94 H
O
18
16
14
12
10
PPM
8
6
4
2
0
The synthesis of dimedone starts with the
reaction of dimethyl malonate with 4methyl-3-penten-2-one (mesityl oxide)
under basic conditions.
O
MeO
O
C
H2
pKa = 13
OMe
O
NaOCH3
CH3OH
MeO
O
C
H
OMe
O
MeO
O
C
H2
OMe
O
NaOCH3
CH3OH
MeO
O
C
H
OMe
pKa = 13
O
O
4-methyl-3-penten-2-one
(mesityl oxide)
CH3
COOMe
COOMe
Me
Me
O
CH3
COOMe
MeOH
O
CH3
COOMe
COOMe
Me
Me
COOMe
Me
Me
The addition of the dimethyl malonate
enolate to mesityl oxide is an example of
what type of reaction?
After the Michael addition of dimethyl
malonate to mesityl oxide takes place, an
intramolecular aldol condensation occurs.
O
CH3
COOMe
OMe
O
CH2 OMe
O
COOMe
Me
Me
COOMe
Me
Me
O
CH2 OMe
OMe
O
O
O
COOMe
Me
COOMe
Me
Me
O
O
+ OMe
COOMe
Me
Me
This is an example of a Robinson
annulation.
Me
O
O
OMe
Me
heat
Me
1) NaOH
2) H3O+
O
O
O
Me
O
O
O
Me
Me O
O
H
O
H
OH
CO2 +
Me O
Me
Me
O
O
Me
Me
NMR and IR spectra of mesityl oxide
Physical Properties of Reactants and Products
Safety Information on Reactants and Solvents
Dimedone Synthesis:
Add 25.0 mmol of dimethyl malonate and a
stir bar to a round-bottom flask (keep in
mind that you don’t want the flask to be
more than one-third full with everything
added).
Add 6.0 mL of a 25% solution of sodium
methoxide in methanol to the dimethyl
malonate.
Attach a condenser and reflux gently until
everything (or nearly everything) dissolves.
Make sure the solution is stirring.
After allowing the solution to cool, add the
mesityl oxide through the condenser in
several small portions. Attach a drying tube
to the condenser and reflux for one hour
with stirring.
If you need to recrystallize your trityl
alcohol from expt. 30 or form the
carbocation, now is a good time to do it.
After the one hour, remove the condenser
and allow the methanol to evaporate until
the liquid has disappeared, but the residue is
still moist (do not let the residue cake onto
the flask).
Add 20 mL of 3.0M sodium hydroxide and
reattach the condenser to reflux for another
hour.
Add 15 mL of 6.0M HCl to a 125-mL
Erlenmeyer flask and add the warm reaction
solution after the one hour ester hydrolysis.
Place a watch glass over the mouth of the
flask and boil gently with stirring on a hot
plate. Add more water as necessary. Heat
10-15 minutes until you no longer see the
evolution of carbon dioxide.
Allow the reaction mixture to cool to room
temperature and then cool further in an ice
bath to complete the crystallization of the
dimedone.
Collect the product by vacuum filtration and
let it air-dry.
Recrystallize (can be done the following
week) with 1:1 acetone:water. Remember to
use a minimal amount of solvent to
recrystallize.
After collecting the recrystallized product by
filtration, dry, weigh and measure its
melting point.
Lastly, record the NMR spectrum of the
purified dimedone in CDCl3.