CHEM 332. Spring 2014
Problem Set 5
Prof Donald Watson
1. Please rationalize the following observations
1
(a) In the room temperature H NMR spectrum of N,N – dimethylformamide (DMF), two
methyl signals are observed. As the temperature is raised they merge into a single signal.
(b) Analysis of the IR stretching frequencies showed that N-Methylacetamide absorbs at
-1
-1
much lower frequency (1688cm ) than methyl acetate (1750 cm )
(c) Peroxyacetic acid (pKa=8.2) is much weaker acid than acetic acid (pKa = 4.74).
(d) 4-Methoxybenzoic acid is a weaker acid than benzoic acid, but methoxyacetic acid is a
stronger acid than acetic acid.
(e) Phenyl acetate is more reactive towards basic hydrolysis than methyl acetate.
2. A catalytic amount of sulfuric acid was added to a mixture of 1 mole of acetic acid and 1 mole
18
of special methanol containing the heavy O isotope of oxygen. After a short period, the acid
was neutralized to stop the reaction, and the components of the mixture were separated.
O
Me
O
cat. H 2SO 4
18
H 3C O H
OH
Me
O
Me
H 2O
(a) Propose a mechanism for this reaction
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(b) Follow the labeled O through your mechanism, and show where it will be found in the
products.
3.
Thioesters (2) are more reactive than esters (1) towards nucleophilic acyl substitution.
Explain you reasoning.
O
O
Me
O
Me
Me
(I)
S
Me
(2)
4. List the following esters in order of decreasing reactivity towards basic hydrolysis.
O
O
Me
O
O 2N
Me
O
O
Me
O
MeO
5. Please draw a arrow-pushing mechanism for the following Dieckmann condensation.
O
Me
O
1. NaOMe/MeOH
2. HCl
O
O
Me
O
O
O
Me
6. Predict the product with mechanism.
O
SOCl2
OH
Me
Me
OH
Me
cat. H 2SO 4
OH
Me
O
excess
H 2O
N
cat. H 2SO 4
Me
1. Mg
2. CO2
3. H 3O+
Br
O
1. NaOH, H 2O
H2
Me
2.H 3O+
O
O
Me
O
1. Diethyl ether, 20 °C
2. H +, H 2O
EtMgBr
(excess)
Et
1. DIBAL, toluene -60 °C
2. H +, H 2O
O
O
Me
1. NaOMe/MeOH
2. HCl
O
Me
O
Me
7. Propose a synthesis for each of the flowing compounds, using a Robinson annulation
(Check this reaction in PS4 question # 9)
O
Me
O
Me
8. How Claisen condensation can be used to synthesize 4-methyl-3-heptanone from methyl
propanoate?
O
Me
O
Me
Me
Me
Me
O
9. Amide formation from carboxylic acid can be carried out under mild condition using DCC
(Dicyclohexylcarbodiimide). It promotes amide formation by reacting with the carboxyl group
of an acid and activating it toward nucleophilic addition-elimination. Please draw an arrowpushing mechanism for the following reaction.
N C N
O
Me
OH
Me
H
N
O
DCC
NH 2
Me
N
H
Me
H
N
O
N,N-Dicyclohexylurea
10. Draw an arrow-pushing mechanism for the following base-induced transesterification.
O
Me
O
Me
EtOH
(Excess)
O
NaOEt
Me
O
Et
MeOH