ORGANIC CHEMISTRY
CH 399, Spring 2003
WORKSHOP 1
Carbonyl Compounds: Nucleophilic Addition
1. a. Discuss the similarities and differences in the structures and reactivities of the double
bonds of 2-methylpropene and 2-propanone.
b. With part a in mind, account for the following observations. Identify the nucleophile and
the electrophile for the first step of each reaction.
O
H 3C
HO
CN
HCN
C
CH3
CN
C
H 3C
(fast)
CH3
CH2
CN
HCN
C
H 3C
CH3
No Reaction
CH2
HCl
in ether
C
H 3C
CH3
(CH3)3 C–Cl
2. Write detailed electron-pushing mechanisms that account for the stated observations.
a. The following reaction occurs rapidly at pH = 5 (weakly acidic) but fails at pH = 1
(acidic).
H3C
O
C
CH3
NH NH2
+
H3C
N
C
NH
+
H2O
CH3
b. Acetone can be labeled with 18O (= O*) by reaction with labeled water. The labeling is
catalyzed by both acid and base.
H3C
O
C
H3O* or
+
CH3
H2O*
(excess)
HO*
H3C
O*
C
+
CH3
H2O
3.
When 2,2-dimethoxypropane is mixed with butanol and a catalytic amount of
p-toluenesulfonic acid in benzene, the equilibrium shown below is rapidly established.
The lowest boiling component of this mixture is methanol. Provide a reasonable
mechanism for the reaction and suggest an experimental technique that could be used to
shift the equilibrium to the right and thus make the reaction useful for synthesizing the
dibutylketal. (Note: There is no water present. Therefore, the reaction does NOT proceed
by hydrolysis of the ketal to acetone.)
OCH3
+ 2
O
p-TsOH
OH
OCH3
+ 2 CH 3OH
O
benzene solvent
What features of the reaction mechanism account for the fact that this reaction occurs
rapidly under mild conditions?
4.
Give a reasonable mechanism for each of the following reactions. Use correct electron
pushing.
OCH3
N
Ph
dry HCl
+ CH3OH
(excess)
OCH3
+ PhNH3 Cl
O
1. Ph3P
BrCH2CH2 CH2CH2
2. Me3COK
5.
The pinacol rearrangement is a reaction that produces a carbonyl compound from a
vicinal diol. Give a mechanism for the example below. Inspect the rearrangement step in
your mechanism, and rationalize why the rearrangement should be a favorable process.
CH3
CH3 CH3
C C CH3
+
H3O
CH3
OH OH
pinacol
O
C
CH3
C CH3
+
H2O
CH3
pinacolone
The following related reaction gives only one product as shown.
H
C
H
C CH3
+
H3O
CH2
O
C CH3
+
H2O
OH OH
What are the other two possible products? Account for the observed selectivity.