Organic Chemistry I (230-001)
Examination III
November 24, 2004
KEY
Name (PRINT LEGIBLY):
Please provide clear and concise answers to all of the
following questions. Use equations and/or drawings to
support your answers where appropriate.
Please answer questions in the area provided, the back of an
exam page or on the clearly labeled spare page.
Problem
1. (a-c)
2. (a-f)
3. (a-b)
4.
5.
6. (a-e)
Score
/12
/30
/10
/14
/14
/20
Total
/100
PLEASE OBSERVE THE FOLLOWING.
1) Write LARGE and LEGIBLY. If I can’t read what you write,
I can’t give you full or partial credit.
2) Read each question carefully before answering. If you
don’t answer the question I posed, you will not receive
credit.
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1. (4 pts each, 12 pts)
(a) Arrange the compounds (1-3) below in order of increasing
acidity for the indicated hydrogen. Briefly explain your reasoning.
O
O
O
EtO
O
O
O
OEt
OEt
H
H
H
1
2
3
:
pka
13
9
11
Thus, acidity increases in the order: 1 < 3 < 2.
1 and 3 have important resonance structures involving the
carboxylate oxygen contributing to their ground state structure
(shown for 3 below; note that contribution of such structure is
increased for 1). This stabilization of 1 and 3 means that it is more
difficult to form their conjugate-base by proton loss; and thus they
are less acidic
O
O: O
O
:
: :
+
OEt
:
OEt
H
H
Thus, ground state resonance effects dominate (electronwithdrawing) inductive effects in this case.
(b) Circle the more acidic of the pair of compounds below, and
provide a short reason for your answer.
H
H
H
O
H
O
because of resonance stabilization of conjugate base
2
(c) Which of the following lists the compounds in order of
decreasing acidity? Circle your answer.
a. H2O > HC≡CH > NH3 > CH3CH3
b. HC≡CH > H2O > NH3 > CH3CH3
c. CH3CH3 > HC≡CH > NH3 > H2O
d. NH3 > H2O > CH3CH3 > HC≡CH
e. H2O > NH3 > HC≡CH > CH3CH3
2. (5 pts. each, 30 pts. total) Draw the major product of each of the
following reactions. If no reaction is expected to occur, write “No
reaction.” Be sure to indicate the stereochemistry of the product, if
appropriate. A mixture of configurations should be indicated with a
squiggly bond (
) to one of the groups attached to the
stereogenic C atom.
(a)
H Br
H3C(H2C) 3C
C
H 3C
CH3
H
-
C: Na
+
C
CH3
C
H2
C
H 3C
H
E-isomer
(Hint: consider the pKa of HC≡CH)
The pKa of HC≡CH ~ 25 and thus, acetylide ions are strong bases
as well as good nucleophiles.
When secondary alkyl centers react with good bases, whether they
are good or poor nucleophiles, E2 elimination occurs. The E-isomer
predominates in accord with Zaitsev’s rule.
(b)
OH
+ NaI
NO REACTION
H2O/ acetone
Hydroxide ion (-OH) is a poor leaving group
3
(c)
OTs
CH3COOH
(H3C) 3C
CH3
(H3C) 3C
H
CH3
H
O2CCH 3
Acetic acid is protic and nucleophilic. Secondary alkyl centers
undergo SN1 substitution when there is a very high concentration of
nucleophile.
(d)
HCl
Br
NO REACTION
25 ˚C
Primary alkyl halides are not electrophiles under acidic conditions.
The carbocation required for either the SN1 or the E1 mechanism is
not sufficiently low in energy to be formed, so neither SN1 nor E1
will proceed.
While SN2 mechanism is possible under acidic conditions, a good
nucleophile that is also a poor base is required, as well as much
more harsh conditions than above.
(e)
CH3CH 2O -Na+
Br
H 3C
CH3CH 2OH
H 3C
E - ISOMER
Tertiary alkyl centers are so hindered that they never undergo SN2
substitution. E2 elimination occurs with these substrates under
basic conditions. In accord with Zaitsev’s rule, the E-isomer
predominates.
4
(f)
CH3COO -Na +
CH3
CH3
DMF
H
OTs
H
R - configuration
O2CCH 3
S - configuration
Secondary alkyl centers undergo SN2 substitution with good
nucleophiles that are also poor bases. Inversion of stereochemical
configuration at the electrophilic carbon always accompanies SN2
reaction.
3. (a, 5 pts) Rank molecules A-E (below) according to how fast they
undergo E2 reaction mechanism:
Br
Br
Br
B
A
C
D
Br
Br
E
Oops, ignore A since A and C is the same.
SLOWEST:
E <B
< C <
D
FASTEST
(b, 5 pts) For either the fastest or the slowest molecule to
undergo E2 reaction mechanism, give a brief explanation for your
answer above.
Br
D
H
Only the antiperiplanar H-C-C-Br undergoes
E2. So we need Br in the axial position to
do antielimination
ring flip
H
H
Br
Not much of the comformer containing
axial Br is in the equilibrium mix
due to high energy. But more is present
for C than B due to fewer CH 3 groups
and hence fewer destabilizing
interactions
Br
Br
H
Br
H
ring flip
B
ring flip
E
C
Br
E does not have an antiperiplanar
H to eliminate!
Br
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4. (14 pts) Which alkyl halide and what conditions should be used to
prepare the following alkene in good yield by E2 elimination reaction
mechanism?
Briefly explain reasoning. No credit will be given
without a valid explanation.
CH2
CH2
CH2 Br
K+ -OC(CH 3)3
HOC(CH3)3
Using the above primary alkyl halide as starting material, the
desired compound is the only possible product of β-H elimination.
Using a strong and bulky base such as t-butoxide minimizes SN2
reaction of the primary alkyl halide! (see homework problems for
more)
5. (14 pts) Ethers can be prepared by SN2 reaction of alkoxide ions
with alkyl halides. Which of the two possible routes shown below
would you advise Joe Greenhorn to use to prepare cyclohexyl methyl
ether in high yield? Briefly explain your reasoning. No credit will be
given without a valid explanation.
: :
O: -
(A)
+ CH3I
OCH3
or
I
:
(B)
:
CH3—O: - +
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Route A will produce cyclohexyl methyl ether in high yield B because
SN2 substitution is fast for methyl halides under basic conditions.
Also, this route removes E2 elimination as a competing reaction
since CH3I contains no β-hydrogens!
Route B will lead to a mixture of substitution and elimination
products since CH3O- is both a good nucleophile and a good base,
and the reaction involves a secondary (hence hindered) alkyl halide!
In fact, E2 elimination will dominate when a secondary alkyl center
reacts with a good base, whether it is a good or poor nucleophile.
6. (20 pts) Answer the following question in reference to the reaction
energy diagrams below. The labeled points on the reaction energy
diagrams are either energies or chemical species, depending on the
sentence.
a. __C___ might be a catalytic intermediate or even a carbocation.
b. The energy difference between _F and G_ might determine the rate
of an SN2 reaction.
c. The energy difference between __A and E__ might determine the
ratio of product to starting material of an E1 reaction.
d. The Hammond postulate states that D is most similar in structure to
___C___.
e. Factors that destabilize ___G___ will decrease the rate of an E2
reaction.
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