140A CHEM 2nd Midterm Review Problem Set
Chapter 4: Cylcoalkanes
1. Draw all possible conformers of (trans)-1-bromo-3-chlorocyclohexane in chair form.
Indicate the most stable conformer. Hint: There are four possible conformers
2. The Wurtz Coupling is one of the oldest organic reactions, and produces the simple
dimer derived from two equivalents of alkyl halide. The intramolecular version of the
reaction has also found application in the preparation of strained ring compounds. Draw
a reasonable arrow pushing mechanism for this reaction.
Br
2 Na
Br
Challenge question: 1,2-diaminecyclohexane is more stable when both substituents are in
equatorial position yet 1,3-diaminecyclohexane is more stable when both substituents are in
axial position. Why is this? Explain. Hint: Remember the strongest of intermolecular forces you
saw in General Chemistry. These can apply intramolecularly as well.
NH2
NH2
NH2
NH2
1,2-diaminecyclohexane
1,3-diaminecyclohexane
Chapter 5: Stereochemistry
1. Penicillin is a -lactam antibiotics and has been used in the treatment of bacterial
infections. Circle all stereocenters in Penicillin and assign absolute stereochemistry (R or
S) to each.
H
N
O
S
N
O
OH
O
2. Taxol, shown below, is a natural anti-cancer agent found in the bark of the Pacific Yew
tree Taxus Brevifolia. Circle all asymmetric C centers and indicate how many
streoisomers are possible. Assign absolute stereochemistry to the all carbons indicated
by an arrow.
O
O
O
O
NH
OH
O
O
H
OH O O
O
OH
O
O
3. Determine the stereochemical relationship (enantiomers, diastereomers or identical)
between the following pairs of molecules:
OH
H
a)
_________________________
CH3
CH3
H
CH3
b)
_________________________
H
H
H
OH
CH3
H
H 3C
CH3
OH
OH
H Br
c)
H 3C
CH3
Br H
__________________________
H CH3
H3C H
Challenge Question: Recently a research group in Germany published (Angew. Chem. Int. Ed.
2009, 48, 9105 9108) their synthetic efforts towards Englerin A, a natural product known to be
a powerful anti-cancer agent. Upon completion of the molecule they measured the optical
rotation and obtained the exact opposite value of the natural product. For this reason, the
concluded had they made the wrong unnatural enantiomer of Englerin A (shown below). Draw
the correct natural enantiomer of Englerin A.
O
O
O
O
O
H
OH
Me
Me
H
Chapter 6: Properties and Reactions of Haloalkanes
1. Name the following substrate molecule. Predict the product(s) of the reaction of this
compound with NaOCH3 and show a reasonable arrow pushing mechanism that
explains the formation of this product. Make sure to show stereochemistry if
necessary.
CH3
Br
2. For the following reaction: predict the product for each reaction .and draw the
structures of all solvents. Show stereochemistry if it applies. Write N.R. for no
reaction.
O CH3
F
NaN3 (1 equiv.)
HMPA
Br
O
O
S
O
CF3
NaCN
DM F
NaSCN (1 equiv)
Br
DMSO
Br
H3C
Br
Na I
acetone
CH3
CH2Br
KF, 18-crown-6
CH3CN
3. Put in decreasing order (highest to lowest) of nucleophilicity:
O
SeCH3
OCCH3
SCH3CH2
H2O
OCH3
A
B
C
D
E
_________ > _________ > _________ > _________ > _________
Challenge Question: A graduate student set-up the following reaction in lab hoping to achieve
elimination of the bromine and formation of an alkene (E2 reaction, look ahead in Chapter 7 for
this reaction). Even so, he did not get the product he predicted below. Using analytical methods,
he determined that the bromine atom he wanted to eliminate was no longer present in his
product yet no double bond was formed. Predict the product of this reaction, show an arrow
pushing mechanism that explains its formation. Hint: Remember that acid-base reactions are
faster the E2 or SN2
Br
H3C
NaOCH3
H3C
Br
CH3OH
Br
HO
HO
Challenge Mechanism.
A graduate student is testing a radical oxidation reaction in the lab in her work
with cluvenone, an anti-cancer and anti-fungal agent. In her attempts to
isolate the 1o alcohol (product A), she realizes that she is also forming the 2o
alcohol (product B). Furthermore, she realized that she obtains more of B than
A. Draw an arrow pushing mechanism for this transformation and explain why
product B is favored over product A. Also, explain which of the two radical
species formed in the initiation step is more stable.
HO
O
O
O
O OH
O
O
O
O
OH
O
O
O
OH
O
cluvenone
O
A
25%
B
75%