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Chemistry 215
Second Examination
March 17th , 2015
1.5 hours; 120 points
15
Signature ________________________________
ID No. ________________________________
he
21
Instructors:
Dr. Meg Breen
Professor Anna Mapp
Professor Corey Stephenson
Prob
Pts
Score
GSI
28
\____/
_____
II
25
\____/
_____
III
20
\_____/ _____
IV
29
\_____/ _____
18
\_____/ _____
Total
120
\_____/ _____
Complete structures are required unless you are given other specific instructions. Bond-line notation is acceptable
unless otherwise specified. Do not forget to include important features such as nonbonding electron pairs and non-zero
formal charges unless explicitly excluded. Precision in drawing counts. Check all three-dimensional representations to
ensure you are implying an unequivocal direction of bonding. Individual point values are given in the corner of each
answer space. Include specific chemical formula or drawing for reagents.
The exam has 7 pages total. A pKa/information table is on the last page.
Name _____________________________________
W.15.215
Exam No. 2
Page 1
I. (28 pts)
Complete the following reaction schemes as indicated. Be sure to show stereochemistry where appropriate.
A) J. Org. Chem. 2015, 80, 2397.
O
1)
O
K2CO3, heat
OCH2CH 3 2) H O+
3
workup
W
15
C15 H24O4
OCH2CH 3
several reaction
steps
Include stereochemistry
1)
21
5
1) 1 eq
Cl
Cl
O+ workup
OH
MgBr
2) H3
OCH2CH 3
2)
HO
he
Br
H 3C
MgBr
1)
1 eq
O
OCH3
4
Br
2) H3O+ workup
HO
Br
+ enantiomer
4
Name _____________________________________
W.15.215
Exam No. 2
Page 2
KOH
+ H2O
condensation product B
21
5
W
15
C11 H18 O2
cis-jasmone
molecule A
6
In addition to cis-jasmone there are three other potential aldol condensation products that could arise from
molecule A. They are consititutional isomers of cis-jasmone In the three boxes below, provide the structures
of each of the other potential aldol condensation products. Note: the order in which you draw the structures
does not matter.
condensation product C
condensation product D
Of the three structures you drew above (B, C and D), which is the closest in stability to cis-jasmone? Write
the letter corresponding to the structure:
2
Circle each of the statement(s) that is true:
he
Cis-jasmone is the most stable aldol condensation product that could be formed in the reaction.
Cis-jasmone is the least stable aldol condensation product that could be formed in the reaction.
B) From J. Med. Chem. 2015, 58, 1244-1253. Provide the structure of the product.
O
+
O
NaOH
H
HN
CH3CH2OH
4
Name _____________________________________
W.15.215
Exam No. 2
Page 3
A) Pyridine is generally considered a mild base, with the pKa of its conjugate acid measured as 5.
N
H
conjugate acid of pyridine
pKa = 5
N
pyridine
Cl
H 3C
W
15
Replacement of C-H bonds on the pyridine ring with other substituents can significantly alter the pKa of the
conjugate acid. In the case of the pyridine derivatives shown below, replacement of the C-H bond at position 2
in the ring leads to molecules with pKas of 6, 0.5, -0.44 and 7. Predict the pKa value that corresponds to each
substituted pyridine and write the value in the space below each structure.
H 2N
21
5
O
O
OCH3
he
Br
O
HO
4
+ 2 NaBr
Name _____________________________________
W.15.215
Exam No. 2
Page 4
O
+
molecule A
F 3C
1) 1.1 eq NaH
O
molecule B
heat
2) H 3O+
workup
O
+
F 3C
molecule C
O
molecule D
B: F 3C
B-H
F 3C
W
15
As you know, the initially formed intermediate, E, shown below, is deprotonated under the reaction conditions
(F, also shown). Under these reaction conditions, however, there is enough of molecule E to continue to
undergo productive reactions. In other words, you may ignore the formation of F in this reaction mechanism.
molecule F
molecule E
Provide a step-wise, curved arrow mechanism for the transformation of A and B to intermediate E (1st box)
and then for the formation of C & D (2 nd box). Use B:- as a generic base and B-H as the conjugate acid; use
H3O+ for the workup step. Make sure to use closed shell resonance structures.
21
5
O
H
molecule A
12
he
F 3C
O
molecule E
F 3C
molecule E
F 3C
O
molecule C
O
O
1 eq
HO
O
2
molecule D
12
O
O
OH
N
3
pKa
ACID
(Strongest Acid)
common carbohydrates
H N H
HO
O
HO S OH
9.4
H
OH
O H
O
Cl
O H
C
CH3CH2
CH3
OH
1.3
0.64
OH
3.2
CH3
17
19
Cl
25
C H
Cl
OH
H C C
H2
26
4.2
35
N H
4.6
36
he
H
O
C
CH3
OH
4.8
N H
C
HO
OH
H C N
CH3
H
H
6.5
9.1
H
C
H
H
CH3 9.2
44
O
C
43
H C H
41
5.2
- & -D -glucopyranose
H
H N
H3N
O
R
alanine: R = CH3
arginine: R = CH2CH2CH2 N
proline
15.7
Cl
OH
OH
15.0
CH3CH2
O
Cl3C
HO
HO
10.5
10.6
1.7
O
O
(Weakest Acid)
49
H OH O
H OH H OH
D -glucose
OH
H
O
CH3
HO H
D -ribose
10.2
N H
2.4
D -threose
-4.6
H
O
D -erythrose
HO
H
HO H
H OH H OH
CH3CH2
OCH3
CH3
HO
-7.2
CH3
10.2
OH
21
CH3
HO
H OH
HO
O
H
D -(+)-glyceraldehyde
O
HO
H OH
10.0
O
H
HO
HO
15
-12
H C N H
pKa
ACID
NH2
asparagine: R = CH2CONH2
aspartic acid: R = CH2CO2H
cysteine: R = CH2SH
glutamic acid: R = CH2CH2CO2H
glutamine: R = CH2CH2CONH2
glycine = R = H
H
histidine: R = CH2
N
N
Name _____________________________________
W.15.215
Exam No. 2
Page 5
V. (18 pts)
A) 2,6-Disubstituted tetrahydropyran ring systems in which the two substituents are cis to one another are
frequently observed in biologically active molecules. Recently Latif and co-workers described a
straightforward strategy for preparing cis disubstituted tetrahydropyrans (J. Org. Chem. 2015 DOI:
10.1021/acs.joc.5b00046). Provide the reagents and/or structures as necessary in the boxes provided.
OTs
OH
N(CH 3)2
O
O
H 3CO
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15
H 3CO
Li
21
5
An amine
An enol
Show stereochemistry
An enolate
Lithium diisopropylamide
N(CH 3)2
OH
he
MeO
B) Provide the reagents and/or structures as necessary in the boxes provided (J. Med. Chem. 2013, 56, 10142)
OMe
OMe
Show stereochemistry
O
MeO
Cl
OMe
1)
2) Molecule A
Molecule A
2
MeO
O
N
Ph