1. Consider the following solvents. For each, draw the structure and circle the appropriate
solvent classification.
a) isopropanol
Structure:
d) Acetone
Classification:
(Circle one answer)
Structure:
polar, protic
Classification:
(Circle one answer)
polar, protic
OH
O
polar, aprotic
polar, aprotic
nonpolar, aprotic
nonpolar, aprotic
b) DMF
e) THF
Structure:
Classification:
(Circle one answer)
Structure:
polar, protic
polar, protic
O
H
N
O
polar, aprotic
polar, aprotic
nonpolar, aprotic
nonpolar, aprotic
f) water
c) HMPA
Structure:
Classification:
(Circle one answer)
Classification:
(Circle one answer)
Structure:
Classification:
(Circle one answer)
polar, protic
polar, protic
O
Me2N
P
NMe2
NMe2
polar, aprotic
nonpolar, aprotic
H
O
H
polar, aprotic
nonpolar, aprotic
NKG 4/19/10
2. For each compound shown below indicate whether the compound is nucleophilic or
electrophilic at the marked atom (*).
a)
c)
e)
O
*
*
OTs
Me
electrophilic
O S O
electrophilic
*
d)
b)
electrophilic
* nucleophilic
H2O
N
*
N
nucleophilic
3. Consider the following elimination reactions. For each:
a) draw the major product
b) determine if the elimination proceeds by E2 or E1 (circle your answer)
Br
NaOEt
EtOH
OTs
E1 or E2
MeOH, heat
E1 or E2
OH
cat. H2SO4
benzene, heat
Br
E1 or E2
t-BuO–K+
t-BuOH
E1 or E2
NKG 4/19/10
4. Consider the following substitution reactions. For each:
a) draw the major product(s) that arise from substitution
b) determine if the given substitution takes place by SN2 or SN1 (circle your answer)
EtONa
OEt
Br
SN1 or SN2
DMSO
NaI
I
Cl
acetone
I
SN1 or SN2
OH
H2O
SN1 or SN2
Br
OMe
OMe
+
MeOH
SN1 or SN2
5.
a) Which of the following two substrates would likely undergo faster E2 elimination (circle your
answer)?
H
H
Br
Br
or
H
H
A
B
b) Provide an explanation for your answer that includes 3-dimensional drawings.
H
H
Br
H
H
A
H
H
H
Br
E2 requires antiperiplanar relationship
between breaking C–H and C–Br bonds.
This is possible in substrate A,
but not in substrate B.
B
NKG 4/19/10
6. Rank the following in order of nucleophilicity (1 being most nucleophilic, 4 being the least
nucleophilic).
CH3MgBr
EtOH
EtO–
t-BuOH
1
3
2
4
7. Based on your knowledge of pKa values, rank the following in order of leaving group ability
(1 being the best leaving group, 4 being the worst leaving group).
Br –
–CN
TsO–
1
2
–CH
3
4
3
8. Draw a reaction coordinate diagram for the following reaction. Be sure to label starting
material(s), transition state(s), product(s), activation energy(ies), and intermediate(s) (if
applicable).
Cl
N3
NaN3
acetone
(Generic SN2 reaction coordinate diagram)
transition state
R
N3
C
Cl
H Me
Energy
EA
substrate
+ nucleophile
product + LG
reaction progress
NKG 4/19/10
9. Provide reaction conditions for the following transformation (place your answers above and
below the reaction arrows).
OH
O
Br
NaBH4
1. TsCl, pyr
EtOH
2. NaBr, DMF
10. Provide a synthetic scheme for the following conversion.
Cl
N3
Cl
Br
NaBr
acetone
NaOH
HMPA
OH
N3
NaN3
DMF
TsCl
NaN3
DMF
OTs
pyridine
11. Amanda has performed a retrosynthetic analysis on Compound F. After performing several
disconnections, she arrived at bromobenzene and acetaldehyde (shown below). Provide a
forward synthesis of Compound F that relies on Amanda’s strategy.
OH
Me
Br
Me
O
+
H
Me
F
O
OH
Br
1. Mg
2. acetaldehyde
(with aqueous workup)
Me
H
PCC
OH
Me
H3CMgBr
Me
(with aq. workup)
Me
F
NKG 4/19/10
12. Grace has performed a retrosynthetic analysis on Compound A. After performing several
disconnections, she arrived at allyl bromide and carbon dioxide (shown below). Provide a
forward synthesis of Compound A that relies on Grace’s strategy.
O
Br
O
+
CO2
A
Li
Br
O
CO2
Li
O
H+ workup
O–Li+
OH
Br
1. NaH
2.
O
Br
O
A
13. Draw an arrow-pushing mechanism for the following transformation.
O
NaBH4
OH
EtOH
H
Na
H B H
O
H–OEt
H
H
NKG 4/19/10
14. Draw an arrow-pushing mechanism for the following solvolysis experiment.
I
OEt
EtOH
Et-O-H
H
Et-O-H
O Et
15. Draw an arrow-pushing mechanism for the following elimination reaction.
Br
MeOH, heat
Me-O-H
H
NKG 4/19/10