Problem set 6
Chapters 43, and 44.
1. Fill in the boxes with the reagents required to produce the stereoisomer shown, or with the MAJOR
stereoisomer produced by the reaction conditions given. For all structures, indicate whether the
structure is achiral, a single enantiomer, or racemic.
a)
O
watch the substitution pattern
Ph
O
H2SO4
O
Ph
achiral
b)
Bu S
Bu S
BuSH
Ph
Ph
Ph
O
Ph
O
O
H2N NH2
Ph
Ph
N NH
achiral
O achiral
soft Nu, soft electrophile
= conjugate addition
1,3-dicarbonyl to pyrazole
c)
O
1. H2N NH2
2. KMnO4
O
EtO
first the 6-membered ring forms with
only two double bonds, then is oxidized
to the aromatic product
O
EtO
O
N N
achiral
d)
HCl, H2O, ∆
Ph
O
P2S5
O
Ph
Ph
Ph
O
Ph
(±)
S
Ph
e)
POCl3
or
SOCl2
N
H
O
NH2
N
Cl
N
N
H
achiral
1
f)
O
Me NH2
O
MeO2C
OMe
MeO
O
N
CO2Me
HNO3, H2SO4
MeO2C
O
N
O2N
CO2Me
achiral
g)
NaN3,
NH4Cl
C N
Et3N
TsCl
H
N
N
N N
in situ generation
of HN3
use a weak base
appropriate for the job don't kill it with LDA
Ts
N
N
N N
h)
achiral
Ph
Ph
NaN3
Br
CuCl
Ph
N
N N
N
N
N
i)
achiral
NH
H
N
1 eq. Et3N
1 eq. BnBr
NH
Ph
tetrazole NH far more
acidic than pyrrole NH
N
N
N N
N
N N
j)
pyrrole is the most electron rich
ring, therefore the best at
electrophilic aromatic
bromination
achiral
1 eq. Br2
NH
NH
Br
N
N
2
2. Explain the regioselectivity of the reaction below using text and diagrams.
Cl
Cl
NaOMe
+ NaCl
N
N
Na+
Cl
–O
N
Cl
OMe
Cl
Me
Cl
+ NaCl
OMe
N
Cl
N
Cl
Na+
OMe
Anionic intermediate
stabilized by placement of
negative charge on
electronegative nitrogen atom
Cl
N
Cl
Na+
–O
Cl
Cl
OMe
Me
N
Cl
OMe
Cl
Cl
N
OMe
N
Cl
No resonance structure can be drawn with negative charge on nitrogen atom
3. a) Give the Lewis structure of phenyl azide (PhN3), showing all lone pairs, bonds orders, and charges.
N with 3 bonds, 1 lone pair =
total 5 e–, so it's neutral
Nitrogen normally has 5 valence electrons.
N with 2 bonds, 2 lone pairs =
total 6 e–, so negatively charged
Ph N N N
N with 4 bonds, no lone pairs
total 4 e–, so positively charged
b) Give the products and detailed mechanism for the following transformations. Be precise about arrows
and charges.
EtO2C
+
H
Ph N N N
EtO2C
H
Ph N N N
EtO2C
H
PhN3
two products, 50:50 ratio
Ph N N N
H
CO2Et
Ph N N N
H
CO2Et
3
4. Give a detailed mechanism for the following transformation, and explain why the reaction is faster in
the presence of DMAP.
MeO
Ac2O (1 eq.), Et3N (1 eq.), DMAP (cat.)
O
MeO
HO
+ DMAP
O
DMAP = N
O
O
O
O
N
O
B:
MeO
O
MeO
O
BH+
H O
O
O
O
N
N
O
Pyridine is a much poorer catalyst for this reaction. Why is the dimethylamino group on DMAP
important?
N
N
N
N
The resonance-donating dimethylamino group puts more electron density on the ring nitrogen, making it
a better nucleophile.
4