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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 1
DIPOLAR CYCLOADDITION CHEMISTRY 1. Identify the dipole
structures from the reagents given
a
_1. NaOCl2. base
NOHN
O+
b
_
Et3NNOH
ClN
O+
c
_
O
1. NH2OH NaOAc
2. NCS3. Et3N
OCH3N
OCH3O+
d
_
O
Me H
Me-NH-OH N
Me H
O Me+
e
_
O Ph-NH-OH NPh O+
f
O
H
NH
OH
NO+_
g
_N
NH
Ph Cl
PhEt3N
N NPh Ph+
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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 2
h NNH
Cl
CO2Et
Et3N
Cl
N N CO2Et+
Cl
_
i _
NH
HN
CH3
1. POCl32. Et3N
O
N NPh CH3+
j
NHH2N
OMe
Et H
O+
N
NH
Et
MeO
_heat N
N
Et
+
MeO
H
k heat
NH NHMe Me
O+Me
N
N
Me
+
Me
Me_
l
_NH2Ph
1. NaNO2, HCl
2. NaN3NPh N N
+
m
_
1. NaNO2, HCl
2. NaN3
NH2
O
O
N
O
O
N
N
+
2. Name the class of dipole in the following reactions and give
their
structure
a Ph Ph
N
N
N
Ph
Ph
Ph
NN NPh+ _
AZIDE
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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 3
b
OO OO
O
O
ONMe
Me H
HON
Me
Me
+ _
NITRONE
c Me Me
ON
Ph
Me
Me
ONPh+
_
NITRILE OXIDE
3. Identify the dipolarophile in the following reactions and
give their
structure
a NPh N N
N
N
N
Ph
Me
Ph
+ MePh
b
Me
O
ON
MeMeCNO+
Me
O
c ON
MeMeCNO
O
Me
H
+ O
Me
4. Identify the cycloadducts from the following reactants
showing the
correct stereochemistry where appropriate. a
Ph
Ph
NPh N N+
N
N
N
Ph
Ph
Ph
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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 4
b Me Me
NPh N N+
N
N
N
Me
Me
Ph
c
OO O
NPh N N+
N
N
N
Ph O
O
O
H
H
d
Ph N N Ph
CO2Et+N
N
CO2Et
Ph
Ph
e
Me
Me
EtO2C N N Ph+
NN
Me
Me
EtO2C
Ph
f CO2Et
CPh N O+
NO
CO2Et
Ph
g Me
Me
CPh N O+
NO
Me
Me
Ph
h
N
Me H
Me MeO Me+
N
O
Me
Me
Me
Me
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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 5
i
Me
OMe
85 oC
N
O+
Me
OMe
O
N
H
H
j
exo attack
N
Ph H
O Me+ NO
Me
Ph
H
H
5. Work out the dipole and dipolarophile combination that could
be used to make
the cycloadducts given below, and......Draw the precursors and
reagent(s) needed to generate the dipoles you have identified.
a N
N
O
O Ph
Ph
N
N
O
O
Ph
Ph
+
_
+ N
NH
Ph
Ph Cl
HNNH
Ph
Ph O
b NO
tBu
Ph
OH
H
NO
tBu
Ph
O+
_
+ + NH
HO tBuO
Ph H
6. Reduction and ring opening reactions of cycloadducts
a
ON
Ph
Me
Me
H2 / Pd-COHNH2
Ph Me
Me
C=N reduced by addition of H2 to the least hindered face
b
ON
Ph
Me
Me
OHO
Ph Me
Me
Ti3+ (aq)
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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 6
c
ON
Ph
Me
Me
LiAlH4OHNH2
Ph Me
Me
C=N reduced by addition to the least hindered face
d O
N
Ph
Me
Me
NaBH4O
HN
Ph
Me
Me
7. Identify the missing dipoles, dipolarophiles and cycloadducts
in the schemes
below
a
NO
Et
O
CH2Ph
N
Et H
OH
i, NaOCl
ii, Et3N
OCH2Ph
CEt N O
b NH2Ph
Ph
Ph
i, NaNO2/ HCl
ii, NaN3
NPh N N
N
N
N
Ph
Ph
Ph
c
heat
NH2
i, NaNO2/HCl
ii, NaN3
CN
N
CN
N NN
N N
d HNNH
Ph CO2Et
EtO2C
O
i, POCl3 ii, Et3N
O
O
NN
Ph
NN
Ph
O
CO2Et
CO2Et
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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 7
e
O
H3C H
NO
H3C
CH3
i, Cl2ii, Et3N
iii.
N
H3C H
OH
CH3
NH2OH
CH3
H3C
f
NO2
Ph
excess PhNCO
O OO
CPh N O
O OO
NO
Ph
HH
g
N
EtO2C H
OHi, NCS
ii, Et3N
O
O
CEtO2C N O
O
O
O
O
NO
NO
CO2Et
CO2Et
H
H
optically active dipolarophile produces two diasteroisomeric
products
h
O
Me H
tBuNHOH N
Me H
O tBuO
N tBu
H
H Me
(exo)
i
CHOPhNHOH
N
Ph
O O
N
H
H
PhH
H
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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 8
j
ON
PhCH2 OCO2Me
NH
PhCH2 OHO
NPhCH2
CO2Me
HH
(exo)MeO2C H
(exo)
(endo)
k
OMe
OMe
N
O
H
HClH
CH2
H
N
O
H
(exo)NHOH
l
Ph
NNH
Ph
H
heat
Ph
HNN
Ph
H
Ph
NN
Ph
H
H
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HETEROCYCLIC CHEMISTRY Part 3 Modules 06710-12-14
page 9
8. The energies of the frontier molecular orbitals of two
alkenes, G and H, and benzonitrile oxide are given below. Sketch a
labelled energy diagram and indicate on it the major frontier
orbital interactions between the dipole and both dipolarophiles.
Work out from your diagram which dipolarophile will react
preferentially with the dipole.
HOMO LUMO (eV) (eV) Alkene G -10.8 +2.0 Alkene H -12.6 +1.5
Benzonitrile oxide -9.4 -0.50
Answer:
Ph C N
+3
+2
+1
0
-1
-2
-3
-4
-5
-6
-7
-8
-9
-10
-11
-0.5 eV
+2.0 eV
-9.4 eV
-10.8 eV
-12.6 eV
+1.5 eV
= 11.4 eV
= 10.9 eV
= 12.1 eV
= 10.3 eV
ALKENE H
The smallest FMO energy gap, 10.3 eV, is between the LUMOdipole
and HOMOalkene G and so the reaction with G is faster than with
alkene H.
LUMO
HOMO
O ALKENE G
-12
-13
FMO energyE / eV
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