Conjugated Dienes and
U.V. Spectroscopy
Some Dienes
Some Conjugated Molecules
O
H
Vitamin A
O
Benzene
Cyclohex-2-enone
Prevents DNA from Unraveling
O
O
OH
OH
OH
OCH3 O
OH
O
CH3
NH2
Doxorubicin (adriamycin)
OH
Binds to DNA and inhibits the enzyme topoisomerase II
Y1 and Y2 for Ethylene
Orbital Depiction of Ethylene
Orbital Depiction
DHhydrogenation
Carbocation is Resonance
Stabilized
H
CH2=CH-CH=CH2
CH2=CH-CH-CH3
2o allylic
+

CH2
+

CH
CH CH3
Resonance Hybrid
CH2-CH=CH-CH3
1o allylic
Carbocation Stability
Conjugate Addition of HBr
CH2=CH-CH=CH2
Br
HBr
CH2=CH-CHCH3 BrCH 2-CH=CH-CH3
Br
Br
CH2=CH-CH-CH3
CH2-CH=CH-CH3
1,2- vs. 1,4-Addition
CH2=CH-CH=CH2
4
3 2 1
HBr
Br
H
H
CH2=CH-CHCH2 BrCH 2-CH=CH-CH2
2 1
4
1
kinetic
thermodynamic
forms more rapidly
is more stable
Kinetic and Thermodynamic
Products
Kinetic vs. Thermodynamic
Control
2 Different 1,4- Products Form
H-Cl 80 oC
Thermodynamic Products
Cl
CH2
H
H-Cl 80oC
H
CH2
Cl
Addition to 1,3,5-Hexatriene
Br
H
6
4
5
2
3
HBr
1,2 addition
1
Br
H
1,4-addition
not formed
H
Br
1,6-addition
At 0oC 1,2-addition is favored
At 40oC, 1,4-addition is preferred
Form more stable carbocation
Allylic Bromination With NBS
O
CH2=CHCH3 +
O
N
Br
in CCl 4, h
CH2=CHCH2Br +
O
N-Bromosuccinimide
N
O
O
O
O
Br
N H
. + Br .
N
O
Free Radical Mechanism
Mechanism involves the gradual
generation of Br2
i) CH2=CHCH3 + Br .
O
HBr +
ii)
N
.
CH2=CHCH2
O
.
.
CH2=CHCH2
+ HBr
Br 2 +
Br
.
CH2CH=CH2
CH2CH=CH2
O
N H
O
+ Br 2
CH2=CHCH2Br
.
+ Br
Resonance stabilization leads to
possibly several products
NBS, h
CCl4
4 products
.
.
.
.
Br
Br
+
+
+
Br
Br
major
Diels-Alder Reaction
a Pericyclic Reaction
CH2
H
C
C
H
C
[4+2]
cycloaddition
C
CH2
cisoid diene
H
H
EWG
H
H
dienophile
H
C
H
C
C
C
H H
EWG
C
C
H
H
adduct
H
H
EWG
Dienophiles Must be
Electron Deficient
Electron-withdrawing groups typically have
sp2 or sp atom attached to  bond
e.g.
O
C
C
C N
R
C
R = H, alkyl, OH, OR, Cl
EWG
O
CH3O
O
CH3O
heat
+
CCO2CH3
O
O
H
O
HC
H
D
O
CO2CH3
Stereochemistry
Bicyclic Adducts
endo and exo
CN
H2C=CHCN
heat
H
H
CN
H endo
exo
Endo Addition
CN
H2C=CHCN
heat
H
H
CN
H
Endo Rule
Identify the Diene and Dienophile that
gives the Adducts
O
H
CH3O
CH3O
O
H
H
H
6
O
5
H
1
2
CH3O
CH3O
O
4
3
H
H
H
retro-D.A.
O
1
CH3O
CH3O
O
dienophile
2
+
6
+
3
4
diene
diene
5
dienophile
Two Phosphatase Inhibitors
O
O
O
O
O
S
O
O
CH3
CH3
Cantharidin
H
H
LS-5
A Radiosensitizer
HOOC
O
O
OH
O
H
H
OH
O
O
OH
H
Okadaic acid
O
H
O
OH
Synthesis of LS-5
O
O
O
O
O
O
O
+
furan
O
maleic anhydride
in THF
room temp.
O
O
O
O
S
1) H2, 1%Pt/C
O
O
2) Na2S . 9H2O
O
exo adduct
Cytotoxicity
of asynchronous DU-145
prostate cancer cells
exposed to drug for
o
2-h at 37 C
Cantharidin
Cantharidic acid
LS-5
.
Survival Curves
HT-29 colon cancer cells
Irradiated after 2-h exposure
to 2 M drug
.
Control (no drug)
LS-1
LS-2
LS-5
LS-5 (1 M)
Survival Curves of
G1 phase HT-29 cells
after 2-h exposure
to LS-5
.
Control (no drug)
0.2 M
0.5 M
1.0 M
2.0 M
Radiation Inactivation
of DU-145 cells
by 4 Gy Cs-137
after treatment with
30 M drug
LS numbers
1,3-Butadiene and Ethylene
Molecular Orbitals
Proper Orbital Overlap
Overlap Must be Constructive
Unsymmetrical Diels-Alder
Reactions
OCH3
OCH3
OCH3
D
CN
or
CN
CN
OCH3
OCH3
OCH3
D
CN
or
CN
OCH3
C
N
incorrect orientation
OCH3
N
C
CN
Lewis Acid catalysis in a
Diels Alder Reaction
O
O
COCH3
COCH3
D
+
COCH3
no cat. 90%
with AlCl 3 cat. 98%
O
COCH3
10%
O
2%
AlCl3
AlCl 3
O
COCH3
Lewis acid-base complex
o
2
Intermediate is Preferred
AlCl3
O
O
COCH3
O
AlCl3
COCH3
OCH3
o
major
2
OCH3
COCH3
O
AlCl3
O
o
1
COCH3
AlCl3
minor
O
Stereochemistry in endo Addition
CH3
H
CH3
H
H
CO2CH3
H
H
endo add'n
H
H
H
H
H CO2CH3
H
H
CH3
CH3
CO2CH3
CO2CH3
Electrocyclic Reaction in
Anti-Tumor Agent
S
S
HO
S
HO
S
2
2
enzyme
O
9
7
H3COCN
O
H
O
9
7
H3COCN
OR
Calicheamycin (R = sugar)
O
H
OR
Diradical Removes H atoms from
Deoxyribose in Cancer Cell
Calicheamycin
HO
HO
S
O
S
.
O
H3COCN
O
H
.
H3COCN
OR
O
OR
H
.
o
200 C
.
[2+2] Cycloaddion is Forbidden
Photochemical [2+2] Cycloaddition
Need to Irradiate
Suprafacial – Allowed
Antarafacial - Forbidden
[4+2] is Suprafacial, hence
Allowed
Cycloaddition Reactions can be
Planned Based on the
Number of Pairs of e-’s that
Move
Formation of Cyclobutanes
h
[2+2]
H2C
CH2
A [4+6] Cycloaddition
(odd # pairs of e ’s move)
Thermally Allowed
Retro Diels-Alder, followed by
Diels-Alder
D
2
o
b.p. = 40 C
dicyclopentadiene
O
H
H
heat
O
O
O
Intramolecular photochemical
[2+2] cycloaddion
H
H
O
O
h
[2+2]
H
H
O
O
Ultraviolet Spectroscopy
The absorption of a 171-nm photon excites an electron from the p
bonding MO of ethylene to the p* antibonding MO.
Conjugated Dienes Absorb
Energy in UV Region
UV Spectrum of Isoprene
lmax = 222 nm
lmax (nm)
Conjugation lowers the energy
differences between the HOMO
and LUMO energy levels, and so
conjugated dienes absorb at longer
wavelengths than isolated dienes,
and trienes absorb at longer
wavelengths than dienes, etc.
Alkyl group substitution on
double bonds also causes
absorption to occur at longer
wavelengths.
lmax = 217nm
lmax = 232nm
217
220
223
226
227
232
240
HOMO-LUMO Gap
lessens with increased conjugation
Woodward-Fieser Rules
for Predicting lmax
Base value:
transoid diene 214 nm
cisoid diene
253 nm
Double bond extending
conjugation
Exocyclic double bond
30 nm
Alkyl group
5 nm
Cl, Br
5 nm
OH, OR
6 nm
SH, SR
30 nm
NH2, NHR, NR2
60 nm
5 nm
Predict lmax in U.V. Spectrum
OCH3
Determination of lmax
Base: 214 nm
R groups : 4 x 5 = 20 nm
exocyclic db = 5 nm
predicted lmax= 239 nm
Determination of lmax
OCH3
Base: 214 nm
double bond ext. conj. = 30 nm
OR group = 6 nm
R group = 5 nm
predicted lmax = 255 nm
Determination of lmax
Base: 253 nm
db ext. conj. = 30
R groups: 3 x 5 = 15
exocyclic db = 5
predicted lmax =303 nm