Post on 27-Oct-2014
Conjugated Dienes and U.V. Spectroscopy
Some Dienes
Some Conjugated MoleculesO
H
Vitamin A
Benzene
O
Cyclohex-2-enone
Prevents DNA from Unraveling
O
O OH
OH
OCH3
OHO
OH
O
NH2OH
CH3
Doxorubicin (adriamycin)
Binds to DNA and inhibits the enzyme topoisomerase II
andfor Ethylene
Orbital Depiction of Ethylene
Orbital Depiction
Hhydrogenation
Carbocation is Resonance Stabilized
CH2=CH-CH=CH2
HCH2=CH-CH-CH3
2o allylic
CH2-CH=CH-CH3
1o allylic
CH2 CH CH CH3
+ +
Resonance Hybrid
Carbocation Stability
Conjugate Addition of HBr
CH2=CH-CH=CH 2HBr
CH2=CH-CH-CH3 CH2-CH=CH-CH3
CH2=CH-CHCH3
Br
BrCH2-CH=CH-CH3
BrBr
1,2- vs. 1,4-Addition
1234 2 1 4 1
H H
kinetic thermodynamic
CH2=CH-CH=CH2HBr
CH2=CH-CHCH2
Br
BrCH2-CH=CH-CH2
forms more rapidly is more stable
Kinetic and Thermodynamic Products
Kinetic vs. Thermodynamic Control
2 Different 1,4- Products Form
H-Cl 80oC
Thermodynamic Products
H-Cl 80oC
CH2
H
Cl
CH2
H
Cl
Addition to 1,3,5-Hexatriene
HBr
Br
H
BrH
1,2 addition
1,6-addition
Br
H
1,4-addition
1
2
3
4
5
6
not formed
At 0oC 1,2-addition is favored
At 40oC, 1,4-addition is preferred
Form more stable carbocation
Allylic Bromination With NBS
N
O
O
BrCH2=CHCH3 +in CCl4, h
CH2=CHCH2Br N
O
O
H+
N-Bromosuccinimide
N
O
O
Br N
O
O
+ Br. .
Free Radical Mechanism
Mechanism involves the gradual generation of Br2
CH2=CHCH3
CH2=CHCH2Br
.+ Br CH2=CHCH2.
CH2CH=CH2.
+ HBr
i)
HBr + N
O
O
Br Br2 + N
O
O
H
ii).CH2CH=CH2
.CH2=CHCH2 + Br2
+ Br.
Resonance stabilization leads to possibly several products
NBS, hCCl4
. .
..
Br
Br
Br
Br
+ + +
4 products
major
Diels-Alder Reactiona Pericyclic Reaction
CH2
C
CCH2
H
H
cisoid diene
CEWGH
CHH
CC
CC
C
C
EWGHH
H
HH H
H
H
H
EWGdienophile
[4+2]
adduct
cycloaddition
Dienophiles Must be Electron Deficient
Electron-withdrawing groups typically have
C
CEWG
sp2 or sp atom attached to bond
C
O
RR = H, alkyl, OH, OR, Cl
C N
e.g.
CH3O
O
O
O
heatO
CH3OO
O
H
H
HC CCO2CH3+
CO2CH3
Stereochemistry
Bicyclic Adductsendo and exo
H2C=CHCN
CNheat
CN
H
H
H endo
exo
Endo Addition
H2C=CHCN
CNheat
CN
H
H
H
Endo Rule
Identify the Diene and Dienophile that
gives the Adducts
HH
O
O H
H
CH3OCH3O
HH
O
O H
H
CH3OCH3O
CH3O
O
CH3O
O
+
dienedienophile
retro-D.A.
+
diene dienophile
12
3 4
12
34
5
5
6
6
Two Phosphatase Inhibitors
O
O
O
O
CH3
CH3
Cantharidin
O
S
O
O
HH
LS-5
A Radiosensitizer
O
OH
HOOC
OH
OH
O
OH
HO
OH
HOH
O
O
Okadaic acid
Synthesis of LS-5
O
O
O
O
O
O
O
OO OOO
exo adduct
1) H2, 1%Pt/C
2) Na2S 9H2O.
O
S
O
O
+
in THFroom temp.
furan maleic anhydride
of asynchronous DU-145 prostate cancer cells
.CantharidinCantharidic acidLS-5
Cytotoxicity
exposed to drug for2-h at 37 C
o
Survival CurvesHT-29 colon cancer cells
Irradiated after 2-h exposure
to 2 M drug. Control (no drug)
LS-1LS-2LS-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 M0.5 M1.0 M2.0 M
Radiation Inactivationof DU-145 cellsby 4 Gy Cs-137
after treatment with 30 M drug
LS numbers
1,3-Butadiene and EthyleneMolecular Orbitals
Proper Orbital Overlap
Overlap Must be Constructive
Unsymmetrical Diels-Alder Reactions
OCH3
CN
OCH3
CN
OCH3
CN
or
OCH3
CN
OCH3
CN
OCH3
CN
or
OCH3
CN
incorrect orientation
OCH3C
N
Lewis Acid catalysis in a Diels Alder Reaction
with AlCl3 cat. 98% 2%
no cat. 90% 10%
+
COCH3
O
COCH3
O
COCH3
O
AlCl3COCH3
O
COCH3
OAlCl3
Lewis acid-base complex
2o Intermediate is Preferred
COCH3
OAlCl3
OAlCl3
OCH3
1
2
COCH3
OAlCl3 O
OCH3
AlCl3
o
o
COCH3
O
COCH3
O
major
minor
Stereochemistry in endo AdditionCH3
HH
H H
H
CO2CH3
H
endo add'n
CH3H
HH
H
CO2CH3H
HCH3
CO2CH3
CH3
CO2CH3
Electrocyclic Reaction in Anti-Tumor Agent
O
OR
H3COCN
O H
HOS S
S
Calicheamycin
enzyme
(R = sugar)
O
OR
H3COCN
O H
HO
S2
79
2
79
Diradical Removes H atoms from Deoxyribose in Cancer Cell
Calicheamycin
O
OR
H3COCN
O H
HO
S
200 C
.
.
o
O
ORH3COCN
O H
HO
S
.
.
[2+2] Cycloaddion is Forbidden
Photochemical [2+2] CycloadditionNeed 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
H2C CH2
h[2+2]
A [4+6] Cycloaddition(odd # pairs of e-’s move)
Thermally Allowed
Retro Diels-Alder, followed by Diels-Alder
dicyclopentadiene
2
b.p. = 40 Co
O
O
heat HH
O
O
Intramolecular photochemical[2+2] cycloaddion
HH
O
OH
H
O
Oh
[2+2]
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 Isoprenemax = 222 nm
240
232
227
226
223
220
217
max (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.
max = 217nm max = 232nm
Alkyl group substitution on double bonds also causes absorption to occur at longer wavelengths.
HOMO-LUMO Gap lessens with increased conjugation
Woodward-Fieser Rulesfor Predicting max
Double bond extending conjugation
30 nm
Exocyclic double bond 5 nm
Alkyl group 5 nm
Cl, Br 5 nm
OH, OR 6 nm
SH, SR 30 nm
NH2, NHR, NR2 60 nm
Base value:
transoid diene 214 nm
cisoid diene 253 nm
Predict max in U.V. Spectrum
OCH3
Determination of max
Base: 214 nm
R groups: 4 x 5 = 20 nm
exocyclic db = 5 nm
= 239 nmpredicted max
Determination of max
OCH3Base: 214 nm
double bond ext. conj. = 30 nmOR group = 6 nm
R group = 5 nm
predicted max = 255 nm
Determination of max
Base: 253 nmdb ext. conj. = 30
exocyclic db = 5R groups: 3 x 5 = 15
303 nmpredicted max =