Chemical Change
Chapter 2
Dr. Suzan A. Khayyat
1
types of chemical reaction
Chemical
reactions
Photochemical
Reaction
Thermal chemical
Reaction
Photooxidation Reaction
Photoaddition Reaction
Photohydrogenation
Pericyclic Reaction
Photodissociation
Dr. Suzan A. Khayyat
2
•
The Jablonski Diagram
•
The energy gained by a molecule when it absorbs a photon causes an electron to
be promoted to a higher electronic energy level. Figure 3 illustrates the principal
photophysical radiative and non-radiative processes displayed by organic
molecules in solution. The symbols So, S1, T2, etc., refer to the ground electronic
state (So), first excited singlet state (S1), second excited triplet state (T2), and so
on. The horizontal lines represent the vibrational levels of each electronic state.
Straight arrows indicate radiative transitions, and curly arrows indicate nonradiative transitions. The boxes detail the electronic spins in each orbital, with
electrons shown as up and down arrows, to distinguish their spin.
•
Note that all transitions from one electronic state to another originate from the
lowest vibrational level of the initial electronic state. For example, fluorescence
occurs only from S1, because the higher singlet states (S2, etc.) decay so rapidly by
internal conversion that fluorescence from these states cannot compete.
Dr. Suzan A. Khayyat
3
Jablonski energy diagram
Singlet State
(S 1,S2, ......)
1(n,
Triplet State
(T1, T2, ...)
Photochem.
 
A
b
s
o
r
p
t
i
o
n
F
l
u
o
r
e
s
c
e
n
c
e
ISC
Biological
Response
n 
 
photochem. &
singlet oxygen
Phosphorescence
Ground State
So
Jablonski energy diagram
Dr. Suzan A. Khayyat
4
Jablonski diagram
•
Figure 3. The basic concepts of this Jablonski diagram are presented in the Basic
Photophysics module. This version emphasizes the spins of electrons in each of
the singlet states (paired, i.e., opposite orientation, spins) compared to the
triplet states (unpaired, i.e., same orientation, spins).
Dr. Suzan A. Khayyat
5
Photochemical reactions with singlet Oxygen
1O
2
Photooxygenation Reaction
1
hv
Sens (S0)
1
Sens* (S1)
3
*
Sens (T1)
+ 3O
2
1
*
Sens (S1)
3
*
Sens (T1)
1
1
Sens (S0) + O2
Dr. Suzan A. Khayyat
9
)1O2(
1
+
g
1
g
37.5 Kcal/mol
3
g
22.4 Kcal/mol
1
Highest occupied molecular orbital of O2
Dr. Suzan A. Khayyat
10
C6H5
C6H5
H3C
N
H
N
H
H3C
N
OH
CH CH3
N
CH3
N
HOOCH2C-H2C
H
N
N
CH CH3
OH
H
N
Cl
C6H5
C6H5
Tetraphenylporphyrine (TPP)
Cl
Cl
HOOC-H2C-H2C
CH3
Hematoporphyrine( HP)
Cl
COONa
I
I
ONa
O
O
I
I
Ros Bengal(RB)
Dr. Suzan A. Khayyat
12
Criteria of an ideal sensitizer
• It must be excited by the irradiation to be
used, small singlet triplet splitting. High
ISC yield.
• It must be present in sufficient
concentration to absorb more strongly than
the other reactants under the condition.
• It must be able to transfer energy to the
desired reactant, low chemical reactivity in
Triplet state.
Types of singlet oxygen reactions
H
1
+
1)
A
O2
OOH
O
X
1
2)
+
3)
+
O2
1
O2
O
X
B
C
Dr. Suzan A. Khayyat
O
O
15
1- Ene Reaction
O*2
H
C
C
O
OH
C
C
C
C
Cis cyclic mechanism for the reaction of 1O2 with
mono-olefins.
Dr. Suzan A. Khayyat
16
Dr. Suzan A. Khayyat
17
H
OOH
C
C
C
+
1
O2
Dr. Suzan A. Khayyat
C
C
C
18
Dr. Suzan A. Khayyat
19
Dr. Suzan A. Khayyat
20
Dr. Suzan A. Khayyat
21
2-Cycloaddition Reaction (Diels Alder)
Dr. Suzan A. Khayyat
22
Direct addition reaction to produce(1,2-dioxetane)
Dr. Suzan A. Khayyat
23
Dr. Suzan A. Khayyat
24
Dr. Suzan A. Khayyat
25
Dr. Suzan A. Khayyat
26
Photosensitized oxidation
H3C
+
CH3
O
O2
hv , sens
H3C
O
O
H3C
CH3
C
H3C
C
CH3
O
H3C
+
O2
hv , sens
CH3
CH2
C
H3C
C
OOH
O
C2H5O-CH=CH-OC2H5 +
O2
hv , sens
Dr. Suzan A. Khayyat
CH3
O
C2H5O-CH-CH-OC2 H5
27
Photodissociation: processes and examples
• Hydrocarbons:
/
RCH2R +
CH2=CH2+
hv
RCR/
hv
H2 + H2C=C: (
+ H2
HC
CH)
2H + H2C=C:
H2 + HC
CH
2H + HC
CH
Dr. Suzan A. Khayyat
28
Carbonyl Compounds
1- Keetones:
• Norrish Type I:
The Norrish type I reaction is the photochemical cleavage or homolysis
of aldehydes and ketones into two free radical intermediates. The
carbonyl group accepts a photon and is excited to a photochemical
singlet state. Through intersystem crossing the triplet state can be
obtained. On cleavage of the α-carbon carbon bond from either state,
two radical fragments are obtained.
Dr. Suzan A. Khayyat
29
Norish Type I Processes of Ketones Basic
Concepts
O
O
h
C
+
R
C
O
O
O
3 X 107
2 X 106
O
O
2 X 108
1 X 108
O
2 X 107
O
1 X 107
O
O
OMe
7 X 105
not measured
>109
# Norish type I reaction is much faster for n-* compared to * excited states
# n-* reactivity is due to the weakening of the -bond by overlap of this bond with the half
vaccant n-orbital of oxygen.
# This overlap is not possible for * excited states
# Electron releasing group at para position lead to stabilization of * excited states hence decrease in reactivity
Dr. Suzan A. Khayyat
32
Dr. Suzan A. Khayyat
33
Norrish type II
• A Norrish type II reaction is the photochemical intramolecular abstraction
of a γ-hydrogen (which is a hydrogen atom three carbon positions
removed from the carbonyl group) by the excited carbonyl compound to
produce a 1,4-biradical as a primary photoproduct
Dr. Suzan A. Khayyat
34
• Norish type II photoelimination of ketones:
Cleavage of 1,4-biradicals formed by γhydrogen abstraction
O
R'
R
1 O*
h
R'
R
1 O*
R'
OH
1K
H
a
OH
R'
R'
R
R
R
n
1 O*
1K
d
O
R'
R
R'
R
1 O*
3K
d
3 O*
Kisc
R'
R
R'
R
3 O*
3K
H
O
OH
R'
OH
R'
R
R
R
n
OH
O
R
R
R'
R'
R
R'
R'
Dr. Suzan A. Khayyat
37
Dr. Suzan A. Khayyat
38
RCHO +
hv
RH +
2C2H4 +
C=O
+
CO
+
hv
CO
CO
CH2=CHCH2CH2 CHO
Dr. Suzan A. Khayyat
39
Complete the next equations
O
H2C
hv
H2C
hv
O
Dr. Suzan A. Khayyat
40
O
CH3
H3C
hv
C
H2
O
CH3
hv
H3C
CH3
CH3
Dr. Suzan A. Khayyat
41
2- Esters:
hv
RCH2CH2CH2
COOR\
RCH=CH2 +
hv
\
RCOOCH2CH2R
RCOOH
Dr. Suzan A. Khayyat
+
CH3COOR\
CH2=CHR\
42
Photocycloaddition
2+2 Intermolecular cycloaddition
O
O
R
+
hv
H3CO
H3CO
R
R\
OCH3
O
OCH3
R\
O
O
Dr. Suzan A. Khayyat
43
Dr. Suzan A. Khayyat
44
O
2
O
O
O
hv
+
O
Dr. Suzan A. Khayyat
45
2+2 Intramolecular cycloaddition
hv
Dr. Suzan A. Khayyat
46
2+4 Cycloaddition
+
Dr. Suzan A. Khayyat
47
hv
+
Dr. Suzan A. Khayyat
48
Regiochemistry of enone cycloaddition
O
CN
OEt
O
O
CN
OEt
OEt
OEt 
O
head to tail
O -
O

OEt
h

reversal of polarity
-
N
CN

O
CN
head to head
OAc
O
O
OMe
OAc
+
O
O
98%
OMe
O
O
O
OAc
O
96%
O
nBu
+
nBu
nBu
O
O
nBu OAc
only
CO2 Et
OEt
OEt
OEt
OEt
OEt
82.5
O
O
O
CO2 Et
+
EtO
81
CO2 Et
17.5
O
SiMe3
SiMe3
SiMe3
+
1
1
O
O
O
O
O
O
O
+
OAc
OAc
95
OAc
O
5
O
19
O
H
always cis
H
O
O
H
always cis
H
O
H
H
O
H
H
CuOTf, h
O
O
CuOTf, h
HO
HO
CuOTf, h
O
O
The observed selectivity is assumed to arise from
a preferential formation of the less sterically crowded
copper (I)-diene complex, leading to exo pdt.
H
H
exo pdt
O
NaIO4/RuO4
O
O
Dr. Suzan A. Khayyat
53
Photoenolization
R
R
H-Transfer
O
H
OH
O
spin-inversion
R
CO2 Me
OH
R
CH3
R
R
OH
CO2 Me
CO2 Me
CO2 Me
CO2 Me
+
CO2 Me
h
O
OH
C
Ph
Ph
.
OH
HO
Ph
Me
.
C
Me
Ph
OH
O
Ph
Ph
OH
O
OH
O
h
(-)Ephidrine
Norish II, Cleavage
Enantioselective
H-transfer
CO2 Et
O
CO2 Et
O
h
4+2
OH
O
O
O
O
O
O
O
Photoenolization
MeO
OMe
MeO
OMe
OMe
OMe
O
O
O
CO2 Et
OH
O
MeO
OMe
OMe
Podophyllotoxin derivative
Di-pi-methane rearrangement
• The di-pi-methane rearrangement is a photochemical reaction
of a molecular entity that contains two π-systems separated
by a saturated carbon atom (a 1,4-diene or an allylsubstituted aromatic ring), to form an ene- (or aryl-)
substituted cyclopropane. The rearrangement reaction
formally amounts to a 1,2 shift of one ene group (in the
diene) or the aryl group (in the allyl-aromatic analog) and
bond formation between the lateral carbons of the nonmigrating moiety.
hv
57
Oxa-Di-π-Methane rearrangement
A photochemical reaction of a β, γ-unsaturated
ketone to form a saturated α-cyclopropyl
ketone. The rearrangement formally amounts to
a 1,2-acyl shift and ‘bond formation’ between
the former α and γ carbon atoms.
hv
O
O
58
Mechanism I
Photoaddition and photocyclization
reactions
NH2
H
N
hv
H
N
+
+
+
Dr. Suzan A. Khayyat
61
Direct and photosensitized reactions
direct
trans
sensitized
cis
Dr. Suzan A. Khayyat
62
Isomerization and rearrangements
Dr. Suzan A. Khayyat
63
R
N N
R
R = Me
R=
R=
h
N N
R
R
R = CHMe
R=
R=
h
N N
N N
N
N
N
h (405nm)
h(436nm)/heat
h (313nm)
-N2
C
C
h (313nm)
-N2
N
Cis-Trans isomerization of alkenes
A
D
A
E
B
E
B
D
3S*
3
*
h
triplet
donor
h
h
sens
h
sens
h
185 nm
h
sens
h
H
H
heat
direct
Triplet
sensitized
Dr. Suzan A. Khayyat
72
hv
H
hv
H
+
+
Benzvalene
Dr. Suzan A. Khayyat
bicyclohexadiene
fulvene
73
hv
CN
C6H5
C6H5
C6H5
Dr. Suzan A. Khayyat
C6H5
CN
74
Photochemical synthesis of
oxetans
Paternò-Büchi Reaction
O
O
+
Paterno and Chieffi (1909), Buchi in 1954 mechanistic analysis
NH2
N
N
O
EtO
CO2 H
O
O N
HO
N
OH
Thromboxane A2
OEt
Oxetanocine
Insecticidal activity
HN
OAc
O
O
O
O
H2 N
Merrilactone A
O
Bradyoxetin
OH
O
O
NH2
O
OR
H
OBz OAc
Palitaxel
O
Reaction mechanism
CHO
h
ISC
[PhCHO] S1
[PhCHO] T1
(n-*)
Kisc aromatic >> Kisc aliphatic (>>1010/s)
responsible
O
O
C
C C
H
electrophile
+
O
C C
+
Biradical intermediate
nucleophile
O
O
Major
Minor
Enones and Ynones
O
O
O
+
+
42%
O
47%
O
O
Low T
+
Me
3% oxetane
+
CCl3
Me
CCl3
O
O
O
F
F
F
+
Me
+
Me
10%
O
O
O
Cl
Cl
Cl
+
Me
9 0%
+
Me
90%
10%
SiMe3
O
h
Ph
Ph
+
O
+
Ph
SiMe3
O
Ph
Ph
Ph
SiMe3
24
Ph
O
h
O
OTMS
O
+
Ph
+
Ph
1
Ph
Ph OTMS
94
O
Ph
H
Ph
+
H
SMe
OTMS
Ph
6
O
h
O
Ph
SMe
+
Ph
Ph H
100
Ph H
0
SMe
Carboxydroxylation strategy by reductive cleavage of oxetanes
R4
R4
R3
h
+
R2
R3
R CHO
R4
R2
R1
R1
Ph
OTMS
R
R
H2
O
Ph
R
OX
R3
R2
R1
CHRY
H2
O
Ph
XY
O
HO
O
O
Ph
OH
OTMS
Ph
OH
R
OH
Total synthesis of (+)-Preussin
HO
Ph
N
HO
O
O
+
Ph
H
Ph
N
Ph
PG
N
N
PG
PG
Carbohydroxylation strategy fo N-containing unsaturated heterocycles
H
PhCHO/h
R
N
CO2 Me
Ph
MeCN
H
HO
H2, Pd(OH)2/C
O
R
N
Ph
N
LAH/THF
Me
CO2 Me
endo
H2, Pd(OH)2/C
PhCHO/h
N
CO2 Me
MeCN
HO
O
LAH/THF
Ph
N
17% CO2 Me
Chem.Eur.J, 2000, 6, 3838-48
Ph
N
R
1
1
1
2
6
3
2
ortho
5
4
4
+
para
1
3
meta
Possible modes of addition in the arene-alkene photocycloaddition reactions
R
H
h
+
H
R
endo exciplex
R
Photo Fries rearrangement
Dr. Suzan A. Khayyat
84
• a Fries Rearrangement is photochemical
excitation
Dr. Suzan A. Khayyat
85
Synthetic applications of electrocyclisation reactions:
The conversion of ergosterol to vitamin D2 proceeds through a ring-opening (reverse)
electrocyclisation to give provitamin D2, which then undergoes a second rearrangement (a [1,7]sigmatropic shift). Stereochemical control in the sigmatropic shift process will be described in a
later section of this course.
H
sunlight
H
HO
ergosterol
H
photochemicallypromoted electrocyclisation
(antarafacial, conrotation)
H
provitamin D2
HO
[1,7]-sigmatropic shift.
H
HO
Dr. Suzan A. Khayyat
vitamin D2
86
DNA photochemistry
O
HN
O
NH 2
R'
260 nm (*)
N
PYRIMIDINES
270 nm (*)
N
O
R
N
R
Ura
Urd
UMP
R'=H
R'=H
R'=H
R=H
R = ribose
R = ribose phosphate
Thy
Thd
TMP
R ' = Me
R ' = Me
R ' = Me
R=H
R = deoxyribose
R = deoxyribose phosphate
Cyt
Cyd
CMP
R=H
R = ribose
R = ribose phosphate
O
NH 2
N
N
N
N
N
HN
PURINES
H 2N
N
N
R
R
Ade
Ado
AMP
R=H
R = ribose
R = ribose phosphate
Gua
Guo
GMP
R=H
R = ribose
R = ribose phosphate
O
NH 2
H
HN
N
O
NH
N
H
N
H
heat
O
N
H
N
H
O
O
O
O
O
O
O
NH
O
O
HO
O
H
O
HO
P O
O
OH
O
P O
OH
O
h
NH 2
O
O
OH
NH
N
N
h
O
HO
O
P O
O
O
OH
O
P O
O
O
N
O
O
O
HO
N
N
O
O
N
O
O
N
O
O
N
O H
N
N
N
NH 2
NH 2
O
O
OH
HO
O
P O
O
Possible photoreaction at dipyrimidine sequences (CT); cyclobutane and oxetane formation
OH
O
O
NH 2
HN
O
HN
N
N
N
N
h
N
O
HO
O
O
N
N
N
O
P O
O
O
P O
N
N
O
NH 2
N
N
O
HO
HO
OH
NH 2
O
O
O
NH 2
N
OH
O
O
N
N
O
P O
N
N
N
N
O
O
NH 2
N
O
h
N
N
O
O P O
O
NH 2
N
N
O
N
N
OH
OH
Cycloadditions involving adenine; Cyclobutane and azetidine dimer formation
Photochemistry in solution
O
H2
(CH3) C
C
H2
C
liq
(CH3)
CO +
C3H8 + H3C
CHCHO
gas
H2
(CH3)2 C
Dr. Suzan A. Khayyat
O
C
O
C
H2
C
(CH3)2
90
Photodimerization
CHO
CHO
hv
O
in open air
,CHCl3
O
OHC
1
3
\\
5
1\\
4\\
5\\
2\
OHC
2\\
6\\
O
1
O
2
4
1\
3
6\
CHO
3\
4\
5\
4
Scheme 1
Dr. Suzan A. Khayyat
91
OH
H3CO
H3CO
hv
OCH3
in open air ,CHCl3
HO
HO
2
H3CO
3\
2\
4\
HO
1\
6\
5\
OH
2
3
1
4
OCH3
5
Scheme 2
Dr. Suzan A. Khayyat
92
O
O
hv
in open air ,CHCl3
O
O
O
O
O
O
3
O
1
2
O
O 3
6
5\
O
1\
5
O
6\
4
2\
3\
4\
O
6
Scheme 3
Dr. Suzan A. Khayyat
93
Factors determining reactivity
• 1•
•
•
•
The excess energy possessed by the species (which
may help overcome activation barriers).
2- The intrinsic reactivity of the specific electronic
arrangement.
3- The relative efficiencies of the different competing
pathways for loss of the particular electronic state.
4- The type of orbital (s, p, σ, or, π, etc.) and its
symmetry.
5- Explicit in the correlation rules for orbital symmetry
and spin that are introduced first at the end of this section.
ONO
H
H
O
h
H
H
H
O
H
O
O
O
NOH
H
H
H
O
H
C
H
O
H