Chemical Change

Chapter 2

Dr. Suzan A. Khayyat

types of chemical reaction

Chemical
reactions

Photochemical
Reaction

Thermal chemical
Reaction

Photooxidation Reaction

Photoaddition Reaction

Photohydrogenation

Pericyclic Reaction

Photodissociation

Dr. Suzan A. Khayyat

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

Jablonski energy diagram

Singlet State
(S1,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

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

Photochemical reactions with singlet Oxygen

1O

Photooxygenation Reaction

hv

Sens (S0)
1
Sens* (S1)
3

Sens (T1)

+ 3O

Sens (S1)
3
*
Sens (T1)
1
1
Sens (S0) + O2

Dr. Suzan A. Khayyat

)1O2(
1

+
g

g
37.5 Kcal/mol

22.4 Kcal/mol

Hi ghest occupi ed mol ecul ar orbi tal ofO2

Dr. Suzan A. Khayyat

10

C6H5

C6H5

H3C

N
H

N
H

H3C

CH3

H
N
C6H5

OH
CH CH3

HOOCH2C-H2C

N
CH CH3
OH

H
N

Cl

C6H5

Cl

Cl

Tetraphenylporphyrine (TPP)

HOOC-H2C-H2C

CH3

Hematoporphyrine( HP)

Cl

COONa
I

I
ONa

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)

O2

OOH

O
X

2)

3)

O2

O2

O
X

Dr. Suzan A. Khayyat

15

1- Ene Reaction
O*2

C
C

OH

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

O2

Dr. Suzan A. Khayyat

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

O2

hv , sens
H3C

O
O

H3C

CH3
C

H3C

CH3
O

H3C

O2

hv , sens

CH3

CH2
C

H3C

OOH

C2H5O-CH=CH-OC2H5 +

O2

hv , sens

Dr. Suzan A. Khayyat

CH3

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 -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
h

+
R

3 X 107

2 X 106

2 X 108

1 X 108

2 X 107

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 -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 hydrogen abstraction

O
R'

1 O*

R'

1 O*

R'

OH

1K
H

OH

R'

R'

R
n

1 O*

1K
d

R'

R'

R
1 O*

3K
d

3 O*

Kisc
R'

R'

3 O*

3K
H

OH

R'

OH

R'

R
n

OH
O

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\

Dr. Suzan A. Khayyat

43

Dr. Suzan A. Khayyat

44

hv
+

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

CN

OEt

CN

OEt

OEt

OEt

head to tail
O -

OEt

reversal of polarity

CN

O
CN
head to head

OAc
O

OMe

OAc

+
O

O
98%

OMe

O
OAc

96%

nBu

+
nBu

nBu
O

nBu OAc
only

CO2 Et

OEt
OEt

OEt

OEt

OEt

82.5
O

CO2 Et

+
EtO

81

CO2 Et

17.5
O

SiMe3

SiMe3

SiMe3

+
1

1
O

O
O

+
OAc

OAc

95

OAc
O
5

19

H
always cis

H
O

H
always cis

CuOTf, h
O

CuOTf, h
HO

HO

CuOTf, h

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

exo pdt

O
NaIO4/RuO4
O

Dr. Suzan A. Khayyat

53

Photoenolization
R

R
H-Transfer

O
H

OH

spin-inversion

CO2Me
OH

CH3

OH
CO2Me

CO2Me

CO2Me

CO2Me

+
CO2Me

h
O

OH

C
Ph

Ph

.
OH
HO
Ph

Me

Me

Ph
OH

O
Ph

Ph
OH

OH

(-)Ephidrine

Norish II, Cleavage

Enantioselective
H-transfer

CO 2 Et

CO 2 Et

4+2

OH

Photoenolization

MeO

OMe

MeO

OMe
OMe

OMe

O
O

CO 2 Et
OH

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 -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--Methane rearrangement
A photochemical reaction of a , -unsaturated
ketone to form a saturated -cyclopropyl
ketone. The rearrangement formally amounts to
a 1,2-acyl shift and bond formation between
the former and carbon atoms.

hv
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=

N N
R

R
R = CHMe

R=

R=

h
N N
N N

N
h (405nm)
h(436nm)/heat

h (313nm)
-N2
C

h (313nm)
-N2

Cis-Trans isomerization of alkenes

3S*

h
triplet
donor

h
sens

h
sens

h
185 nm

h
sens

heat

direct

Triplet
sensitized

Dr. Suzan A. Khayyat

72

hv

hv

Benzvalene

Dr. Suzan A. Khayyat

bicyclohexadiene

fulvene

73

hv
CN
C6H5

C6H5

C6H5

Dr. Suzan A. Khayyat

C6H5

CN

74

Photochemical synthesis of
oxetans
Patern-Bchi Reaction

O
O
+

Paterno and Chieffi (1909), Buchi in 1954 mechanistic analysis

NH2
N

O
EtO

CO 2H

O N

HO

OH
Thromboxane A2

O Et

Oxetanocine

Insecticidal activity

HN

O
O

H 2N
Merrilactone A
O

Bradyoxetin

OH

O
NH2

OAc

OR
H
OBz OAc
Palitaxel

Reaction mechanism
CHO

ISC
[PhCHO] S1

[PhCHO] T1
(n-*)

Kisc aromatic >> Kisc aliphatic (>>1010/s)

responsible

C C
H

electrophile

O
C C

Biradical intermediate

nucleophile

Major

Minor

Enones and Ynones

O

+
42%
O

47%
O

Low T

+
Me

3% oxetane

CCl3

Me

CCl3
O

+
Me

Me
10%

Cl

Cl

Cl

+
Me

9 0%

Me
90%

10%

SiMe 3

h
Ph

Ph

Ph

SiMe 3

O
Ph
Ph

Ph

SiMe 3

24

Ph

O
O TMS

Ph

Ph

Ph

Ph O TMS
94

O
Ph

H
Ph

+
H

SMe

O TMS

Ph

Ph

SMe

Ph

Ph H
100

Ph H
0

SMe

Carboxydroxylation strategy by reductive cleavage of oxetanes

R4

R4

R3

+
R2

R3

R CHO

R4

R2

R1

R1

Ph

OTMS

H2

O
Ph

OX

R3
R2
R1

CHRY

H2

O
Ph

XY

HO

Ph

OH
OTMS

Ph

OH
R

OH

Total synthesis of (+)-Preussin

HO
Ph
N
HO

+
Ph

Ph
N

Ph

PG

PG

PG

Carbohydroxylation strategy fo N-containing unsaturated heterocycles

PhCHO/h
R

CO2Me

Ph

MeCN

HO

H2, Pd(OH)2/C

O
R

Ph
N

LAH/THF

Me

CO2Me

endo

H2, Pd(OH)2/C
PhCHO/h
N
CO2Me

MeCN

HO

O
LAH/THF
Ph

N
17% CO2Me

Chem.Eur.J, 2000, 6, 3838-48

Ph

3
2
ortho

para

3
meta

Possible modes of addition in the arene-alkene photocycloaddition reactions

R
H

R
endo exciplex

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.

sunlight
H
HO
ergosterol

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

NH2

R'
260 nm (*)

PYRIMIDINES

270 nm (*)

N
O

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
NH2
N

N
N

HN
PURINES

H2N

N
R

R
Ade
Ado
AMP

R=H
R = ribose
R = ribose phosphate

Gua
Guo
GMP

R=H
R = ribose
R = ribose phosphate

NH2
H

HN

N
O

NH
N

heat

NH
N

O
O

O
HO

HO

O P O

O P O

OH

OH

h
NH2

OH
NH

O
HO

O P O
O

OH

O P O
O

O
N

O
O

HO

O
O

O
O

O H
N

NH2

NH2

O
O

OH

HO

O P O
O

Possible photoreaction at dipyrimidine sequences (CT); cyclobutane and oxetane formation

OH

NH2
HN
O

HN

N
N

HO

O P

O
O

N
N
O
O P O
O

O P O
O

NH2

O
HO

HO

OH

NH2

OH
O

NH2
N

O
O

NH2
N

O
h

N
O
O P O
O

NH2
N

N
O

OH

OH

Cycloadditions involving adenine; Cyclobutane and azetidine dimer formation

Photochemistry in solution
O
H2
(CH3) 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

OHC

\\

1\\

4\\
5\\

2\

OHC

2\\

6\\

O
1

O
2

1\

6\
CHO

3\
4\
5\

4
Scheme 1

Dr. Suzan A. Khayyat

91

OH
H3CO

H3CO
hv

OCH3

in open air ,CHCl3

HO

HO

H3CO

3\

2\

4\
HO

1\

6\
5\

OH

OCH3

5
Scheme 2

Dr. Suzan A. Khayyat

92

O
hv
in open air ,CHCl3

O 3

5\

1\
5

6\

2\
3\

4\

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, , or, , 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
NOH

H
H
O

H
O