Pharm.

451 – MEDICINAL CHEMISTRY II

INTRODUCTORY QUESTIONS
Suggest possible reasons for the following
observations.(assuming no incompatibilities)
1. A drug prepared in January 2002 with expiry
date Jan. 2005 was found to be only 15%
active(pharmacologically) barely after 6months
of manufacture (i.e. July 2002)
2. A mixture of 2 compartible compounds A &
B in benzene was very stable initially, but after
standing for some few weeks on the shelf
developed a white ppt.

3. Another preparation – an injectable, in

sealed ampoules became coloured (yellow)
after some time
 PHOTOCHEMISTRY
ENERGY OF LIGHT AND ITS TRANSFER
TO MOLECULES
The Energy (E) = hv = hc/λ ergs.

Where h= planks constant = 6.62 x 10-27ergs/sec

c= speed of light = 3 x 1010cm/sec
The Energy of light transferred to 1mole of a
substance is given by: Nhc/λ
Where N is the Avogadro No. = 6.023 x 1023
By substitution; E= 2.862x104 /λ (Kcalmole-1)

Where λ is in nm.

Thus, for a 200nm light, E = 143Kcal/mole

for a 800nm light, E = 36Kcal/mole

 ACTIVATION ENERGY
C―H bonds in methane ----101Kcalmole-1
C―C bonds in ethylene ---- 83Kcalmole-1

ELECTRONIC TRANSITIONS
1. π →π*

2. n→π*
 LOSS OF ABSORBED ENERGY
1. The molecules may return to the ground
state with the emission of light or
Fluorescence

2. The energy may be converted to Thermal

energy by collisions with other molecules
e.g. solvent molecules
3. The normal singlet excited state may
undergo electronic re-arrangement to form a
triplet excited state from which the molecules
may return to the ground state with the
emission of Phosphorescence.
4.The excited molecules either in a singlet or
triplet state can form photochemical products
by decomposition or re-arrangement of the
atoms and bonds within the molecules.
 LAWS OF PHOTOCHEMISTRY
1. GROTHUS – DRAPER LAW
Only light absorbed by a system can cause a
chemical change in the system.
The light may be absorbed by:
a. The substance giving the photochemical
change or
b. Another substance in the system leading to
photo-sensitisation.
2. STARK-EINSTEIN LAW OF PHOTOCHEMICAL
EQUIVALENCE
Each absorbed photon of light promotes the
decomposition of 1 molecule of substance.
This law is true only for primary reactions.

Quantum Efficiency (Ф) = No. of molecules formed or decomposed / No. of

photons absorbed
 EXAMPLES
a. Photolysis of acetone vapour at 120oC
Ф(form) of the CO =1

b. Photolysis of Iodine
Ф=0
I2 + hv → 2I
c. Photolysis of Hydrogen bromide
Ф(DECOP) = 2
2HBr + hv → H2 + Br2
Primary reaction:
HBr + hv → H· + Br· (Ф)= 1

Side reactions:
H· + HBr → H2 + Br·
Br· + Br· → Br2
d. Chain Reactions – OE very high
Cl2 + hv → 2Cl· Initiation
P ropa ga tion s ta ge s
.
Cl + CH 4 CH 3 . + HCl

CH3 . + Cl2 CH 3 Cl + Cl .

Te rm ina tion s ta ge s
2Cl . Cl2

.
2CH 3 CH 3 CH 3

CH 3 . + Cl
.
CH 3 Cl
 PHOTOCHEMICAL REACTIONS
ALKENES - C C

a. Isomerisation

b. Dimerisation
 ISOMERIZATION

R H R H
C C hv
C C
H R H
Tra ns R
Triple t Excite d S ta te
( Rota tion a round the s ingle bond pos s ible )
hv

H H H H
C C C C

R R R R
Cis
Ground S ta te Excite d S ta te
 OH OH

CH 3 CH 2 CH 3 CH 2

C C
hv
C C
CH 2 CH 3 CH 3 CH 2

HO OH
Cis
Tra ns S tilboe s trol

hv

O OH
CH 3 CH 2 CH 3 CH 2
e noliza tion

CH 3 CH 2 CH 3 CH 2
O OH
La mda ma x 418 P he na nthre ne mole cule
( ye llow)
 DIMERISATION

2 CH CHCOOH hv CH CH COOH

HOOC CH CH
Cinnamic acid

Truxillic acid
 CARBONYL COMPOUNDS
1. Cleavage of C-C bond adjacent to C=O
group (Norrish type I reaction)
2. Intramolecular re-arrangement involving
γ hydrogen abstraction (Norrish Type II
reaction)
3. Dimerisation
4. Photo-reduction
a. Cleavage of the C-C bond adjacent to C=O
group (Norrish Type I reaction)
O
hv . .
( a) CH 3 CCH 2 CH 3 CH3 CO + CH3 CH2

Me thyl e thyl ke tone

hv
( b)
COOH
O

Me nthone
b.Intramolecular re-arrangement involving γ
hydrogen abstraction (Norrish Type II
reaction)
c. Dimerisation of Carbonyl Compounds

O O O
CH3
CH3 CH3
hv CH3
2

CH3 CH3
O O O

2,5-dimethyl benzoquinone
d. Photo reduction of Carbonyl compounds

OH
O
CH
C
+

Benzophenone Benzhydrol

hv

OH

C. OH OH

2 ( C 6 H5 )2 C C ( C 6 H5 )2

Be nzpina col
 Nitrite Esters
H H .
CH 2 O NO CH 2 O
hv + .NO
CH 2 CH 2 CH 2 CH 2
CH 2 CH 2
a lipha tic nitrite e s te r
re a rra nge me nt
NO
.
OH CH 2 OH
CH 2
.NO
CH 2 CH 2 CH 2
CH 2
CH 2
CH 2

Is ome riza tion

OH
OH
N
CH 2
CH
CH 2 CH 2
Hydroxy Oxime compound
 Barton Reaction for the Synthesis of
aldosterone acetate from Corticosterone
acetate
CH2 OAc
CH2 OAc NO
H
C O
C O O CH2
HO
nitra tion
NOCl in pyridine

O O
Corticos te rone a ceta te Nitrite Es te r

hv OH
CH 2 OAc CH2 OAc
OH N
C O C O
O C HO CH

O
O
Aldos te rone a ce ta te 18-Hydroxy Oxime
 Aromatic Molecules
Photo oxidation
Alkenes possessing an allylic hydrogen atom
e.g. HO

O
hv +
O2 O
H
HO

( + ) Le mone ne

Re duction

H
HO

+ HO
H

Cis Tra ns

Ca rve ol
Compounds containing Cyclic hexadiene
Systems

hv o
O2 o

a lpha te rpine As ca ridole

 Catecholamines
OH
HO CH CH 2 NH CH 3

HO
Adre na line

O 2 hv

O OH

N
O
CH 3
Adre na chrom e
( Coloure d )