Advanced

Pharmaceutical
Analysis
Introduction to Spectroscopy,

Pavia and Kris, 2008. The 3 rd Ed.

Spectroscopic
techniques
What do we learn?
What are spectroscopic
techniques?
Ultraviolet spectroscopy:
Visible spectroscopy
Infrared spectroscopy:
1H-NMR spectroscopy :
13C-NMR spectroscopy :

Mass spectrometry
Introduction to IR Spectroscopy
The infrared radiation is divided into three
regions as bellow:

In infrared spectroscopy, wavelength is measured in

"wavenumbers", which have the units cm-1.
Wavenumber-1 =1/ wave length in cm
Instrumentation:

Screen
flagyl
Screen
paracetamol
Screen
sulfamethoxazole
Screen
Sampling methods
In
IR spectroscopy
Film technique:
flat plate of sodium chloride
Pellet technique:
Liquid sample:
 Principle of IR spectroscopy

IR light

Sample container
What is stretching vibration?
IR light

OH C-H
3300 3000 cm-1

3300 3000
In any group of three atoms, at least two of
which are identical, there are two modes
of stretching: symmetric and asymmetric.
Examples of such groupings are -CH2, -NH2
and -NO2.
H
H H H

C
Stretching
C
Contracting
Stretching Stretching
In general, asymmetric stretching
vibrations occur at higher frequencies than
symmetric stretching vibrations.
Bending:

Bending vibrations occur at lower

frequencies than stretching
vibrations.
 Hooke s
, law
Wavenumber (cm-1) =4.12 *(K/M)1/2
K bond strength
single bond =5 × 105
double bond= 10 × 105
triple bond=15 × 105
M reduced mass
M= (M1 M2) / M1+M2
where M1 and M2 are atomic weights
With the help of Hooke,s law
determine the energy that needed to
streatch the indicated bonds in the
structre of flagyl.

O, 15.999
H, 1
C, 12.011
 Factors affecting the energy of
stretching
Wavenumber (cm )
-1 =4.12 *(K/M)1/2

C≡C C=C C-C

2150 cm-1 1650 cm-1 1200 cm-1
C-H C-C C-O C-Cl C-Br C-I
3000 cm-1 1200 cm-1 1100 cm-1 750 cm-1 600 cm-1 500 cm-1
The regions of infrared spectrum

Functional group Fingerprint

region region
Absorption of infrared light by drug
molecules:
How to identify different types of bonds
and functional groups?
Absorption of infrared light
by alkyl groups:
 1375 cm-1.

1460cm-1

n-Hexane: CH3CH2CH2CH2CH2CH3

2850-2950 cm-1
Absorption of infrared light
by alkene systems:
 1370cm-1

1465cm-1
3050 cm-1
C-H 1650 cm-1
stretching C=C
stretching
900 cm-1
C-H
bending

1-Hexene: CH2=CHCH2CH2CH2CH3
2950-2850 cm-1
C-H stretching
 890cm-1
3000-3100cm-1 1640cm-1
 H2 H2
C C
H2C CH2 HC CH2

H2C CH2 HC CH2

C C
H2 H2

1645cm-1
890cm-1
1445cm-1
3055cm-1 2936-2848cm-1
Absorption of infrared light
by alkyne systems:
Sustiva is an antiviral medication
that prevents human
immunodeficiency virus (HIV)
from multiplying in your body.
Explain how IR spectroscopy could be used
to distinguish between the following alkyne
compounds.

H3C H2
C
H3C C
H2C C CH
C
CH3
Absorption of infrared light
by aromatic rings:
Mono-substituted benzene rings

1370
 695+755

1370cm1

1470cm1
 Para-disubstituted benzene rings

CH3

1370cm-1
3100-3000cm-1 800 cm-1
CH3
1620 &1515 cm-1
 Ortho-disubstituted benzene rings

CH3

CH3
1370

3100-3000cm-1
1610 &1505 cm-1 745 cm-1
The peaks
are not clear
to be seen

1490
Meta-disubstituted benzene rings

CH3

3130cm-1 H3C 1370cm-1

1630 &1512 cm-1
775 cm-1 680 cm-1
 CH3

3130cm-1 H3C 1370cm-1

1630 &1512 cm-1
775 cm-1 680 cm-1
1370
Absorption of infrared light
by nitrile groups:

2280
Anastrozole
Cimetidine
Absorption of infrared light by
hydroxyl groups:
 1375cm-1

1460cm-1
1-Hexanol:
CH3CH2CH2CH2CH2CH2OH
1050cm-1
3325cm-1
2945-2840cm-1
 1050
Is used as a local anesthetic agent.
To flavor chewing gum and
toothpaste.
 .
1185 cm-1
*
Absorption of Infrared light by amino
groups:
3100

750 and 690

1600 & 1530

 3255
.
3000-3100 1100
1495

1580
695+755
 +

Note:
1: U have a very
+ broad peak + +
2450-3500cm-1
+ 2: 3000- +
3100cm-1 + +
+
3290

1150
Absorption of Infrared light by nitro
groups:

1523 1347 728

Furazolidone

1510

1355
3200, 2850-2950, 1470, 1355, 1185

1470
1490

1360 1355
Absorption of Infrared light by
sulfonamide groups:
 U have peaks
2850-2950
3500

1350

1150
Absorption of Infrared light by thiol
groups:

2558
1055
1055
Absorption of Infrared light by keto
groups:

O
CH3CH2C CH2CH2CH2CH3

3 - h e p ta n o n e

1713
Which of the following compounds has
lower carbonyl stretching frequency?
Cortisol is a hormone produced by the adrenal
gland that increases blood pressure, blood
glucose levels, and acts as an anti-
inflammatory agent.
 Absorption of Infrared light by
aldehyde groups:

C H
 +

Note:
1: U have a very
+ broad peak + +
2450-3500cm-1
+ 2: 3000- +
3100cm-1 + +
+
Absorption of Infrared light by
carboxyl groups:
 O
1275
C O H
Heptanoic
CH3CH2CH2CH2CH2CH2COH
O

3500 2450 1710 acid

1 - He p ta n o lic Ac id

NOTE: In carboxylic acids the hydroxy band

is much broader and appears at a lower
frequency than the OH band of an alcohol.
3500
2450

1715
Absorption of Infrared light by ester
groups:
 1240
O
1050
H2
C C
H3C O CH3
1740
Octinoxate
Absorption of Infrared light by amide
groups:
 Note:
U have peaks in
the range 3000- *
3100 cm-1, and
** *
* * 2850-2950cm-1
* *
3310
* *
1665
Explain how IR spectroscopy could be
used to help distinguish between
morphine and heroin.
Explain how IR
spectroscopy
could be used
to distinguish
between these
compounds.
Which one of the following compounds is the
most reasonable structure for the IR spectrum
shown below?
Which one of the following compounds is the most
reasonable structure for the IR spectrum shown
below?
Which of the following compounds is the most reasonable
structure for the IR spectrum shown below?
Interpret the following IR spectrum by
assigning each of the major peaks. Identify
what functional groups are present.
 Interpret the following IR spectrum by
assigning each of the major peaks.
Identify what functional groups are
present.
Suggest a possible structure for a
compound with the formula C5H7NO2 that
has the following IR spectrum and explain
your reasoning.
Which of the three compounds
below matches the IR spectra?

OH
Which of these two isomers, cyclopentane
or 1-pentene, is this the IR spectra of?

1650 cm-1
In a “matching” problem, do not try to fully analyze
each spectrum. Look for differences in the possible
compounds that will show up in an infrared spectrum.
CH3

CH3

H2 H2
CH2 C C C CH2
H

H2C CH2 H2 H2
C C CH3
CH2 CH3 H3C C C
H2 H2
2
3
4
5
6
Problem 1 HINT: Can be made from propyne
when treated with aqueous H2SO4
C3H6O and HgSO4.

1421

1715 1363
Problem 2 HINT: Can be made from
ethyl iodide and a good
C3H5N nucleophile in acetone (SN2).

2248
Problem 3 HINT: Made by adding
water to propene using
C3H8O 3M H2SO4.

1162
3345 1130 970
Problem 4
HINT: The solution to this
one is in the hydrogen
C5H10O deficiency index.

1162

3345 994
Problem 5
HINT: The solution to this
one is in the hydrogen
C7H5N deficiency index.

2178
Problem 6
HINT: The solution to this
one is in the hydrogen
C8H8O deficiency index.

1686
Problem 7
HINT: This one stinks
like rancid butter.
C4H8O2

1712
Problem 8
HINT: There are two
functional groups.
C3H4O

2121
Problem 9
HINT: The two peaks at
C7H6O 2820 and 2738 are the key.

2738
2820

1703
Problem 10

C8H8O2

1112
1724 1279