College of Pharmacy

Dep. of Pharmaceutical Chemistry

Organic Pharmaceutical Chemistry

18/03/2022 1
Topics to be covered:
1. Introduction to infra Red spectroscopy
2. Effects on IR bands (H-bonding effect).
3. Sampling techniques.
4. Interpretation of IR spectra.
5. Characteristic group frequencies of organic compounds.
6. Fingerprint regions.
7. Application of IR spectroscopy.
8. Problems and solutions.

18/03/2022 2
IR Spectroscopy

I. Introduction
A. Spectroscopy is the study of the interaction of matter with the
electromagnetic spectrum

1. Electromagnetic radiation displays the properties of both particles and

waves

2. The particle component is called a photon

3. The energy (E) component of a photon is proportional to the frequency.

Where h is constant and is the frequency in Hertz (cycles per
second)

E=h

4. The term is implied to mean a small, massless particle that

contains a small wave-packet of EM radiation/light we will use this
terminology in the course

18/03/2022 3
IR Spectroscopy

I. Introduction
5. Because the speed of light, c, is constant, the frequency, , (number
of cycles of the wave per second) can complete in the same time, must
be inversely proportional to how long the oscillation is, or wavelength:
c
___ hc
= ___
E=h =

c = 3 x 1010 cm/s

6. Amplitude, A, describes the wave height, or strength of the oscillation

7. Because the atomic particles in matter also exhibit wave and particle
properties (though opposite in how much) EM radiation can interact
with matter in two ways:
Collision particle-to-particle energy is lost as heat and
movement

Coupling the wave property of the radiation matches the wave

mechanical energy level

18/03/2022 4
IR Spectroscopy

I. Introduction
8. The entire electromagnetic spectrum:
Frequency, in Hz
~1019 ~1017 ~1015 ~1013 ~1010 ~105

Wavelength,
~.0001 nm ~0.01 nm 10 nm 1000 nm 0.01 cm 100 m

Energy (kcal/mol)
> 300 300-30 300-30 ~10-4 ~10-6

-rays X-rays UV IR Microwave Radio

nuclear core electronic molecular molecular Nuclear Magnetic
excitation electron excitation vibration rotation Resonance NMR
(PET) excitation ( to *) (MRI)
(X-ray
cryst.)

Visible
18/03/2022 5
IR Spectroscopy

The Electromagnetic Spectrum

18/03/2022 6
IR Spectroscopy

I. Introduction
C. The IR Spectroscopic Process:
1. The quantum mechanical energy levels observed in IR spectroscopy are
those of molecular vibrations.

2. We perceive this vibration as heat.

3. When we say a covalent bond between two atoms is of a certain

length, we are citing an average because the bond behaves as if it were
a vibrating spring connecting the two atoms.

4. For a simple diatomic molecule, this model is easy to visualize:

18/03/2022 7
IR Spectroscopy

I. Introduction
C. The IR Spectroscopic Process
5. There are two types of bond vibration:
Stretch Vibration or oscillation along the line of the bond
H H
C C
H H

symmetric asymmetric

Bend Vibration or oscillation not along the line of the bond

H H H H
C C C C
H H H
H
scissor rock twist wag
in plane out of plane

18/03/2022 8
IR Spectroscopy

Vibrational Modes for a CH2 Group

18/03/2022 9
IR Spectroscopy

C. The IR Spectroscopic Process

6.As a covalent bond oscillates due to the oscillation of the dipole of
the molecule a varying electromagnetic field is produced

7.The greater the dipole moment change through the vibration, the more
intense the EM field that is generated.

18/03/2022 11
IR Spectroscopy

Sample preparation techniques

Infrared spectra may be obtained for gases, liquids or solids (neat or
in solution)

The preparation of samples for infrared spectrometry is often the most

challenging task in obtaining an IR spectrum. Since almost all substances
absorb IR radiation at some wave length, and solvents must be carefully
chosen
18/03/2022 for the wavelength region and the sample of interest. 12
IR Spectroscopy

Gas samples
A gas sample cell consists of a cylinder of glass or sometimes a metal.
The cell is closed at both ends with an appropriate window materials
(NaCl/KBr) and equipped with valves or stopcocks for introduction of the
sample.
Long pathlength ( 10 cm) cells used to study dilute (few molecules)
or weakly absorbing samples.
Multipass cells more compact and efficient instead of long-pathlength
cells. Mirrors are used so that the beam makes several passes through
the sample before exiting the cell. (Effective pathlength 10 m).
To resolve the rotational structure of the sample, the cells must be
capable of being evacuated to measure the spectrum at reduced
pressure.
For quantitative determinations with light molecules, the cell is
sometimes pressurized in order to broaden the rotational structure and
all simpler measurement.
18/03/2022 13
IR Spectroscopy

Liquid samples
Pure or soluted in transparent solvent not water (attacks windows)

between two NaCl plates)

Adjustable pathlength (0.015 to 1 mm) by Teflon spacer

18/03/2022 14
IR Spectroscopy

Regions of transparency for common infrared solvents.

The horizontal lines indicate regions where solvent transmits at least 25% of
the incident radiation in a 1-mm cell.

18/03/2022 15
IR Spectroscopy

Solid samples
Spectra of solids are obtained as:
1. Alkali halide discs (KBr)
2. Mulls (e.g. Nujol, a highly refined mixture of saturated hydrocarbons).
3. Films (solvent or melt casting).

Alkali halide discs:.

1. A milligram or less of the fine ground sample mixed with about 100 mg of
dry KBr powder in a mortar or ball mill.
2. The mixture compressed in a die to form transparent disc.
Mulls
1. Grinding a few milligrams of the powdered sample with a mortar or with
pulverizing equipment. A few drops of the mineral oil added (grinding
continued to form a smooth paste).
2. The IR of the paste can be obtained as the liquid sample.

18/03/2022 16
IR Spectroscopy

D. The IR Spectrum
1. Each stretching and bending vibration occurs with a characteristic
frequency as the atoms and charges involved are different for different
bonds

The y-axis on an IR In regions where

spectrum is in units of no osc. bond is
% transmittance interacting with
IR light,
transmittance
In regions where the EM nears 100%
field of an osc. bond
interacts with IR light of
the same
transmittance is low
hence IR light is
absorbed.

18/03/2022 17
IR Spectroscopy

D. The IR Spectrum
2. The x-axis of the IR spectrum is in units of wavenumbers, , which is the
number of waves per centimeter in units of cm-1 (Remember E = h or E
= hc/ )

18/03/2022 18
IR Spectroscopy

D. The IR Spectrum
3. This unit is used rather than wavelength (microns) because
wavenumbers are directly proportional to the energy of transition
being observed.
High frequencies and high wavenumbers equate higher energy
is quicker to understand than Short wavelengths equate higher
energy.

4. This unit is used rather than frequency as the numbers are more

5. IR spectra are observed for the mid-infrared: wavelengths: 2.5 - 50

m, wavenumbers: 4000 - 200 cm-1

6. The peaks are Gaussian distributions of the average energy of a

transition

18/03/2022 19
IR Spectroscopy

D. The IR Spectrum
7. In general:
Lighter atoms will allow the oscillation to be faster higher energy
This is especially true of bonds to hydrogen C-H, N-H and O-H

Stronger bonds will have higher energy oscillations

Triple bonds > double bonds > single bonds in energy

Energy/ of oscillation

18/03/2022 20
IR Spectroscopy

E. The IR Spectrum The detection of different bonds

7. As opposed to chromatography or other spectroscopic methods, the
area of a IR band (or peak) is not directly proportional to
concentration of the functional group producing the peak

8. The intensity of an IR band is affected by two primary factors:

Whether the vibration is one of stretching or bending

Electronegativity difference of the atoms involved in the bond

For both effects, the greater the change in dipole moment in a

given vibration or bend, the larger the peak.

The greater the difference in electronegativity between the

atoms involved in bonding, the larger the dipole moment

Typically, stretching will change dipole moment more than

bending

18/03/2022 21
IR Spectroscopy

E. The IR Spectrum The detection of different bonds

9. It is important to make note of peak intensities to show the effect of
these factors:

Strong (s) peak is tall, transmittance is low (0-35 %)

Medium (m) peak is mid-height (75-35%)

Weak (w) peak is short, transmittance is high (90-75%)

* Broad (br) if the Gaussian distribution is abnormally broad

(*this is more for describing a bond that spans many energies)

Exact transmittance values are rarely recorded

18/03/2022 22
Infrared Spectroscopy

II. Infrared Group Analysis

A. General
1. The primary use of the IR is to detect functional groups.

2. Because the IR looks at the interaction of the EM spectrum

with actual bonds, it provides a unique qualitative probe into
the functionality of a molecule, as functional groups are
merely different configurations of different types of bonds.

3. Since most of bonds in covalent molecules have

roughly the same energy, i.e., C=C and C=O bonds, C-H
and N-H bonds they show up in similar regions of the IR
spectrum.

4. Remember all organic functional groups are made of

multiple bonds and therefore show up as multiple IR bands
(peaks)
Infrared Spectroscopy

II. Infrared Group Analysis

A. General
5. The four primary regions of the IR spectrum

Bonds to H Triple bonds Double bonds Single Bonds

Fingerprint
Region

O-H C=O C-C

N-H C=N C-N
C-H C=C C-O

4000 cm-1 2700 cm-1 2000 cm-1 1600 cm-1 600 cm-1
Infrared Spectroscopy
Octane
1. Alkanes combination of C-C and C-H bonds
C-C stretches and bends 1360-1470 cm-1

CH2-CH2 bond 1450-1470 cm-1

CH2-CH3 bond 1360-1390 cm-1

C-H of (CH3 ) between 2800-3000 cm-1

(w= weak, m= moderate, and s= strong peaks)

(w s) (m)
Infrared Spectroscopy
1-Octene
2. Alkenes addition of the C=C and vinyl C-H bonds
C=C stretch at 1620-1680 cm-1 weaker as
substitution increases

vinyl C-H stretch occurs at 3000-3100 cm-1

The difference between alkane, alkene or

alkyne C-H is important:
If the band is slightly above 3000 it is alkene or
alkyne C-H.
If it is below 3000 cm-1 it is alkane C-H.

(w m)
(w m)
Infrared Spectroscopy
1-Octyne
3. Alkynes addition of the C C and alkyne terminal C-H
bonds:
stretch 2100-2260 cm-1; strength depends on
asymmetry of bond, strongest for terminal alkynes,
weakest for symmetrical internal alkynes.

C-H for terminal alkynes occurs at 3200-3300cm-1

Internal alkynes ( R-C C-R ) would not have this band!

(w-m)

(m s)