Transcript Part_VI_-_Interpretation_of_Mid-IR_Spectra

Vibrational Spectroscopy for
Pharmaceutical Analysis
Part VI. Interpretation of Infrared Spectra & Applications
Rodolfo J. Romañach, Ph.D.
ENGINEERING RESEARCH CENTER FOR
STRUCTURED ORGANIC PARTICULATE SYSTEMS
RUTGERS UNIVERSITY
PURDUE UNIVERSITY
NEW JERSEY INSTITUTE OF TECHNOLOGY
UNIVERSITY OF PUERTO RICO AT MAYAGÜEZ
10/11/2005
1
Interpretation of Mid-IR Spectra
• Mid-IR spectroscopy is a powerful tool for
chemists that want to determine the structure of
a process impurity or degradation product.
2
Dividing Line
 1500 cm-1 dividing line: above 1500 cm-1 if a band has a
reasonable intensity, it is a group frequency.
 Below 1500 cm-1 the band may be either a group or
fingerprint frequency.
 Below 1500 cm-1 called the fingerprint region.
3
Group Frequencies
 Characteristic of functional groups such as -O-H,
-CH3, -COCH3, and COOH.
 Determined empirically by studying the spectra of
many related molecules.
 Always found in the spectrum of a molecule
containing that group, and always occurs in the
same narrow frequency range.
 The form of the bands is nearly always the same
in every molecule containing that group.
4
Fingerprint Frequencies
 Highly Characteristic of the Specific Molecule.
 Due to Vibrations of the Molecule as a whole.
 The numerical values cannot be predicted in most
cases.
 Valuable in characterizing a molecule.
 Fingerprint region is useful for discriminating
between molecules that resemble each other.
5
Group Frequencies
 O-H Stretch – Position is Highly Dependent on
Hydrogen Bonding.
 Intense – Easy to Identify.
 Carboxylic Acids – Very broad and strong, form
dimers.
 This band will grow in intensity if you have a
hygroscopic material.
6
Benzoic Acid Spectrum
7
Propylene Glycol – Ref. Std.
8
C-O Single Bonds
 This stretching will be observed for ethers, alcohols, esters,
anhydrides, and carboxylic acids.
 Present in carbohydrates (lactose, microcrystalline cellulose,
mannitol are commonly used in pharmaceutical processing.
 Very intense bands in 1000 – 1250 cm-1 region which are
subject to erratic shifts from small structural changes.
9
Carbohydrate Spectrum.
10
Cellulose Acetate
11
C=O Stretch
 Provides a very strong signal and is found in many
organic molecules.
 It occurs in a region of the spectrum where few other
functional groups are observed.
 Range of carbonyl frequencies is from 1750 ± 200 cm-1.
The changes in frequency have been thoroughly studied
and provide significant structural information.
12
Acetophenone
–
Notice Weak C-H stretch area in comparison with C=O
stretch
13
Corn Oil
14
KBr pellet spectrum of aromatic compound.
15
KBr pellet spectra.
16
Spectra of Two Different Crystal Habits
N.R. Sperandeo, A. Karlsson, S. Cuffini, S. Pagola, and P.W. Stephens, AAPS
PharmSciTech 2005; 6 (4) Article 82 (http://www.aapspharmscitech.org).
17
Information from PNQ Spectra
• Spectra are very similar, indicating same
compound.
• O-H and N-H were free (not involved in hydrogen
bonding) then absorbances near 3500 cm-1 would
be observed.
• The fact that N-H and O-H are near 3200 cm-1 is
indicative that they are involved in hydrogen
bonding.
• Spectra were obtained with KBr pellets
18