The document discusses the interpretation of proton nuclear magnetic resonance (NMR) spectroscopy. It explains how NMR works and the information that can be obtained from NMR spectra, including the number of signals indicating different types of hydrogen atoms, peak integration revealing hydrogen ratios, and chemical shifts indicating electronic environments. It also covers spin-spin splitting patterns from neighboring hydrogen atoms. The document uses examples to illustrate concepts like chemically equivalent and non-equivalent protons, diastereotopic and enantiotopic protons, and interpretation of peak area, chemical shifts, and spin-spin splitting. It concludes that NMR spectroscopy is a useful qualitative tool for structural elucidation in pharmaceutical, chemical, and fertilizer industries.
GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry
interpretation of NMR spectroscopy
1. ACHARYA NAGARJUNA UNIVERSITY COLLEGE OF
PHARMACEUTICAL SCIENCES
PRESENTED BY
O.SASIVARDHAN
Roll.No:Y15MPH326
PHARMACEUTICAL ANALYSIS
INTERPRETATION OF NMR SPECTROSCOPY
2. Contents
1. How NMR Works
2. Information Obtained From NMR
Spectrum
3. Interpretation of NMR Spectrum
4. Conclusion
5. References
6. Information Obtain From Proton NMR
Spectrum
1. # of signals indicate the no of different
types of hydrogen's (chemical equivalence)
2. Integration or peak area indicates how many
hydrogen are in each signal. It is given in
ratio
3. Chemical shifts are given in δ (delta) values,
the Chemical shifts values indicate the
electronic environment of the hydrogen's
(shielded or de-shielded
4. Splitting patterns indicate the # of
neighbouring hydrogen's. The magnitude f the
coupling constants (J values) depend upon
the spatial relationship of the two atoms.
8. Hydrogen atoms in different environments
respond differently to the field
Each different environment of protons produce
signal in a different positions
Protons can classified as
1. Equivalent Protons
2. Non-Equivalent protons
Equivalent protons will shows single signal
Non – equivalent protons will shows more than
one signal.
1.Number Of Signals In Proton NMR
11. Replacement by some arbitrary test group
generates Diastereoisomers
Diastereotropic protons can have different
chemical shifts
Diastereotropic protons
C C
Br
H3C
H
H
d 5.3 ppm
d 5.5 ppm
Chemically Non Equivalent Protons
12. Enantiotropic protons
Are in mirror-image environments
Replacement by some arbitrary test
group generates enantiomers
Enantiotropic protons have the same
chemical shift
18. 3. 1H NMR— CHEMICAL SHIFTS
The position Of the signals in the spectrum
helps to know the nature of protons viz .
aromatic, aliphatic. Acetylinic, vinylinic,
adjacent to some electron attracting or
electron releasing group.
Each of these types of protons will have
different electronic environments and thus,
they absorb at different applied field
strengths.
When a molecule is placed in a magnetic field,
its electrons are caused to circulate and
thus, they produce secondary magnetic fields
i.e. induced magnetic field.
19. Rotation of electrons (specially pie electrons)
about the nearby nuclei generates a field that
can either oppose or reinforce the applied field
at the proton.
If the induced field opposes the applied field,
then proton is said to be Shielded*.
But, if the induced fielded reinforce (added
strength) the applied, then proton feels a higher
field and thus, such a proton is said to be
Deshielded*.
Such shifts (compared with a standard
reference) in the positions of NMR absorption
which arise due to shielding or deshielding of
protons by the electrons are called Chemical
shifts*.
The degree of shielding depends on the density
of the circulating electron.
20. Primary RCH3 0.9
Secondary R2CH2 1.3
Tertiary R3CH 1.5
Vinylic C=C-H 4.6-5.9
Allylic C=C-CH3 1.7
Chemical shifts for various types of
protons with TMS as standard reference
22. Methyl Acetate
C
O
R O
H3C C O
Base Chemical Shift = 0.87 ppm
one = 2.88 ppm
TOTAL = 3.75 ppm
O
CH3
C
O
R
Base Chemical Shift = 0.87 ppm
one = 1.23 ppm
TOTAL = 2.10 ppm
24. 24
• Spin-spin splitting occurs only between nonequivalent protons
on the same carbon or adjacent carbons.
4. 1H NMR—Spin-Spin Splitting
Let us consider how the doublet due to the CH2 group on
BrCH2CHBr2 occurs:
• When placed in an applied field, (B0), the adjacent proton
(CHBr2) can be aligned with () or against () B0. The likelihood
of either case is about 50% (i.e., 1,000,006 vs 1,000,000).
• Thus, the absorbing CH2 protons feel two slightly different
magnetic fields—one slightly larger than B0, and one slightly
smaller than B0.
• Since the absorbing protons feel two different magnetic fields,
they absorb at two different frequencies in the NMR spectrum,
thus splitting a single absorption into a doublet, where the two
peaks of the doublet have equal intensity.
25. Spin-Spin Splitting in 1H NMR Spectra
• Peaks are often split into multiple peaks due to magnetic
interactions between nonequivalent protons on adjacent carbons,
The process is called spin-spin splitting
• The splitting is into one more peak than the number of H’s on the
adjacent carbon(s), This is the “n+1 rule”
• The relative intensities are in proportion of a binomial distribution
given by Pascal’s Triangle
• The set of peaks is a multiplet (2 = doublet, 3 = triplet, 4 =
quartet, 5=pentet, 6=hextet, 7=heptet…..)
1
1 1
1 2 1
1 3 3 1
1 4 6 4 1
1 5 10 10 5 1
1 6 15 20 15 6 1
singlet
doublet
triplet
quartet
pentet
hextet
heptet
26.
27. Rules for Spin-Spin Splitting
• Equivalent protons do not split each other
• Protons that are forther than two carbon atoms apart do not
split each other
28. 28
Splitting is not generally observed between protons separated by
more than three bonds.
If Ha and Hb are not equivalent, splitting is observed when:
29.
30.
31.
32. CONCLUSION
NMR Spectrum is a qualitative tool widely used in
pharmaceutical ,chemical and fertilizer industry’s for
structural elucidation of drugs, chemical and etc.
33. REFERENCES
P.T.F. Williamson, M. Ernst, B.H. Meier: MAS Solid-
State NMR of Isotropically Enriched Biological Samples
in BioNMR in Drug Research, Ed. O. Zerbe, Wiley 2003.
R. Tycko, Biomolecular Solid State NMR: Advances in
Structural Methodology and Applications to Peptide
and Protein Fibrils, Annu. Rev. Phys. Chem. (2001), 52,
575-606.
D.D. Laws, H.-M. Bitter, A. Jerschow, Solid-State
Spectroscopic Methods in Chemistry, Angew. Chem.
(2002), 41, 3096-3129.
S.J. Opella, C. Ma, F.M. Marassi, Nuclear Magnetic
Resonance of MembraneAssociated Peptides and
Proteins, Meth. Enzymol. (2001), 339, 285-313.
34. • Derome, A.E. Modern NMR Techniques for
Chemistry Research, Pergamon: Oxford, 1987.
• Richards, S.A. Laboratory Guide to Proton
NMR Spectroscopy, Blackwell: Oxford, 1988.
• Keeler, J. Chem. Soc. Rev., 1990, 19, 381.
