Pharmaceutical Analysis &

Spectroscopy
PHAR2010

Nuclear Magnetic Resonance

Spectroscopy

-Lecture 4-

Dr Lim Kuan Hon

B1A03
Tel: 8208
KuanHon.Lim@nottingham.edu.my
Lecture Overview

Aromatic rings and the effects of substituents on

the chemical shifts of aromatic protons.
Effects of strongly withdrawing or donating groups in
aromatic rings:

In general, the aromatic protons of a benzenoid system have

resonance near 7.27 ppm.

However, the chemical shifts of the aromatic protons are

dependent on the type of substituents present.

The effects of these substituents follow the resonance and

inductive effects.
A) Electron withdrawing groups:

An electron withdrawing substituent such as nitro decreases

the electron density at the ortho and para positions of the
ring by resonance.

Note: Greater deshielding to the ortho and para protons

than those in the meta positions.
Generally, for electron withdrawing substituents: Base value of
benzenoid protons
Chemical shift (dH ppm) = 7.27 + dortho + dmeta + dpara

Example dortho dmeta dpara

Nitro (-NO2) 0.95 0.26 0.38

-COOH (carboxylic acid) 0.85 0.18 0.27

-C≡N (nitrile or cyano) 0.36 0.18 0.28

For electron withdrawing substituents:

Deshielding effects of ortho > para > meta
B) Electron donating groups:

An electron donating substituent such as amino (-NH2) would

be expected to show a reverse effect.

Note: Greater shielding to the ortho and para protons than

those in the meta positions.
Generally, for electron donating substituents:

Chemical shift (dH ppm) = 7.27 + dortho + dmeta + dpara

Example dortho dmeta dpara

Amine (-NH2) -0.75 -0.25 -0.65
Alcohol (-OH) -0.56 -0.12 -0.45
Alkoxy (-OCH3) -0.48 -0.09 -0.44
For electron donating substituents:
Shielding effects of ortho > para > meta
What about a di- or tri-substituted ring?

i.e., Electron donating

Electron withdrawing

Prediction:
HA – ortho to NO2 and NH2: the effects tend to cancel out
– expected chemical shift: ~ 7.3 ppm

HC – ortho to NO2 and para to NH2

– stronger effect from NO2
– shifted downfield from 7.3 ppm

HB – ortho to OH
– shifted upfield from 7.3 ppm
 Prediction of the chemical shifts of the aromatic protons can
also be done using the calculation below:

Chemical shift (dH ppm) = 7.27 + dortho + dmeta + dpara

dortho dmeta dpara
-NO2 0.95 0.26 0.38
-NH2 -0.75 -0.25 -0.65
-OH -0.56 -0.12 -0.45

e.g., NO2 NH2 OH

d (HA) = 7.27 + (0.95 – 0.75) + (–0.12) = 7.35 ppm

d (HB) = 7.27 + (–0.56) + (0.26 – 0.25) = 6.72 ppm

d (HC) = 7.27 + 0.95 + (–0.12) + (–0.65) = 7.45 ppm

Predict the appearance of the 1H NMR spectrum of
the following molecule:
Predict the appearance of the 1H NMR spectrum of
the following molecule:
Predict the appearance of the 1H NMR spectrum of
the following molecule: d (ppm) Integration Multiplicity
Hc 2.34 6 s
Ha 7.76 2 d (2 Hz)
Hb 7.63 1 t (2 Hz)