DT261/3, DT299/3

Dr. Andrew Knox

Assistant Lecturer (DIT Kevin St, School of Chemical and Pharmaceutical

Sciences). – andrew.knox@dit.ie

Adjunct Assistant Professor (School of Biochemistry & Immunology, Trinity

Biomedical Sciences Institute, Trinity College Dublin). – aknox@tcd.ie

Tel: +353 (1) 254 4082

Lab: +353 (1) 896 3959
What splitting pattern would you expect for the
signal corresponding to Hb in the molecule below?
Assume that Jab ~ Jbc. Draw a splitting diagram for
this signal, and determine the relative integration
values of each subpeak.
We can think of this signal as
being a triplet of triplets, but
because the two coupling
constants are very close, what
we would actually see is a
1,2,3,2,1 pentet.
Peak integration
 Peak integration
1) Add up all of the integrals, we get 74.3
2) Dividing each integral by the smallest one (15.2) gives a ratio of 2.38/1.0/1.50
for the three signals.
3) Multiplying by two gives 4.76/2.0/3.03, which is close to the integral numbers
(5/2/3) expected for a pure compound. N.B. there is nothing in the spectrum
that rules out 10/4/6 or higher multiples.
4) If we have a molecular formula (in this case C8H10O2S), dividing by the number
of hydrogens gives 7.4 mm per H.
5) We can then determine the number of protons corresponding to each multiplet
by rounding to the nearest integer.

So --- If given the molecular formula (C8H10O2S), we know there are 10H in
molecule
Total area: 36.2 + 15.2 + 22.8 = 74.2 mm
Thus 7.4 mm per H
36.2 / 7.4 = 4.89 i.e. 5H
15.2 / 7.4 = 2.05 i.e. 2H
22.8 / 7.4 = 3.08 i.e. 3H
Problem Set No.1
An organic compound of formula C3H8O was synthesised in a laboratory by
hydration of an alkene. The 1H NMR spectral data obtained for this compound
is given below.
Deduce its structure using this information and name it using the IUPAC
system. Refer to all of the data supplied in support of your answer.

 (ppm) Multiplicity Integration

 1.2 doublet 6H
1.9 singlet (exchanges with D2O) 1H
4.0 septet (i.e. 7 peaks) 1H
Problem Set No.1
-From molecular formula;
DBE = (8 – 8) = 0 DBE
2
Electron withdrawing atom present is oxygen

From NMR spectrum; 3 signals so 3 different types of chemically equivalent protons


 1.2, doublet, 6H. Next to 1 neighbouring H (n + 1 = number of peaks in signal where n =
number of neighbouring hydrogens). Must be two chemically equivalent –CH3 groups next
to –CH-

 1.9, singlet, 1H. Exchanges with D2O so is –OH. Doesn’t show spin-spin coupling
so get a singlet.

 4.0, septet, 1 H. Next to 6 neighbouring H’s, CH with electron withdrawing group

adjacent)

Constituent parts or “bits” are;

-OH , -CH- and 2 x -CH3 = C3H8O (so all atoms in molecular
formula are accounted for)
Put these parts together and get
2-propanol

H OH H
H C C C H
H H H
Problem Set No.2

(b) (i) Predict the 1H NMR spectrum that would be observed for 4-chloro-3-fluoro-2-pentanone,
shown below.
O
CH3 C CHCHCH3
F Cl
Ensure that you discuss the number of signals expected, the approximate chemical shift
of these signals, their integration and their splitting pattern (multiplicity) in your answer.
(ii) Sketch what the resulting 1H NMR spectrum will look like.
Problem Set No.2
(b) (i)
Chemically
O
equivalent - CHF - - CHCl - -CH3
protons: H3C C
No of signals* 4
Approx. 2.1 ppm 4-4.5 ppm 3-4 ppm 0.9 ppm
chemical shift (will be slightly
higher due to
neighbouring C-
Cl)
*no. of signals = number of types of chemically equivalent protons in the compound
Integration 3H 1H 1H 3H

Spin-spin *0 neighbouring *1 neighbouring *4 neighbouring *1 neighbouring

splitting H’s so singlet (1 H so doublet (2 Hs so quintet (5 H so doublet (2
peak) peaks) peaks) peaks)
*n = number of neighbouring protons and n + 1 = number of peaks in a signal.
NMR SPECTRA OF HYDROXYL PROTONS (-OH)
Chemical shift of hydroxyl proton reflects acidity

ROH < ArOH < RCOOH

2-5 4-7 10-12 ppm

least acidic most acidic

Quite wide range of chemical shift values.

 is sensitive to hydrogen bonding (depends on solvent and

concentration)

-OH protons undergo rapid exchange with each other. This proton
exchange is catalysed by water;
NMR SPECTRA OF HYDROXYL PROTONS (-OH) cont’d
 Usually, the signal for the hydroxyl proton is not split and spin-spin
coupling doesn’t occur so a singlet is observed (because a small
amount of water will usually be present causing rapid proton
exchange).
 Splitting of the hydroxyl proton signal into multiple peaks due to
spin-spin coupling is only observed in highly purified compounds
(e.g. freshly distilled).
The D2O Shake
 Exchangeable hydroxyl protons can be identified by the
disappearance of their 1H NMR signal on adding D2O.
 The reaction that will occur when the D2O is added to ethanol is;
Deuterium doesn’t have a nuclear spin of +1/2 so the alcohol -OH
signal is no longer observed by 1H NMR spectroscopy.
Revisiting J-Values
Revisiting J-Values
Revisiting J-Values

J is characteristic of the structure of the compound being

examined and is independent of frequency of applied field.

J depends on number, type and spatial arrangement of the bonds

separating the two nuclei.

Until now, we have only considered one type of coupling (splitting

of the signal) known as vicinal coupling, but geminal and longer
range coupling is also possible (and will be observed in many of
the examples that we’ll see in the lectures and labs- both organic
labs and spectroscopy workshop).

nJ
ab: n = number of bonds between two coupled nuclei a and b
 Revisiting J-Values
In general, the effect of coupling falls off as the number of bonds between nuclei
increases. Up until now, you have not been asked to consider coupling over more than 3
bonds as often it is not observed. Similarly, germinal coupling (through two bonds) will only
occur when the protons concerned are NOT equivalent.

However, couplings over more than 3 bonds do occur (as in the ‘w’ coupling shown below)
when there is a particularly favourable through-bond pathway (e.g. in Ar systems):
• p-Conjugation
• Rigid s-bonding skeleton

Similarly, if two protons of a methylene (CH2) group are not equivalent, they will couple
geminally.
 Revisiting J-Values; coupling constants in alkenes
3J
Ha Hb ab(cis) = 6-11 Hz
3J
ac(trans) = 12-19 Hz
2J
bc(gem) = 0-3 Hz
R Hc
The protons on the general structure shown are NOT equivalent. Make sure you
can see why this is the case.

Significantly for alkenic (vinylic) protons, the trans coupling constant is greater
than the cis coupling constant and so 1H NMR can distinguish between
diastereomeric alkenes:
Determining the Geometry of the Double Bond in
Dianisalacetone

In this example, the coupling constant of the vinylic

protons can be used to confirm that the double bond in
the compound is trans (as would be expected!).
 Two overlapping
doublets (Hv2 and
protons of para
‘Doublet’ of protons of sub. ring)
para substituted
benzene ring

Hv1:

Coupling constant?

20
Hv1:

Coupling constant:
7.718 – 7.678 =
0.040 ppm

x 400 MHz = 16 Hz

Consistent with
trans geometry
21
Since the multiplicity of a signal in which there is coupling to more
than one type of proton will vary according to the size of the
coupling constants, splitting diagrams are very useful for analysis of
first-order multiplets.

N = 6, this sextet
A quartet of triplets is what you
Multiplet would expect
(not a nonet 1:5:10:10:5:1
22
1:8:28:56:70:56:28:8:1)
 When the N+1 Rule Does NOT Apply.

Protons may be coupled to more than one type of non-equivalent

proton on neighbouring carbon atoms.

In this example, Hc is coupling to Hd and Hb. According to the N+1

rule we would anticipate a triplet (since N = 2).

However, the coupling constant between Hc and Hb (3Jcb) is larger

than that between Hc and Hd (3Jcd). In this case, a doublet of
doublets is observed.
A splitting diagram can be used to explain why the N+1 rule is not
followed and why a doublet of doublet is observed in this case.

24
You should not confuse a doublet of doublets with a
quartet. The four peaks that form a quartet should
have intensity ratio of 1:3:3:1 (Pascal’s triangle). In a
doublet of doublets, the relative intensities of the
four peaks should be 1:1:1:1
 Example: Acrylonitrile

• Use of a splitting diagram to analyse a doublet

of doublets.

• Determination of vicinal (cis and trans) and

geminal coupling constants of an alkene.
 NB: The chemical shift is the centre of the multiplet
ppm to Hz: multiply by the field,
Hz to ppm: divide by the field.

3 signals, each is a
doublet of doublets Frequency / Hz Chemical Shift /
ppm
1871
1870
1854
1853
1823
1822
1811
1810
1706
1694
1689
1677

27
A B C
 HA

Use a splitting diagram to

examine each dd and
determine the coupling
constants

28
HB

29
HC

30
 31
A B C
‘w’ coupling and a doublet of doublets.
Nitration of Veratrole to give Nitroveratrole
In this example, the ‘w’ coupling is clearly apparent and the 1H
NMR spectrum can be used to determine the regiochemical
outcome of the reaction.

A splitting tree diagram can be used to analyse the doublet of

doublets observed.
You could reasonably predict the following multiplicities
/ spin-spin splitting using the N+1 rule.
However, if we include ‘w’ coupling we then have to consider coupling
to more than one type of non-equivalent proton, and the following
would also be a reasonable prediction:
Doublet of doublets

small w coupling

35
The analysis of the spectrum of the product that results from the nitration
of veratrole demonstrates that 1H NMR is very useful in distinguishing
between two regioisomeric substituted benzene derivatives.

Learning Activity (Similar to exam question)

Examine the two regioisomeric compounds shown below. Predict the splitting
patterns in their 1H NMR spectra and determine whether 1H NMR can be used
to distinguish between them.

What characteristic splitting pattern would you expect for all para-
disubstituted benzene derivatives, assuming two different
36 substitutents?
 Exchangeable Protons

In the spectra of alcohols, the weakly acidic OH protons of an alcohol or

carboxylic acid are ionising and transfer between alcohol/acid molecules and any
traces of water in the solvent.

This process is sufficiently fast that the spectrometer only ‘sees’ an average
signal for these protons.
No coupling between these protons and others in the molecule is observed and
therefore absorptions of this type are said to be ‘decoupled by fast proton
exchange’. Signals assigned to OH protons tend to be broadened as a result. If
signal is very broad- it may even seem to disappear completely.
The exchange can be slowed by removing all traces of water and acid from the
sample and solvent or by cooling. 37
Addition of a small amount of D2O (deuterium oxide) followed by shaking of the
sample prior to running the spectrum will result in exchange of all acidic 1H for 2H
(D) and therefore the signal will disappear completely. Known as a D2O shake.

NB. Other acidic protons may also exchange

NON-FIRST ORDER SPECTRA
In non-first order spectra relative intensities of the splitting patterns
does not conform to the idealised ones predicted by Pascal’s triangle.

Non-first order spectra occur:

1) When Dn / J <15.
2) When protons are chemically equivalent but magnetically non-
equivalent (NOT DISCUSSED FURTHER THIS YEAR).

This year, all you need to be able to do is appreciate point 1) and

recognise non-first order effects in real spectra.
NON-FIRST ORDER SPECTRA

Until now we have only considered what is called ‘first-order’ splitting –

simple splitting from protons with very different chemical shifts.

These idealised spectra are only observed when the difference between the
chemical shifts of nonequivalent protons is much larger than their coupling
constant: Dd >> J.

The requirement for first order splitting is that (Dn / J ≥ 15).

If this is not the case, non-first order spectra arise and it is difficult to
interpret such spectra fully.

Increasing field strength can improve appearance as resonance frequency is

proportional to the field while J is independent of strength.
NON-FIRST ORDER SPECTRA - Roofing
When spectra are non-first order, signals may seem to lean towards each
other. This is called roofing.
1) A B 2)
A B
JAB
As ΔδdAB grows smaller
AB
w.r.t. JAB, (from 1 to 2 to
3… etc) the outer part of
the doublet appears to
100 20 Hz 100 20 Hz
diminish
3) 4)
A B A B
As Δδ gets very small,
roofing becomes severe (4
and 5).
100 20 Hz 100 20 Hz

5) 6) A (protons equiv.)
A B When Δδ = 0, HA and HB
are chemically and
magnetically equivalent
100 20 Hz Hz
and show no splitting
100 20
e.g. of Non-first order spectrum
Spectrum of 1-Chloro-4-nitrobenzene For a para-disubstituted benzene
AA’XX’ spectrum
derivative such as the one shown,
you would expect to observe a pair
of symmetrical doublets in the
aromatic region of the spectrum.

In this case, two non-first order

effects are observed and make the
spectrum look ‘messier’ than you
would otherwise expect:
1) The two doublets are roofed.
2) The small peaks near the
baseline are not impurities, they
are real.

Just be aware that real spectra are

often messier than idealized
spectra
DIASTEREOTOPIC HYDROGENS ARE CHEMICALLY
NONEQUIVALENT

Diastereotopic hydrogens are hydrogen atoms which, when one is

replaced by deuterium, will lead to the formation of one of two
possible diastereomers (3rd Year, Synthesis and Reactions).

You can identify them in organic structures as a CH2 (methylene)

group (often) adjacent to a chiral carbon atom i.e. adjacent to a
stereocentre.
These hydrogens are chemically (and magnetically) different and therefore
you will observe them as separate resonances in the proton NMR.

They will couple to each other geminally (through 2 bonds).

No symmetry operation would convert Ha to Hb in the rotamers shown

below.