Advanced 1H NMR analysis

This is a video tutorial on advanced proton NMR analysis. By now, you will be familiar with simple
multiplicities such as singlets, doublets, triplets, quartets, quintets and so on. The relative intensity
of the lines in these multiplets is given by Pascal's triangle. Analysis is easy and makes use of the n
+ 1 multiplicity rule: If a proton NMR signal is split into n + 1 equally spaced lines, we can infer
that there will be n hydrogens nearby. Well, to be precise, what it actually means is that there are n
nearby hydrogens coupling to the signal with the same coupling constant.

So what does a coupling constant tell us? The size of a coupling constant just reveals the little bit of
extra information on the arrangement, the bond angle and even the distance between coupling
protons. For simple multiplets, the spacing between lines (measured in Hz) equals the coupling
constant J, whereas the chemical shift is usually at the geometric centre of the signal. You get the
coupling constant from an expansion of your 1H NMR spectrum. When using NMR software, make
certain that you switch to Hertz in the peak picking mode, then calculate the difference in Hertz
between the lines. The coupling partner will show the same coupling constant, and it is always
worth checking this. Coupling constants are also noted in research papers, dissertations and PhD
theses in a concise way. Typically, this includes chemical shifts, to 2 decimal places, the number of
Hs contributing to the signal, the multiplicity (usually abbreviated) and the coupling constant or
coupling constants in Hertz to one decimal place.

Most proton−proton coupling constants will be a few Hertz and only in exceptional cases reach
values as high as 20 Hz. Heteronuclear coupling constants can be much bigger. The ones you see
most often without giving them much attention are the small 13C satellites on either side of a strong
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H NMR signal. These are not impurities but are due to the coupling between protons bound to a
carbon-13.

Rotation around C-C single bonds in aliphatic alkyl chains averages out the coupling constant to
about 8 Hz. In a cyclic system rotation may be severely restricted or not occur at all. In such cases
the vicinal coupling constant depends on the angle between the coupling protons. This dependence
is described by the Karplus equation. At a 0° or 180° angle, the coupling constant reaches its
maximum value but, if the angle is 90°, coupling almost vanishes.

The size of the coupling constant also varies with the distance between the coupling protons or,
more precisely, the number of bonds between them. Geminal coupling is only found in methylene
groups in which, for some reason, the two protons HA and HB are not identical and have different
chemical shifts. The geminal or 2J coupling constant between two protons attached to the same
carbon is normally about 10 to 16 Hz, but, unfortunately, the value can vary a lot depending on the
CH2 bond angle, ring size and whether or not there is any pi system in the neighbourhood. In the
majority of cases the protons of a CH2 group are magnetically equivalent and we don't see any

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coupling at all. This changes when the protons of a CH2 group are in the neighbourhood of a chiral
centre. Then they become diastereotopic. Diastereotopic protons do not have the same chemical
shift, unless by coincidence, and hence they also couple with each other. Sometimes the protons of
a CH2 group are diastereotopic even though the molecule is not chiral. Two protons of a CH2 group
will be diastereotopic when replacement of either H would result in a second chiral centre and a pair
of diastereoisomers. The CH2 signal in this example is not a simple quartet than you might expect
from having a neighbouring CH3 group. The protons on the methylene group are diastereotopic and
have slightly different chemical shifts. They also couple to each other and, as a result, we get two
doublets of quartets.

Most vicinal coupling constants have an intermediate size. In aliphatic alkyl chains we normally see
only the vicinal 3J coupling constant with its typical value of about 6 or 7 Hz. In contrast, a long-
range coupling constant over 4 or 5 bonds is generally only observed if rotation is prevented, for
example in a conjugated or a ring system when it will be just 1 – 3 Hz in size. A zig-zag or W
arrangement between coupling protons is particularly good for enhancing long-range 4J couplings.

Let's consider the simple case of an alkene. The cis coupling constant is about 6 to 12 Hz, whereas
the corresponding trans coupling is noticeably larger with values between 12 and 18 Hz. The
coupling constant therefore allows you to distinguish a cis alkene from a trans alkene. Geminal
couplings, on the other hand, are surprisingly small. All three alkene protons of a terminal alkene
will couple with each other. Each signal splits into a doublet of doublets and shows distinct
coupling constants for the cis, the trans and the geminal coupling. You can easily recognise the
small geminal coupling. The difference in Hertz between alternating major lines corresponds to the
large trans coupling, or to the medium-sized cis coupling. This allows you to assign each signal to
the relevant alkene proton.

The spin systems discussed so far, no matter how complex-looking their multiplicity pattern, are all
first order, that is the difference in chemical shift, ∆ν, — expressed not in ppm but in the frequency
unit Hertz — is much larger than the coupling constant, J. Now, when ∆ν gets smaller and of the
order of the coupling constant, the spin system becomes strongly coupled. We say it is of higher
order. Once this happens, you can no longer analyse a multiplet by first-order methods, so forget
about the n + 1 multiplicity rule. The shape of a strongly coupled spin system depends on the
difference in chemical shift, the number of coupling nuclei involved and, funnily enough, also the
NMR spectrometer frequency.

We shall now take a look at a simple 2-spin system consisting of a proton A coupling to a proton X,
also called an AX spin system. The two letters are chosen far away in the alphabet to indicate that
the difference in chemical shift is large. In this case, our 2-spin system consists simply of two
doublets. As ∆ν becomes smaller the intensity of the outer lines begins to decrease in favour of the
inner lines. Initially it looks just like the typical roofing effect you often see in 1H NMR spectra.

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Sometimes an AB system can look like a "quartet". In other cases, you will have to take care that
you don't ignore the small outer lines or mistake them for an impurity. However, once the chemical
shifts get really close, we end up with an AB spin system, which can appear quite different to the
original two doublets. To analyse an AB system, first number the lines. The AB coupling constant
is the difference in Hz between the 1st and 2nd or the 3rd and 4th line. The chemical shifts are located
at the centre of gravity of the A and B part of the AB system and you will need to calculate their
precise positions.

While in an AB system the distance between lines still equals the coupling constant, this is, alas, no
longer the case in higher-order spin systems involving 3 or more protons. For example, the
straightforward proton NMR spectrum of a terminal alkene changes once two chemical shifts come
close together. The previously simple first-order case now complicates to an ABX, or worse an
ABC, spin system where an AB spin system couples with another proton nearby.

Chemical shifts do “shift” and will depend on temperature, concentration and solvent. In contrast,
coupling constants are constants. They remain the same, no matter whether the NMR spectrum is
recorded on a 60, 200, 300 or 400 MHz spectrometer. The multiplets may look squeezed at higher
frequency, but this is just a consequence of the ppm scale and hasn't affected the coupling constants.
However, higher-order multiplets will change when you record the NMR spectrum at another
spectrometer frequency. In the old days, when 60 or 90 MHz spectrometers were more common,
signal overlap often led to awkward higher-order spin systems. For example, the 1H NMR spectrum
of aspirin at 60 MHz looks really awful. It is, of course, of higher order. Fortunately, by taking the
spectrum on a modern high-field instrument signals are spread further apart and become first order
and much less of a headache to analyse. For this reason, you should always write down the
spectrometer frequency as part of your NMR analysis.

We will now take a closer look at coupling constants and multiplicity patterns in substituted
benzenes. The coupling constant depends, as usual, on distance: ortho coupling tends to be around 8
Hz, meta coupling is considerably smaller and typically about 1½ to 2 Hz, whereas para coupling is
so small that it can usually be ignored.

Coupling constants provide a good way for identifying the substitution pattern of a benzene. In this
example of a 1,2,4-trisubstituted benzene one H sees only one other proton nearby in ortho position:
it will give rise to a doublet with the typical 8 Hz ortho coupling. A doublet with a tiny coupling
tells us that there is a single proton nearby, in meta position. The third signal is a doublet of
doublets with an 8 Hz ortho coupling and a 1½ Hz meta coupling.

Don't forget the influence of substituents on the chemical shift. Electron-withdrawing substituents
such as a nitro or a carbonyl group shift an ortho signal downfield, to higher ppm values. The effect
is additive and two electron-withdrawing ortho substituents will push a signal even further

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downfield. An electron-donating substituent such as an OH or NH2 does just the opposite: the signal
of a proton ortho to an electron-donating substituent moves upfield, that is to smaller ppm values.

An ortho-disubstituted benzene is easily recognised. Lack of symmetry means that there will be
four distinct aromatic proton signals, two doublets of doublets and two triplets of doublets. The
doublet of doublets is due to coupling to one ortho proton and a single meta proton. A triplet of
doublets, which is more often than not a doublet of doublets of doublets, indicates that there are two
protons now in ortho position and a third in meta position. However, there is a twist. If both
substituents are identical, then the two ortho protons have the same chemical shift, and so do the
two meta protons. You might think that this simplifies matters, but far from it. The two A protons
are chemically equivalent; however, they are not magnetically equivalent and therefore still couple
to each other. Likewise the two B protons are also no longer magnetically equivalent because the
coupling constant between A and B is not the same as between A and B'. The result is an AA'BB'
[Pronounce: A A prime B B prime] or AA'XX' multiplicity, depending on whether the chemical
shifts are close to each other or not. Both spin systems are hopelessly higher order. You recognise
AA'BB' or AA'XX' spin systems by the fact that they always come in pairs. Like your hands, there
is symmetry and the two subsets are mirror images to each other. An AA'BB' multiplet consists of
up to 12 lines, some of which can be quite small. Beware that the difference in Hz between any two
lines does NOT equal any coupling constant. Analysing spectra of the AA'BB' type is not
straightforward, and you need a good NMR book. We normally won’t bother to analyse AA'BB'
spin systems, not because they are too difficult but because coupling constants in benzenes are well-
known and not very exciting.

The 1H NMR spectrum of a para-disubstituted benzene is deceptively "simple" and looks at a first
glance almost like two doublets. It is in fact another example of an AA'XX' spin system, with small
"extra" lines that are so characteristic of many more complex higher-order spectra. Again, the
pattern has a tell-tale symmetry and always comes in pairs. You should train yourself to recognise
higher-order multiplets when you see them. And always remember that analysing a higher-order
multiplet, if you fancy doing so, cannot be done using first-order rules.