• All nucleons spin, and pair up just as electrons do.

• Those with an odd number of nucleons will have a nucleon that has not been able to pair up.
• A spinning nucleus such as hydrogen behaves as a spinning charge and generates a magnetic field.
• For example - ¹₁H and ¹³₆ C possess spin whereas ¹²₆C does not.
• It can be likened to a bar magnet:

• When this is placed in an external magnetic field it will align with or against the field.
• The nuclei which align parallel are at a lower energy than those aligned anti parallel:

Resonance: 

• When they are subjected to a pulse of radiofrequency radiation, some nuclei flip from parallel to anti parallel:

• This promotes the nuclei from low energy spin (parallel) to high energy spin (antiparallel) thus absorbing energy - excitation.
• The frequency required to make this happen is specific to the difference in energy between the 'parallel' and 'antiparallel'
• The excited nuclei will at some point drop back to its low energy state (parallel) emitting the same amount of energy (that is specific for those nuclei)
• As electrons surround the nuclei, the energy needed to flip the nuclei depend on the environment they find themselves.
• This pulse oscillates so the nuclei continually flip or resonate back an forth, absorbing and emitting energy.
• The resonance is recorded as a trace.
• By looking at the field strength at which the nuclei absorb energy while resonating, we can work out the structure of a molecule

Nuclear shielding and chemical shift:

• The magnetic field felt by a nucleus depends on:

1)  Applied magnetic field

2)  The weak magnetic fields generated from electrons surrounding the nuclei and nearby atoms (the environment)

• The electrons in an atom also produce tiny magnetic fields which 'shield' the nucleus from the applied magnetic field.
• This is called nuclear shielding and the extent depends upon nearby atoms or groups of atoms.
• It alters the environment of a nucleus changing the energy gap.
• Nuclei in different environments will have different chemical resonance frequencies:

Chemical shift, d :

• This is a place in the NMR spectrum where a nuclei absorbs and emits energy - resonates
• The scale is in ppm or d scale.
• The scale is measured against a reference signal, TMS = 0 chemical shift is measured from this.
• TMS is Tetramethylsilane:

Solvents for NMR spectroscopy:

Qu 1 - 2  P85

Carbon - 13 NMR spectroscopy

• 99% of any sample of carbon - ¹²C

• 1% of any sample of carbon - ¹³C

• This 1% has an uneven number of nucleons, this means it will have a magnetic spin and be detected using NMR

Typical carbon - 13 chemical shifts:

• The chemical shift indicates the environments the 'carbons' are in.

• An electronegative element causes a significant shift as carbon - 13 is sensitive to nuclear shielding.

• The scale ranges 0 - 230, this means that each carbon is likely to have its own separate signal.

• Values will vary with different solvents.

Interpreting carbon - 13 NMR spectra

• 3 things obtained from a carbon - 13 NMR is:

    1)    The number of different carbons

    2)    The carbon environment

    3)    The relative ratio of each of the types of carbons

Analysis of carbon - 13 NMR spectra

Making predictions:

Example 1:  A carbonyl compound, C₃H₆O has the following C - 13 NMR:

	3  equally sized peaks indicating 3 different carbon environments A peak at ~ 205ppm:  C = O A peak at ~ 37ppm:    C - C (nearest the electronegative element O) A peak at ~ 6ppm:      C - C (furthest from the electronegative O) Must be Propanal

Example 2:  An aromatic compound, C₈H₈O has the following C - 13 NMR:

Possible structures:
	Carbon environments	4	5	3	6
	Aromatic environments	3	4	2	4

Qu 1 - 2  P87  /  Qu 1  P89

Proton NMR spectroscopy

Proton NMR:

• Is based around the ¹H which is a single proton.

• ¹H is much more abundant than ¹³C.  99.9% ¹H to 1.1% ¹³C.

• This means less needs to be used.

• Proton NMR is done in the same way as ¹³C NMR and gives all the same information as ¹³C NMR but for protons.

• In addition - it gives you information about adjacent protons (later)

Typical chemical shifts:

• The scale is narrower which means some signals will overlap.

• Actual chemical shifts can vary depending on environments. 

• The scale should be used as a rule of thumb.

Integration traces:

• The area under the peak is proportional to the number of protons.

• On the NMR spectrum, the spectrometer measures this and is recorded as an integration trace.

• This is usually an integration line above the peak and can be measured for relative abundances.

Example:  This is the proton NMR for C₃H₆O₂

Qu 1 - 2  P91

Spin - spin coupling in proton NMR spectra

• Splitting patterns are worked out by considering the effect that adjacent, chemically different hydrogen's have on another signal in a given environment.

• The spin of the proton producing the signal is affected by each of the two forms of the adjacent hydrogen's (parallel and anti parallel).

• One orientation enhances its field and the other reduces it. 

• We can work this out by calculating the various possible combinations of alignment of adjacent protons.

Theory:

• The proton gives a signal by its magnetic field from its spin.

• Its signal is influenced by adjacent protons (on neighbouring carbons). 

• Each proton will either spin in the same direction or the opposing direction.

• This means that each adjacent proton either enhances the magnetic field or diminishes it.

• There are 2 possibilities of equal chance per adjacent proton - enhancing or diminishing the magnetic field.

• This splits the signal given by the proton

Analogy:

• Imagine you had an opinion on something.  If nobody influenced you,  your opinion would be the same.

• If another person had a view on the topic, they would either agree or disagree with you.

• Their ideas would either enhance what you thought or diminish it.

• There would be 2 possibilities of equal chance per person agreeing or disagreeing with you:

1 adjacent proton	2 adjacent proton	3 adjacent proton
The adjacent proton spins in the same or opposing direction. Agree Disagree	Each of the 2 adjacent protons spins in the same or opposing direction. Agree - Agree Agree - Disagree / Disagree - Agree Disagree - Disagree	Each of the 2 adjacent protons spins in the same or opposing direction. Agree - Agree - Agree Agree - Agree - Disagree / Disagree - Agree - Agree / Agree - Disagree - Agree Disagree - Disagree - Agree / Disagree - Agree - Disagree / Agree - Disagree - Disagree Disagree - Disagree - Disagree
2 fields of equal intensity	3 fields with an intensity of 1:2:1	4 fields with an intensity of 1:3:3:1

• There is always an extra field than the number of adjacent protons - known as the n+1 rule:

n+1 rule:

n + 1 rule:  Number of peaks = Number of different H's on adjacent atoms  +  1
1 Neighbouring H	2 Peaks	DOUBLET	1:1
2 Neighbouring H	3 Peaks	TRIPLET	1:2:1
3 Neighbouring H	4 Peaks	QUARTET	1:3:3:1
4 Neighbouring H	5 Peaks	QUINTET	1:4:6:4:1
Signals for H in an O - H bond are unaffected by hydrogen's on adjacent atoms = singlet only

NOTE:  Pascal's triangles

•  Just a note of interest.  The signal peaks show the patterns described by Pascal's triangles:

1

1     1

1     2     1

1      3     3     1

1     4     6     4     1

The proton NMR spectrum of methyl propanoate: 

• There are 3 areas of protons - this will give 3 areas of signal:

 

 

 

 

 

 

 

 

 

These protons are adjacent to = 0 protons n+1 = 1 field Singlet	These protons are adjacent to = 3 protons n+1 = 4 field Quartet	These protons are adjacent to = 2 protons n+1 = 3 field Triplet

Qu 1 - 2  P93

NMR spectra of OH and NH protons

• These are not only difficult to identify but can also confuse the rest of the spectra.

• The reason for this is:

    1)    Peaks can appear over a wide range of chemical shifts

    2)    Signals are often broad

    3)    There is no splitting pattern (due to ease of proton exchange in OH / NH - not needed)

• These signals can be removed by using heavy water, deuterium oxide, D₂O

• It is the same as water but the hydrogen's are replaced with deuterium.

• Deuterium does not give a signal in NMR

Use of D₂O

How D2O is used:   1)  An NMR is run as normal   2)  A small amount of D2O is added to the mixture, shaken and a second NMR is run The OH or NH signal disappears How it works: The Deuterium atoms in heavy water can replace the protons on OH or NH:               CH3CH2OH    +    D2O    D    CH3CH2OD    +    HOD Remember only atoms with an odd number of nucleons gives an NMR peak. This means that the - OH  à  - OD and - NH  à  - ND Deuterium has an even number of nucleons which means the - OD and - ND will no longer give a signal.

Example:  NMR spectra of ethanol, (a) CH₃CH₂OH in water and (b) in D₂O,  CH₃CH₂OD

                      THE OH SIGNAL HAS DISAPPEARED

Splitting from -OH and -NH protons:

• -OH and -NH peaks DO NOT split and DO NOT contribute to splitting

• Hydrogen bonding between water (solvent) and -OH / -NH protons broaden the peak

Qu 1-2  P95

Spin - spin coupling examples

1)  Using splitting patterns:

H - NMR of 2 isomers of C₃H₅ClO₂:  1)  CH₃CHClCOOH   and   2)  ClCH₂CH₂COOH  both run in D₂O

As it is run in D2O, we do not need to worry about the COOH signal. Quartet:  is made from proton(s) adjacent to 3H (CH-CH3) Doublet:  is made from proton(s) adjacent to 1H (CH3-CH) This leads to isomer 1)  CH3CHClCOOH     Triplet:  is made from proton(s) adjacent to 2H (CH2-CH2) As there is 2 of them, there must be 2 lots of CH2's next to each other This leads to isomer 2)  ClCH2CH2COOH

2)  Using splitting, integration and chemical shift:

H - NMR of 4 isomers of the ester, C₄H₈O₂: 

A)  CH₃CH₂COOCH₃      B)  CH₃COOCH₂CH₃        C)  HCOOCH₂CH₂CH₃      D)  HCOOCH(CH₃)₂

2 of these esters are shown below, match the ester to the spectra:

	Chemical shift:	1.1	2.1	3.6
	Integration	3	2	3
	Splitting pattern	Triplet - signal adjacent to 2H's	Quartet - signal adjacent to 3H's	Singlet - signal adjacent to 0H's
	Interpretation	3H's adjacent to 2H's	2H's adjacent to 3H's	3H's adjacent to 0H's
	Assignment	CH3CH2	O=CCH2CH3	O-CH3
	Put the assignments together:  CH3CH2COOCH3
	Chemical shift:	1.1	2.1	4.1
	Integration	3	3	2
	Splitting pattern	Triplet - signal adjacent to 2H's	Singlet - signal adjacent to 0H's	Quartet - signal adjacent to 3H's
	Interpretation	3H's adjacent to 2H's	3H's adjacent to 0H's	2H's adjacent to 3H's
	Assignment	CH3CH2	O=CCH3	O-CH2CH3
	Put the assignments together:  CH3COOCH2CH3

3)  Protons adjacent on both sides:

    The spectra below is for CH₃CHClCH₃

	Chemical shift:	1.6	3.8
	Integration	6	1
	Splitting pattern	Doublet - signal adjacent to 1H's	Heptet - signal adjacent to 6 equivalent H's
	Interpretation	6 equivalent H's adjacent to 1H's	1H's adjacent to 6 equivalent H's
	Assignment	CH3CHClCH3	CH3CHClCH3
	Put the assignments together:  CH3CHClCH3

4)  Equivalent protons not split:

    The spectra below is for ClCH₂CH₂Cl

	Chemical shift:	3.8
	Integration	4
	Splitting pattern	Singlet - signal adjacent to 2H's
	Interpretation	2H's adjacent to 6H's
	Assignment	ClCH2CH2Cl  x 2
	Put the assignments together:  ClCH2CH2Cl

Qu 1  P97

NMR in medicine

• It is used to determine the structure of synthetic drugs.
• It is used in MRI scans - Magnetic Resonance Imaging.
• The word Nuclear was dropped as it was thought people would associate it with radiation.
• The patient is the sample and although their protons are resonating, it is painless and harmless.
• Only patients with ferromagnetic metal implants (Fe, Co, Ni) should not use MRI such as pacemakers.
• MRI takes a 3D image of the water in tissue as slices which a computer then puts together. 
• Diseases affect the water in tissues and this can be identified - cancers / spinal injuries
• Used in sporting injuries to identify tendon / muscle / ligament tears as dense materials such as bones appear darker due to less protons.

Qu 1 - 4  P 99

Combined techniques:

• A single spectroscopic technique tells you 'bits' of information on the structure of a molecule or compound.
• Combining the techniques give you lots of 'bits' of information that can be used to determine the actual structure of the molecule or compound:

Mass Spectroscopy:	Chemical analysis provides the empirical formula of the compound. Mass spectroscopy gives the Mr and hence the molecular formula. Fragmentation patterns give clues about the carbon skeleton.
IR spectroscopy:	IR spectroscopy gives information about functional groups presemt in the molecule: O - H C = O C - O However many functional groups can have these bonds present
NMR spectroscopy:	Carbon - 13 NMR: Gives information about the numbers and types of carbon environments. Proton NMR: Gives information about the numbers and types of protons. It also tells you the environments the protons are in.

Worked example:

    Chemical analysis has identified the empirical formula as C₂H₄O  (Mr = 44

	IR spectra: O - H present C = O present
	Mass Spectra: Molecule has a mass, Mr = 88 Molecular formula = C4H8O2
	NMR:
	Chemical shift:	2.1	2.7	3.8	3.6
					O-H can be in any region between 1.0 - 5.5
	Integration	3	2	2	1
	Splitting pattern	Singlet - signal adjacent to 0H's	Triplet - signal adjacent to 2H's	Triplet - signal adjacent to 2H's	Singlet
	Interpretation	3H's adjacent to 0H's	2H's adjacent to 2H's	2H's adjacent to 2H's	O-H?
	Assignment	O=CCH3	O=CCH2CH2-	O-CH2CH2	-O-H
	Put the assignments together:

Qu 1-2 P103  Qu 3-8 P105  Qu 2 - 8 P108/109