What is Nuclear Magnetic Resonance - NMR

 

Nuclear spin

Resonance: 

Nuclear shielding and chemical shift:

1)  Applied magnetic field

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

Chemical shift, d :

  • This molecule has 12 equivalent protons giving rise to a single peak.
  • This peak is assigned the value = 0
  • All peaks of a sample under study are related to it and reported in parts per million.

Solvents for NMR spectroscopy:

  • NMR is carried out in solution.
  • The best solvent are usually hydrocarbons which will also produce a signal.
  • Deuterated solvent are used as these have an even number of nucleons.  These do not give a signal.
  • CDCl3 is usually used.
  • This is volatile so can be recovered by evaporation.

 

Qu 1 - 2  P85

Carbon - 13 NMR spectroscopy

Typical carbon - 13 chemical shifts:

 

              

Interpreting carbon - 13 NMR spectra

    1)    The number of different carbons

    2)    The carbon environment

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

 

Propan - 1 - ol:
  • 3 equally peaks indicating 3 different carbon environments
  • A peak at ~ 64ppm:  C - O
  • A peak at ~ 27ppm:  C - C (nearest the electronegative element O)
  • A peak at ~ 10ppm:  C - C (furthest from the electronegative O)
Propan - 2 - ol:
  • 2 different sized peaks indicating 2 different carbon environments with different amounts of carbons
  • A peak at ~ 64ppm:  C - O
  • A peak at ~ 27ppm:  C - C
  • The peak at ~ 27ppm is 2x the size of the peak of the one at ~64ppm as there are 2 equivalent carbons responsible for this peak

 

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:

Typical chemical shifts:

 

           

Integration traces:

Example:  This is the proton NMR for C3H6O2

 

 
  • 2  equally sized peaks indicating 2 different proton environments
  • This means that there are 2 areas of 3 protons
  • A) peak at ~ 3.7ppm:      O - CH3 (nearest the electronegative element O)
  • B) peak at ~ 2.2ppm:      OC - CH3 (furthest from the electronegative O)
  • Must be methyl propanoate - CH3COOCH3

 

Qu 1 - 2  P91

 

Spin - spin coupling in proton NMR spectra

Spin - Spin coupling:

Theory:

Analogy:

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

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

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

    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)

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    - OD and - NH    - 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:

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