Nuclear magnetic resonance spectroscopy Photographer: Dr R Campbell

NMR spectroscopy is one of the most important tools for organic chemists. It can provide information about the position of hydrogen atoms within a molecule. Nuclear magnetic resonance spectroscopy: 1 H NMR Photographer: Dr R Campbell 400 MHz NMR600 MHz NMR

Nuclear magnetic resonance spectroscopy

Many nuclei behave like a ball spinning on an axis: those of interest to organic chemists are 1 H and 13 C. Atom Nucleus (protons and neutrons): positively charged, contains most of the atom’s mass Volume around nucleus occupied by orbiting electrons e-e- e-e- e-e- e-e- e-e- NMR: the theory

Nuclei spin on their axis (like a compass needle) and therefore behave like tiny bar magnets. If an external magnetic field (B o ) (NMR spectrometer) is applied then the magnetic moments align either: with (parallel) or against (antiparallel) the applied field. BoBo Direction of rotation, or spin Direction of magnetism, or magnetic moment Totally random orientation NMR: the theory

Lower energy Higher energy The two states have slightly different energies, with the antiparallel state requiring more energy. NMR: the theory

No magnetic field Higher energy state Lower energy state EE The greater the applied magnetic field B o, the larger  E. Increasing strength of field B o ENERGY NMR: the theory

If sufficient energy is applied to the nuclei parallel to the field (low energy state) they can be flipped to the higher energy state. Energy inEnergy out detected NMR: the theory

Radio frequency generator Magnet Sample tube Radio pulse Detector Energy out detected NMR machine

 Energy required is radio frequency (60–1000 MHz).  When the nuclei are moved to a high-energy state they are said to be in resonance.  When the radio frequency stops, the nuclei that moved up fall back to their original state.  In falling back from a high-energy (resonance) state to a low- energy state, energy is given out and is detected by the NMR machine. NMR: the theory

Sample preparation The sample is dissolved in CDCl 3 or CD 3 COCD 3 (D = 3 H). The solvent should have no 1 H atoms to interfere. Absolute values are difficult to obtain, so the ppm values are obtained by reference to a standard arbitrarily assigned the δ value 0.0 ppm. The standard is tetramethylsilane (TMS).

We never deal with nuclei alone. Nuclei are always surrounded by electrons. The number and distribution of electrons is variable, depending on bonding and structure. Electrons are also charged spinning particles, therefore they have their own spin and will protect or shield the nucleus from the full effect of the magnetic field. Nucleus Spinning electron The origin of chemical shift

NMR: the theory Since different H atoms in a molecule have slightly different environments, depending on the surrounding atoms each hydrogen nucleus is shielded slightly differently. The radio frequency required to bring about resonance for each H atom will be different and the energy emitted as the nuclei relax back to the low-energy state will also be different.

Interpreting NMR spectra Every peak in an NMR spectrum represents a proton environment. The peaks in an NMR spectrum can be compared with the chemical shift in a correlation chart (data book) to identify the proton environment and the structural features of the organic compound.

As a general rule the more electron density around a hydrogen atom the closer to 0.00 ppm it will appear in the spectrum. Similarly, the less electron density the closer to ppm.

Note: If all protons absorbed and released energy in the same way only a single peak would be seen! Positions of signals: chemical shift (δ) is measured in parts per million (ppm). Interpreting NMR spectra TMS: reference material. Its H atoms are more shielded than most other organic protons. The chemical shift scale runs from right to left. The area under the peak relates to the number of protons. It is called the integral and is shown by an integration curve.

TMS (shielded) Deshielded In cyclohexane, all H are the same, therefore one peak. No strong electron-withdrawing groups, therefore near to 0.00 ppm. Integral indicates area under the peak Example 1: Cyclohexane

Example 2: Methanol There are two different environments for hydrogen: OCH 3 and ROH. 1H 3H Strong e – withdrawing group Integrals 1 to 3 ratio Deshielded Shielded

Deshielded There are three different environments for hydrogen: RCH 3, OCH 2 and ROH. Strong electronegative atom Integral 1 : 2 : 3 Example 3: Ethanol 1H 2H 3H

Example 4: Unknown sample Toluene, C 6 H 5 CH 3 There are two environments for hydrogen. The ratio of integrals is 5 to 3 Large peak ArH Small peak ArCH 3 5H 3H

Example 5: Unknown sample C 2 H 5 OBr Integral ratio 1 : 2 : 2 1H 2H

Peak 1Peak 2Peak 3 δ (ppm) Type of H–OHRCH 2 OCH 2 Hal Number of H122 Group-OH–CH 2 – –CH 2 Br Example 5: Unknown sample

Peak 1Peak 2Peak 3 δ (ppm) Type of H–OHRCH 2 OCH 2 Hal Number of H122 Group–OH–CH 2 – –CH 2 Br Example 5: Unknown sample

Example 6: N,N-diethylphenylamine C 10 H 15 N How many environments? Three hydrogen environments due to the symmetry. Sketch the spectrum. Symmetrical

Example 6: N,N-diethylphenylamine Symmetrical 5H ArH 4H NCH 2 6H RCH 3

Example 6: N,N-diethylphenylamine Peak 1Peak 2Peak 3 δ (ppm) Type of H–CH3–CH3 CH 2 –N ArH Number of H645 Group2 × –CH 3 2 × –CH 2 –N H 5 × ArH

High-resolution NMR High-resolution NMR is run using higher frequencies and more powerful magnets. The spectra produced can provide additional structural information.

High-resolution NMR Low resolution High resolution

Multiplets In high-resolution NMR it can be seen that some peaks are not single peaks but are split into more than one peak. As before the chemical shift and integral can be used to solve the structure. The splitting occurs because the protons are coupled to the neighbouring carbon’s hydrogens.

Coupling Hydrogen atoms on adjacent (neighbouring) carbon atoms can interact with each causing the peaks to split. The splitting patterns (multiplets) can provide useful evidence about which hydrogen atoms are next to each other in the molecule.

n + 1 rule The number of peaks in a multiplet is given by the n + 1 rule. n = number of protons on the neighbouring carbon atom. Next door to a CH CH 2 CH 3

High-resolution: Butanone 2H quartet 3H singlet 3H triplet CH 3 next to a carbon with no hydrogens CH 3 next to a CH 2 CH 2 next to a CH 3

Benzocaine Quartet COOCH 2 The CH 2 group must be next to a CH 3 group Triplet CH 3 The CH 3 group must be next to a CH 2 group NH2NH2 ArH Solvent/H 2 O Solvent The expanded spectrum shows the remaining peaks are multiplets

Paracetamol ArOH ArNHCO COCH 3 ArH

Magnetic Resonance Imaging Author: Jan Ainali An MRI scanner uses the principles of NMR to generate images of soft tissue.

Author: NASA Author: J Medical Case Reports 2009 Magnetic Resonance Imaging