Nuclear Magnetic Resonance (NMR)

• Nuclear Magnetic Resonance (NMR) is a spectroscopic technique used to detect energy absorbed by changes in the nuclear spin state.
• NMR gives information about the number and types of H and/or C atoms in a molecule, their connectivity, and can allow determination of the structure of a molecule.
• The NMR method was first devised by Edward Parcel and Felix Bloch, who shared the Nobel Prize in 1952 for it.

NMR Fundamentals

• Nuclei are positively charged and spin on an axis, creating a tiny magnetic field.
• Not all nuclei are suitable for NMR.
• ¹H and ¹³C are the most important NMR active nuclei in organic chemistry.
• Natural abundance of ¹H is 99.9%.
• Natural abundance of ¹³C is 1.1%.
• ¹²C is not NMR active and has a natural abundance of 98.9%.

Resonance

• Resonance involves the absorption of electromagnetic radiation by a precessing nucleus and the resulting "flip" of its nuclear spin from a lower to a higher energy state.
• Normally, nuclear magnetic fields are randomly oriented.
• When placed in an external magnetic field (B₀), the nuclear magnetic field can either align with or oppose the external magnetic field.
• The energy difference between aligned and opposed states is generally small and dependent upon B₀.
• Applied EM radiation (radio waves) causes the spin to flip, and the nuclei are said to be in resonance with B₀.
• For ¹H in an applied magnetic field of 7.05 T, the frequency of precession is approximately 300 MHz.
• For ¹³C in the same field, it is approximately 75 MHz.

Diamagnetic Current

• An applied magnetic field induces the electron density in a molecule to circulate.
• The circulation of electron density in a molecule in an applied magnetic field is called a diamagnetic current.

Shielding and Deshielding

• Shielding in NMR, also called diamagnetic shielding, refers to the reduction in magnetic field strength experienced by a nucleus underneath electron density induced to circulate when the molecule is placed in a strong magnetic field.
• Deshielding occurs when a proton is present outside the magnetic field close to an electronegative atom, requiring less applied magnetic field to cause excitation.

Shift

• Shield shift requires a higher applied field strength and shifts the absorption upfield or higher field.
• Deshield shift requires a lower applied field strength and shifts the absorption downfield or lower field.

NMR Spectrometer

• Essential elements of an NMR spectrometer include a powerful magnet, a radiofrequency generator, a radio-frequency detector, and a sample tube.
• The sample is dissolved in a solvent like carbon tetrachloride (CCl₄), deuterochloroform (CDCl₃), or deuterium oxide (D₂O). These solvents have no ¹H atoms and don't interfere in ¹H-NMR spectra.
• The sample cell is a small glass tube suspended in the magnetic field and set spinning on its long axis to ensure a homogeneous applied magnetic field.
• The absorption of electromagnetic radiation is measured as different 1H nuclei are excited from their +1/2 spin states to their -1/2 spin states.
• Frequencies at which absorption happens are in the radio frequency region of the electromagnetic spectrum.

Fourier Transform NMR (FT-NMR)

• Modern Fourier transform NMR (FT-NMR) spectrometers can significantly increase the power of the NMR technique.
• An FT-NMR spectrometer operates by holding the magnetic field constant.
• The sample is irradiated with a short pulse (approximately 10⁻⁵ s) of radio-frequency energy that flips the spins of all susceptible nuclei simultaneously.
• Each nucleus emits a sine wave at the frequency of its resonance as it returns to equilibrium.
• The intensity of the sine wave decays with time and falls to zero as nuclei return to their equilibrium state.
• A computer records this intensity-versus-time information and utilizes a mathematical algorithm called a Fourier transform (FT) to convert it to intensity-versus-frequency information.
• An FT-NMR spectrum can be recorded in less than two seconds.
• A particular advantage of FT-NMR spectroscopy is that a large number of spectra can be recorded and digitally summed to give a time-averaged spectrum.
• Instrumental electronic noise is random and partially cancels out when spectra are time-averaged, but sample signals accumulate and become stronger relative to the noise.
• Good NMR spectra can be obtained with very little sample.

Spectrum Signals

• Observed absorption frequencies are plotted as peaks relative to the TMS standard on a ppm scale.
• In a 300 MHz ¹H-NMR spectrum of methyl acetate, a small signal at d 0 is caused by the hydrogens of the TMS reference.
• The remainder of the spectrum has one signal for the three hydrogens on the methyl adjacent to oxygen, and one for the three hydrogens on the methyl adjacent to the carbonyl group.

Downfield and Upfield

• Downfield is a signal of an NMR spectrum that is shifted toward the left (larger chemical shift) on the chart paper, indicating more deshielding.
• Upfield is a signal shifted toward the right (smaller chemical shift) on the chart paper.

Equivalent Hydrogens

• "Hydrogens that have the same chemical environment."
• H atoms are equivalent if they are bonded to the same sp³ hybridized carbon atom and that carbon atom can rotate freely at room temperature.
• Identical H atoms appear on a freely rotating CH3 group or CH2 group.
• H atoms are equivalent if they are related by symmetry in a molecule.

Signal Areas/Integration

-The number of signals in a ¹H-NMR spectrum indicates the number of sets of equivalent hydrogens.

• Relative areas of these signals provide additional information.
• The intensity of the signal is proportional to the number of hydrogens in the signal.
• The vertical rise of the line of integration over each signal is proportional to the area under that signal, which shows the number of equivalent hydrogens for that signal.

¹H-NMR Integration

• The signal intensity (area under signal) is proportional to the number of protons giving rise to that signal and is shown by the integration line.
• The ratio of peak heights demonstrates the ratio of hydrogens in the signal.

Chemical Shift

• Chemical shift measures the shift in parts per million of an NMR signal relative to the signal of TMS, or it is defined as an observed frequency divided by the spectrometer’s operating frequency.
• Chemical shift is denoted by δ and has units of ppm.
• TMS (tetramethylsilane) is a universally accepted standard for ¹H-NMR and ¹³C-NMR spectroscopy assigned a chemical shift of 0.00 ppm.
• The chemical shift for a signal in a ¹H-NMR spectrum gives info on type of hydrogens giving rise to that signal.
• Hydrogens on methyl groups bonded to sp³ hybridized carbons give signals near δ 0.8 to 1.0.
• Hydrogens on methyl groups bonded to a carbonyl carbon give signals near δ 2.1 to 2.3.
• Hydrogens on a methyl group bonded to oxygen give signals near δ 3.7 to 3.9.

Factors Affecting Chemical Shift

• Electronegativity of Nearby Atoms -Electronegativity of X increases chemical shift for series CH₃-X. -The effect of an electronegative substituent falls off quickly with distance. -The effect of an electronegative substituent only 2 atoms away is only about 10% of that when it is on the adjacent atom.
• The effect of an electronegative substituent 3 atoms away is almost negligible. Electronegativity and chemical shift are related: higher electronegativity leads to reduced electron density and reduces shielding, which causes the deshielding of nuclei that makes them resonate farther downfield (i.e., with a larger chemical shift).
• Hybridization of Adjacent Atoms
• Hydrogens bonded to an sp³ hybridized carbon typically have signals at δ 0.8 to 1.7. -Vinylic hydrogens are deshielded; their signals appear at δ 4.6 to 5.7.
• Greater deshielding of vinylic hydrogens related to hybridization of carbon.
• S-bonding orbital of an sp² hybridized carbon has more s-character than s-bonding orbital of an sp³ hybridized carbon, so sp² hybridized carbon atom is more electronegative.
• Vinylic hydrogens are deshielded by electronegativity effect; nuclei appear farther downfield relative to alkyl hydrogens. Signals for acetylene and aldehyde hydrogens appear farther downfield compared with alkyl hydrogens.
• Diamagnetic Effects from Pi bonds
• Includes Alkyl, acetylenic, and vinylic
• The chemical shift of acetylenic hydrogens is 2.0 - 3.0. The chemical shift of vinylic hydrogens is 4.6 - 5.7.

Additional Factors

• Differences in chemical shifts of vinylic and acetylenic hydrogens cannot be accounted for on the basis of hybridization.
• Influence is magnetic induction from p bonds.
• An applied magnetic field causes the pi electrons of an aromatic ring to circulate, creating a ring current and an associated magnetic field.
• The magnetic field opposes the applied field in the middle of the ring but reinforces the applied field on the outside of the ring.

Signal Splitting and the (n+1) Rule

• Signal splitting is set of peak by influence of non equivalent nuclei on same or adjacent atom. -According to the (n+1) rule, if a hydrogen has n hydrogens nonequivalent to it but equivalent among themselves on the same or adjacent atom(s), its ¹H-NMR signal is split into (n + 1) peaks.
• For the spectrum of 1,1-dichloroethane, the three hydrogens of -CH3 group have 1 nonequivalent neighbor hydrogen (n = 1), making their signal a doublet. The single hydrogen of the -CHCl2 group has a set of 3 nonequivalent neighbor hydrogens (n = 3), splitting the signal into a quartet.

Kinds of Information

• Number of signals informs of the number of sets of equivalent hydrogens.
• Integration of signal areas indicates of the relative numbers of hydrogens.
• The chemical shift of each signal relates to the types of hydrogens.