Nuclear Magnetic Resonance (NMR) Spectroscopy

Nuclear magnetic resonance (NMR) occurs when atomic nuclei that have spin are placed into a magnetic field; individual spins that are normally random in orientation line up parallel to the magnetic field. NMR is a property that can be used to determine the structure of molecules. Recall that the nucleus has a positive charge because it contains protons that are positively charged and neutrons that contain no charge. Just like electrons, nucleons also spin and are paired in the opposite direction. Therefore, if there is an odd number of either protons or neutrons resulting in an odd mass number, the nucleus has net spin, or nuclear spin. Nuclear spin is the magnetic moment resulting from the total angular momentum of certain nuclei, such as those with an odd number of either protons or neutrons. A nucleon is a proton or neutron in an atomic nucleus. The term is often used in nuclear chemistry when referring to the total number of protons and neutrons. Not all atoms have a nuclear spin. For example, carbon-12 contains six protons and six neutrons that have paired spins, yielding no net spin. Carbon-13, on the other hand, contains six protons and seven neutrons, yielding a net spin. Hydrogen-1 also has nuclear spin because it has one proton and no neutrons, also yielding a net spin.

As suggested by the name, nuclear magnetic resonance requires nuclear spin. Spinning atoms with charges produce a magnetic moment. A nuclear magnetic resonance spectrometer (NMR spectrometer) is an instrument that uses the magnetic moment to gain information about the structure of a compound. Individual spins that are normally random in orientation line up parallel to the applied magnetic field (with the field) or antiparallel (against the field). The energy state that is parallel to the field and requires lower energy is called the alpha state ($\alpha$-state). The energy state that is antiparallel to the field and requires higher energy is called the beta state ($\beta$-state). Protons may absorb energy to change their spin from the $\alpha$-state to the $\beta$-state. The NMR spectrometer sends pulses of radio waves through the magnetic field to provide the protons with the energy necessary to change spins. When this occurs, the proton is in resonance with the nuclear field, thus it is in nuclear magnetic resonance. Then the instrument records the energy that is released by the protons when they relax back to the $\alpha$-state from the $\beta$-state. Most NMR spectrometers range from moderately sized to large sized because they need to be large enough to create the magnetic field necessary for resonance. However, there have been advances in making the instruments smaller. Although the machine itself is quite large, it only uses 2–10 milligrams (mg) of sample in 0.6–1 milliliter (mL) of solvent. The dissolved sample is housed in a 5-millimeter (mm) NMR tube and needs to be clear in order to provide a good spectrum. A deuterated solvent is often used to dissolve the sample. A compound is deuterated when a hydrogen atom is replaced with a deuterium atom that has one proton and one neutron as compared to hydrogen that does not have any neutrons. A deuterated solvent is a liquid that is used to dissolve other substances (a solvent) that has at least one of its hydrogen atoms replaced with a deuterium atom that has one proton and one neutron as compared to hydrogen that does not have any neutrons. Deuterium (²H) is an isotope of hydrogen that contains one proton and one neutron. Using a deuterated solvent reduces the background noise of the solvent so that the peaks in the spectrum represent the protons of interest.

Third, the spectra identify the integration of each unique signal present. Integration is the intensity of the signal on a proton nuclear magnetic resonance (¹H NMR) spectrum, providing a ratio of the number of protons found in the signal. This ratio does not provide the exact number of protons but rather provides a ratio of this type of proton in this chemical environment to another type of proton in a different chemical environment.

Fourth, the spectra identify the number of neighboring protons for each signal. This information is derived from the splitting of each signal. A signal is split (or splitting) if it has multiple peaks of different areas and heights. Splitting is caused by spin-spin coupling, which is the result of the magnetic environment of one proton (or group of homotopic protons) being affected by the magnetic moment of neighboring, nonhomotopic protons.

Splitting occurs in an ${\rm {N}}+1$ pattern, where N is the number of neighboring, nonhomotopic protons found on the same or adjacent carbon atom. For example, if there is only one neighboring, nonequivalent proton (${\rm {N}}=1$), the signal is split into two equal peaks, called a doublet. Two neighboring, nonequivalent protons (${\rm {N}}=2$) produces a triplet, and three neighboring, nonequivalent protons (${\rm {N}}=3$) produces a quartet.

Multiplets may appear in NMR spectra when one nonequivalent proton is coupled to two different nonequivalent protons. This can yield very complicated NMR spectra. For example, a doublet of doublet is four lines of equal intensities that is produced by the coupling of two protons. A triplet of doublets is a pattern of doublets in which the two center peaks have twice the intensity of the other two doublets.

Consider the structure of ethyl acetate. It contains three different types of protons, which would result in three different signals. These signals will have splitting because of the nearby (neighboring) protons found in the structure.

To predict splitting, count the number of protons found on the adjacent carbon. In the case of ethyl acetate (${\rm{CH_3{-}COO{-}CH_2{-}CH_3}}$), the acetate CH₃ carbon contains three equivalent protons that are not adjacent to any protons. Splitting occurs in an ${\rm {N}}+1$ pattern, and this would result in $0+1=1$, a singlet. The carbonyl (${\rm{C{=}O}}$) carbon does not contain any protons; therefore, it would not produce a signal. The third CH₂ carbon contains two protons that are equivalent and are adjacent to three protons. This would result in $3+1=4$, a quartet. The ethyl CH₃ carbon contains three protons that are equivalent and are adjacent to two protons. Splitting occurs, and this would result in $2+1=3$, a triplet. The predicted outcome of this compound would be a singlet, a triplet, and a quartet.

The chemical shift for each of the three peaks can be predicted based on their environment. The quartet will be downfield because it is bonded to a carbon that is bonded to an oxygen atom. Oxygen atoms are electronegative, meaning that the protons on this carbon are deshielded relative to all of the other protons in the structure. The triplet will be found upfield because it is the farthest away from the electronegative atom and has a high electron density; the protons in the triplet are shielded. The singlet will fall between the triplet and the quartet because it is close to an electronegative atom but is not directly adjacent to it.

The triplet represents three protons, and so does the singlet. The total area of these two peaks should be the same to show that there are three hydrogens in each. The quartet will have an area that is two-thirds that of the other two proton groups because there is one fewer proton bonded to this carbon.

The NMR spectra of 1-bromopropane has three different types of protons, or three unique signals. The first peak at 0 ppm is the reference peak and is not a signal. One signal close to 1 ppm is a triplet, the next signal close to 2 ppm is a sextet downfield from the triplet, and the final signal at 3.4 ppm is another triplet found farther downfield. From the splitting of the signals, the triplets (${\rm {N}}+1=3;\;{\rm {N}}=2$) are both adjacent to two protons, and the sextet (${\rm {N}}+1=6;\;{\rm {N}}=5$) is adjacent to five protons.

One triplet has a chemical shift of 1 ppm, which indicates that it is part of an alkyl (alkane) group, because upfield signals between 0.8 and 2 are usually typical of alkanes. The triplet appearing at 3.4 ppm indicates it is next to a halogen or oxygen. Putting this together, the structure should be CH₃CH₂CH₂X, where X is a halogen or an oxygen. Equivalent protons in CH₃ have two neighbors and are farthest away from the halogen. Next, CH₂ has five neighbors and is nearer the halogen. Finally, CH₂X appears last, with two neighbors. The X is a halogen, specifically Br, but to know that would require more information, such as mass spec data or infrared spectroscopy (IR) data.

An NMR spectrum can differentiate between two different compounds that have the same chemical formula but different structures. For 1-bromopropane, the splitting and shift of signals in the NMR spectra can help determine to which carbon the halogen is attached. An NMR spectrum for 2-bromopropane would have two signals because there are only two types of protons because of the symmetry of the molecule. The signals are a doublet (a proton with one proton neighbor) and a septet (a proton with six proton neighbors). This makes for easy comparison between two very similar compounds, 1-bromopropane and 2-bromopropane.