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Proton nuclear magnetic resonance (proton NMR, hydrogen-1 NMR, or 1H NMR) is the application of
nuclear magnetic resonance Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with a ...
in
NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...
with respect to
hydrogen-1 Hydrogen (1H) has three naturally occurring isotopes, sometimes denoted , , and . and are stable, while has a half-life of years. Heavier isotopes also exist, all of which are synthetic and have a half-life of less than one zeptosecond (10āˆ ...
nuclei within the
molecules A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...
of a substance, in order to determine the structure of its molecules. In samples where natural
hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, an ...
(H) is used, practically all the hydrogen consists of the
isotope Isotopes are two or more types of atoms that have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), and that differ in nucleon numbers (mass numbers) ...
1H (hydrogen-1; i.e. having a
proton A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the protonā€“electron mass ...
for a nucleus). Simple NMR spectra are recorded in
solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Soluti ...
, and
solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
protons must not be allowed to interfere.
Deuterated Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific ...
(deuterium = 2H, often symbolized as D) solvents especially for use in NMR are preferred, e.g. deuterated water, D2O, deuterated
acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...
, (CD3)2CO, deuterated
methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...
, CD3OD, deuterated dimethyl sulfoxide, (CD3)2SO, and
deuterated chloroform Deuterated chloroform, also known as chloroform-''d'', is the organic compound with the formula C2HCl3 or . Deuterated chloroform is a common solvent used in NMR spectroscopy. The properties of are virtually identical. Preparation Deuterated ch ...
, CDCl3. However, a solvent without hydrogen, such as
carbon tetrachloride Carbon tetrachloride, also known by many other names (such as tetrachloromethane, also IUPAC nomenclature of inorganic chemistry, recognised by the IUPAC, carbon tet in the cleaning industry, Halon-104 in firefighting, and Refrigerant-10 in HVAC ...
, CCl4 or
carbon disulfide Carbon disulfide (also spelled as carbon disulphide) is a neurotoxic, colorless, volatile liquid with the formula and structure . The compound is used frequently as a building block in organic chemistry as well as an industrial and chemical non ...
, CS2, may also be used. Historically, deuterated solvents were supplied with a small amount (typically 0.1%) of
tetramethylsilane Tetramethylsilane (abbreviated as TMS) is the organosilicon compound with the formula Si(CH3)4. It is the simplest tetraorganosilane. Like all silanes, the TMS framework is tetrahedral. TMS is a building block in organometallic chemistry but also ...
(TMS) as an
internal standard An internal standard in analytical chemistry is a chemical substance that is added in a constant amount to samples, the blank and calibration standards in a chemical analysis. This substance can then be used for calibration by plotting the ratio of ...
for referencing the
chemical shift In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of ...
s of each analyte proton. TMS is a
tetrahedral In geometry, a tetrahedron (plural: tetrahedra or tetrahedrons), also known as a triangular pyramid, is a polyhedron composed of four triangular faces, six straight edges, and four vertex corners. The tetrahedron is the simplest of all the o ...
molecule, with all protons being chemically equivalent, giving one single signal, used to define a chemical shift = 0 ppm. It is volatile, making sample recovery easy as well. Modern spectrometers are able to reference spectra based on the residual proton in the solvent (e.g. the CHCl3, 0.01% in 99.99% CDCl3). Deuterated solvents are now commonly supplied without TMS. Deuterated solvents permit the use of deuterium frequency-field lock (also known as deuterium lock or field lock) to offset the effect of the natural drift of the NMR's magnetic field B_0. In order to provide deuterium lock, the NMR constantly monitors the deuterium signal resonance frequency from the solvent and makes changes to the B_0 to keep the resonance frequency constant. Additionally, the deuterium signal may be used to accurately define 0 ppm as the resonant frequency of the lock solvent and the difference between the lock solvent and 0 ppm (TMS) are well known. Proton NMR spectra of most organic compounds are characterized by
chemical shift In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of ...
s in the range +14 to -4 ppm and by
spin-spin coupling In quantum mechanics, the procedure of constructing eigenstates of total angular momentum out of eigenstates of separate angular momenta is called angular momentum coupling. For instance, the orbit and spin of a single particle can interact th ...
between protons. The integration curve for each proton reflects the abundance of the individual protons. Simple molecules have simple spectra. The spectrum of
ethyl chloride Chloroethane, commonly known as ethyl chloride, is a chemical compound with chemical formula CH3CH2Cl, once widely used in producing tetraethyllead, a gasoline additive. It is a colorless, flammable gas or refrigerated liquid with a faintly sweet ...
consists of a triplet at 1.5 ppm and a quartet at 3.5 ppm in a 3:2 ratio. The spectrum of
benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...
consists of a single peak at 7.2 ppm due to the
diamagnetic ring current An aromatic ring current is an effect observed in aromatic molecules such as benzene and naphthalene. If a magnetic field is directed perpendicular to the plane of the aromatic system, a ring current is induced in the delocalized Ļ€ electrons ...
. Together with
carbon-13 NMR Carbon-13 (C13) nuclear magnetic resonance (most commonly known as carbon-13 NMR spectroscopy or 13C NMR spectroscopy or sometimes simply referred to as carbon NMR) is the application of nuclear magnetic resonance (NMR) spectroscopy to carbon. It is ...
, proton NMR is a powerful tool for molecular structure characterization.


Chemical shifts

Chemical shift In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of ...
values, symbolized by Ī“, are not precise, but typical - they are to be therefore regarded mainly as a reference. Deviations are in Ā±0.2 ppm range, sometimes more. The exact value of chemical shift depends on molecular structure and the
solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
,
temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer. Thermometers are calibrated in various temperature scales that historically have relied o ...
,
magnetic field A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and to ...
in which the spectrum is being recorded and other neighboring
functional groups In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
. Hydrogen nuclei are sensitive to the
hybridization Hybridization (or hybridisation) may refer to: *Hybridization (biology), the process of combining different varieties of organisms to create a hybrid *Orbital hybridization, in chemistry, the mixing of atomic orbitals into new hybrid orbitals *Nu ...
of the atom to which the hydrogen atom is attached and to
electronic effect An electronic effect influences the structure, reactivity, or properties of molecule but is neither a traditional bond nor a steric effect. In organic chemistry, the term stereoelectronic effect is also used to emphasize the relation between the ...
s. Nuclei tend to be deshielded by groups which withdraw electron density. Deshielded nuclei resonate at higher Ī“ values, whereas shielded nuclei resonate at lower Ī“ values. Examples of electron withdrawing substituents are -OH, -OCOR, -OR, -NO2 and
halogen The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), astatine (At), and tennessine (Ts). In the modern IUPAC nomenclature, this group is ...
s. These cause a downfield shift of approximately 2ā€“4 ppm for H atoms on CĪ± and of less than 1ā€“2 ppm for H atoms on CĪ². CĪ± is an
aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, or ...
C atom directly bonded to the substituent in question, and CĪ² is an aliphatic C atom bonded to CĪ±.
Carbonyl group In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
s,
olefin In organic chemistry, an alkene is a hydrocarbon containing a carbonā€“carbon double bond. Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
ic fragments and
aromatic ring In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to saturat ...
s contribute ''sp2'' hybridized carbon atoms to an aliphatic chain. This causes a downfield shift of 1ā€“2 ppm at CĪ±. Note that labile protons (-OH, -NH2, -SH) have no characteristic chemical shift. However, such resonances can be identified by the disappearance of a peak when reacted with D2O, as
deuterium Deuterium (or hydrogen-2, symbol or deuterium, also known as heavy hydrogen) is one of two Stable isotope ratio, stable isotopes of hydrogen (the other being Hydrogen atom, protium, or hydrogen-1). The atomic nucleus, nucleus of a deuterium ato ...
will replace a protium atom. This method is called a D2O shake.
Acidic In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
protons may also be suppressed when a solvent containing acidic deuterium ions (e.g.
methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...
-''d''4) is used. An alternate method for identifying protons that are not attached to carbons is the
heteronuclear single quantum coherence The heteronuclear single quantum coherence or heteronuclear single quantum correlation experiment, normally abbreviated as HSQC, is used frequently in NMR spectroscopy of organic molecules and is of particular significance in the field of protein NM ...
(HSQC) experiment, which correlates protons and carbons that are one bond away from each other. A hydrogen that is not attached to a carbon can be identified because it does not have a crosspeak in the HSQC spectrum.


Signal intensity

The integrated intensities of NMR signals are, ideally, proportional to the ratio of the nuclei within the molecule. Together with chemical shift and coupling constants, the integrated intensities allow structural assignments. For mixtures, the signal intensities can be used to determine molar ratios. These considerations are valid only when sufficient time is allowed for full relaxation of the affected signals, as determined by their T1 values. A further complication arises from the difficulty of integrating signals of very different line shapes.


Spin-spin couplings

In addition to
chemical shift In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of ...
, NMR spectra allow structural assignments by virtue of spin-spin coupling (and integrated intensities). Because nuclei themselves possess a small magnetic field, they influence each other, changing the energy and hence frequency of nearby nuclei as they resonate—this is known as
spin-spin coupling In quantum mechanics, the procedure of constructing eigenstates of total angular momentum out of eigenstates of separate angular momenta is called angular momentum coupling. For instance, the orbit and spin of a single particle can interact th ...
. The most important type in basic NMR is ''scalar coupling''. This interaction between two nuclei occurs through
chemical bond A chemical bond is a lasting attraction between atoms or ions that enables the formation of molecules and crystals. The bond may result from the electrostatic force between oppositely charged ions as in ionic bonds, or through the sharing of ...
s, and can typically be seen up to three bonds away (3-J coupling), although it can occasionally be visible over four to five bonds, though these tend to be considerably weaker. The effect of scalar coupling can be understood by examination of a proton which has a signal at 1 ppm. This proton is in a hypothetical molecule where three bonds away exists another proton (in a CH-CH group for instance), the neighbouring group (a
magnetic field A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and to ...
) causes the signal at 1 ppm to split into two, with one peak being a few
hertz The hertz (symbol: Hz) is the unit of frequency in the International System of Units (SI), equivalent to one event (or cycle) per second. The hertz is an SI derived unit whose expression in terms of SI base units is sāˆ’1, meaning that on ...
higher than 1 ppm and the other peak being the same number of hertz lower than 1 ppm. These peaks each have half the area of the former singlet peak. The magnitude of this splitting (difference in frequency between peaks) is known as the
coupling constant In physics, a coupling constant or gauge coupling parameter (or, more simply, a coupling), is a number that determines the strength of the force exerted in an interaction. Originally, the coupling constant related the force acting between two ...
. A typical coupling constant value for aliphatic protons would be 7 Hz. The coupling constant is independent of magnetic field strength because it is caused by the magnetic field of another nucleus, not the spectrometer magnet. Therefore, it is quoted in
hertz The hertz (symbol: Hz) is the unit of frequency in the International System of Units (SI), equivalent to one event (or cycle) per second. The hertz is an SI derived unit whose expression in terms of SI base units is sāˆ’1, meaning that on ...
(frequency) and not ppm (
chemical shift In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of ...
). In another molecule a proton resonates at 2.5 ppm and that proton would also be split into two by the proton at 1 ppm. Because the magnitude of interaction is the same the splitting would have the same coupling constant 7 Hz apart. The spectrum would have two signals, each being a doublet. Each doublet will have the same area because both doublets are produced by one proton each. The two doublets at 1 ppm and 2.5 ppm from the fictional molecule CH-CH are now changed into CH2-CH: *The total area of the 1 ppm CH2 peak will be twice that of the 2.5 ppm CH peak. *The CH2 peak will be split into a doublet by the CH peak—with one peak at 1 ppm + 3.5 Hz and one at 1 ppm - 3.5 Hz (total splitting or coupling constant is 7 Hz). In consequence the CH peak at 2.5 ppm will be split ''twice'' by each proton from the CH2. The first proton will split the peak into two equal intensities and will go from one peak at 2.5 ppm to two peaks, one at 2.5 ppm + 3.5 Hz and the other at 2.5 ppm - 3.5 Hz—each having equal intensities. However these will be split again by the second proton. The frequencies will change accordingly: *The 2.5 ppm + 3.5 Hz signal will be split into 2.5 ppm + 7 Hz and 2.5 ppm *The 2.5 ppm - 3.5 Hz signal will be split into 2.5 ppm and 2.5 ppm - 7 Hz The net result is not a signal consisting of 4 peaks but three: one signal at 7 Hz above 2.5 ppm, two signals occur at 2.5 ppm, and a final one at 7 Hz below 2.5 ppm. The ratio of height between them is 1:2:1. This is known as a triplet and is an indicator that the proton is three-bonds from a CH2 group. This can be extended to any CHn group. When the CH2-CH group is changed to CH3-CH2, keeping the chemical shift and coupling constants identical, the following changes are observed: *The relative areas between the CH3 and CH2 subunits will be 3:2. *The CH3 is coupled to two protons into a 1:2:1 triplet around 1 ppm. *The CH2 is coupled to ''three'' protons. Something split by three identical protons takes a shape known as a quartet, each peak having relative intensities of 1:3:3:1. A peak is split by ''n'' identical protons into components whose sizes are in the ratio of the ''n''th row of
Pascal's triangle In mathematics, Pascal's triangle is a triangular array of the binomial coefficients that arises in probability theory, combinatorics, and algebra. In much of the Western world, it is named after the French mathematician Blaise Pascal, although ot ...
: Because the ''n''th row has ''n''+1 components, this type of splitting is said to follow the "''n''+1 rule": a proton with ''n'' neighbors appears as a cluster of ''n''+1 peaks. With 2-methylpropane, (CH3)3CH, as another example: the CH proton is attached to three identical methyl groups containing a total of 9 identical protons. The C-H signal in the spectrum would be split into ten peaks according to the (n + 1) rule of multiplicity. Below are NMR signals corresponding to several simple multiplets of this type. Note that the outer lines of the nonet (which are only 1/8 as high as those of the second peak) can barely be seen, giving a superficial resemblance to a septet. When a proton is coupled to two different protons, then the coupling constants are likely to be different, and instead of a triplet, a doublet of doublets will be seen. Similarly, if a proton is coupled to two other protons of one type, and a third of another type with a different, smaller coupling constant, then a triplet of doublets is seen. In the example below, the triplet coupling constant is larger than the doublet one. By convention the pattern created by the largest coupling constant is indicated first and the splitting patterns of smaller constants are named in turn. In the case below it would be erroneous to refer to the quartet of triplets as a triplet of quartets. The analysis of such multiplets (which can be much more complicated than the ones shown here) provides important clues to the structure of the molecule being studied. The simple rules for the spin-spin splitting of NMR signals described above apply only if the chemical shifts of the coupling partners are substantially larger than the coupling constant between them. Otherwise there may be more peaks, and the intensities of the individual peaks will be distorted (second-order effects).


Hetero-nuclear coupling

If there are other NMR-active nuclei present in a molecule, spin-spin coupling will be observed between the hetero-atoms and the protons. This occurs most frequently in compounds that contain phosphorus or fluorine, as they are both spin 1/2 nuclei of 100% abundance. For example, the 1H signals for the protons in
fluoromethane Fluoromethane, also known as methyl fluoride, Freon 41, Halocarbon-41 and HFC-41, is a non-toxic, liquefiable, and flammable gas at standard temperature and pressure. It is made of carbon, hydrogen, and fluorine. The name stems from the fact that ...
are split into a doublet by the fluorine atom; conversely the fluorine-19 NMR spectrum of this compound shows a quartet due to being split by the three protons. Typical 2J coupling constants between fluorine and protons are 48 Hz or so; the strength of coupling declines to 2 Hz in 4J coupling. Even larger coupling constants may be seen in phosphines, especially if the proton is directly bonded to the phosphorus. Coupling constants for these protons are often as large as 200 Hz, for example in diethylphosphine, where the 1J P-H coupling constant is 190 Hz. These coupling constants are so large that they may span distances in excess of 1ppm (depending on the spectrometer), making them prone to overlapping with other proton signals in the molecule.


Carbon satellites and spinning sidebands

Occasionally, small peaks can be seen shouldering the main 1H NMR peaks. These peaks are not the result of proton-proton coupling, but result from the coupling of 1H atoms to an adjoining
carbon-13 Carbon-13 (13C) is a natural, stable isotope of carbon with a nucleus containing six protons and seven neutrons. As one of the environmental isotopes, it makes up about 1.1% of all natural carbon on Earth. Detection by mass spectrometry A mass ...
(13C) atom. These small peaks are known as carbon satellites as they are small and appear around the main 1H peak i.e.
satellite A satellite or artificial satellite is an object intentionally placed into orbit in outer space. Except for passive satellites, most satellites have an electricity generation system for equipment on board, such as solar panels or radioisotope ...
(around) to them. Carbon satellites are small because only very few of the molecules in the sample have that carbon as the rare NMR-active 13C isotope. As always for coupling due to a single spin-1/2 nucleus, the signal splitting for the H attached to the 13C is a doublet. The H attached to the more abundant 12C is not split, so it is a large singlet. The net result is a pair of evenly spaced small signals around the main one. If the H signal would already be split due to Hā€“H coupling or other effects, each of the satellites would also reflect this coupling as well (as usual for complex splitting patterns due to dissimilar coupling partners). Other NMR-active nuclei can also cause these satellites, but carbon is most common culprit in the proton NMR spectra of organic compounds. Sometimes other peaks can be seen around 1H peaks, known as spinning sidebands and are related to the rate of spin of an
NMR tube An NMR tube is a thin glass walled tube used to contain samples in nuclear magnetic resonance spectroscopy. Typically NMR tubes come in 5 mm diameters but 10 mm and 3 mm samples are known. It is important that the tubes are uniforml ...
. These are experimental artifacts from the spectroscopic analysis itself, not an intrinsic feature of the spectrum of the chemical and not even specifically related to the chemical or its structure. Carbon satellites and spinning sidebands should not be confused with impurity peaks.


See also

*
Mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...
*
Pople Notation The Pople notation is named after the Nobel laureate John Pople and is a simple method of presenting second-order spin coupling systems in NMR. The notation labels each (NMR active) nucleus with a letter of the alphabet. The difference in chemic ...
– letter designations for coupled spin-systems *
Nuclear magnetic resonance spectroscopy of proteins Nuclear magnetic resonance spectroscopy of proteins (usually abbreviated protein NMR) is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and ...


References


External links


1H-NMR Interpretation Tutorial