Application of Nuclear Magnetic Resonance (NMR) Spectroscopy
Arguably the most powerful and broadly applicable technique for structure determination available to organic chemists. In most cases, the structure of a compound can be determined using only NMR spectroscopy
Nuclear Magnetic Resonance (NMR) Spectroscopy
Involves the study of the interaction between electromagnetic radiation and the nuclei of atoms.
Nuclear Spin
A nucleus with an odd number of protons and/or an odd number of neutrons possesses a quantum mechanical property called
nuclear spin
, and it can be probed by an NMR spectrometer
Magnetic Moment
A spinning proton(nuclear spin) can be viewed as a rotating sphere of charge, which generates a magnetic field, called a
magnetic moment
, which is similar to the magnetic field produced by a bar magnet
Nuclei Not Possessing Magnetic Moment
The nucleus of a 12C atom has an even number of protons and neutrons and therefore does not possess magnetic moment.
Alpha and Beta Spin States
When the nucleus of a hydrogen atom (a proton) is subjected to an external magnetic field, the interaction between the magnetic moment and the magnetic field is quantized, and the magnetic moment must align either with the field or against the field. A pr
Quantifiable Energy Difference for Spin States
The two spin states are not equivalent in energy, and there is a quantifiable difference in energy (?E) between them
Nuclear Magnetic Resonance
When a nucleus occupying the alpha spin state is subjected to electromagnetic radiation, an absorption can take place if the energy of the photon is equivalent to the energy gap between the spin states. The absorption causes the nucleus to flip to the bet
Radio Frequency Radiation
When a strong magnetic field is employed, the frequency of radiation typically required for nuclear resonance falls in the radio wave region of the electromagnetic spectrum, called the
radio frequency (rf) radiation
Diamagnetism
The effect that In the presence of an external magnetic field, the electron density circulates, producing a local (induced) magnetic field that opposes the external magnetic field. All materials possess diamagnetic properties, because all materials contai
Electron Shielding of Protons
When electron density circulates around a proton as a result of an external magnetic field, the proton becomes subject to the strong, external magnetic field and the weak induced magnetic field established by the circulating electron density. The proton t
Electron Deshielding of Protons
Some protons are surrounded by more electron density and are more shielded, while other protons are surrounded by less electrons are and less shielded, or
deshielded
. As a result, protons in different electronic environments will exhibit a different ener
Magnetic Field Strength
The magnetic field establishes and energy gap (?E) between spin states, which enables the nuclei to absorb rf radiation. The magnitude of this energy gap depends on the strength of the imposed external magnetic field.
The magnetic gap increases with incre
Fourier-Transform NMR (FT-NMR)
in an FT-NMR spectrometer, the sample is irradiated with a short pulse that covers the entire range of relevant rf frequencies. All protons are excited simultaneously and then begin to return(or decay) to their original spin states. As each type of proton
Deuterated Solvetns
If the solvent in an FT-NMR has protons, the spectrum will be overwhelmed with signals from the solvent, rendering it unreadable. Deuterated solvents are generally used. They also resonate but at a different frequency than protons and so are invisible to
1H NMR Spectrum
The spectrum produced by 1H NMR spectroscopy (shown in image) is generally rich with information that can be interpreted to determine molecular structure.
3 Important Characteristics of NMR Signals
1. The
location
of each signal indicates the electronic environment of the protons giving rise to the signal...
2. The
area
under each signal indicates the number of protons giving rise to the signal...
3. The
shape
of the signal indicates the number of n
Number of Signals in NMR Spectrum
The number of signals in the 1H NMR spectrum shown indicates the number of different kinds of protons(protons in different electronic environments)
Chemical Equivalence
Protons that occupy identical electronic environments are called
chemically equivalent
, and they will produce only one signal. Two electrons are chemically equivalent if they can be interchanged via a symmetry operation - either rotation or reflection
Homotopic
The two protons on the middle carbon of propane are interchangeable by rotational symmetry(1st example in image) are therefore said to be
homotopic
. Homotopic protons are chemically equivalent
Replacement Test
Draw the compound two times, each time replacing one of the protons with deuterium. Then, determine the relationship between the two drawings
Replacement Test Results for Homotopic Molecules
If after the replacement test, the two drawings represent the same compound, then the protons are homotopic
Enantiotopic
When protons are interchangeable by reflectional symmetry(have plane of symmetry), they are said to be enantiotopic and are chemically equivalent in the achiral environment of an NMR experiment
Replacement Test Results for Enantiotopic Molecules
If after the replacement test, the two drawings represent enantiomers, then the protons are enantiotopic
Determining Chemical Equivalence
First determine if there is an axis of symmetry that interchanges the protons. If there is, then the protons are homotopic, whether or not there is a plane of symmetry. If the protons cannot be interchanged by rotation, then look for reflectional symmetry
Diastereotopic
When protons are neither homotopic nor enantiotopic, they are said to by
diastereotopic
and are not chemically equivalent because they cannot be interchanged by symmetry
Replacement Test Results for Diastereotopic Molecules
If after the replacement test, the two drawings represent diasteromers, then the protons are diastereotopic
Predicting The Number of Signals in H1 NMR Spectrum of a Compound
In general, it is possible to determine the number of expected signals for a compound using a few simple rules
1st Rule for Predicting the Number of Signals in H1 NMR Spectrum
The three protons of a CH3 group are always chemically equivalent
2nd Rule for Predicting the Number of Signals in H1 NMR Spectrum
The two protons of a CH2 group will generally be chemically equivalent if the compound has no chirality centers. If the compound has a chirality center, then the protons of a CH2 group will generally not be chemically equivalent
3rd Rule for Predicting the Number of Signals in H1 NMR Spectrum
Two CH2 groups will be equivalent to each other (giving 4 equivalent protons) if the CH2 groups can be interchanged by either rotation or reflection
H1 NMR Spectrum of Cyclohexane Chair Conformation
Axial protons occupy different electronic environments than equatorial ones so they are not chemically equivalent. We would expect 2 signals in the 1H NMR spectrum of cyclohexane but it only exhibits one because at room temperature the ring is flipping be
Variable-Temperature NMR
By varying the temperature, it is possible to measure the rates and activation energies of many rapid processes. For example, if a sample of cyclohexane is cooled to -100�C, ring flipping occurs at a very slow rate and separate signals are in observed for
Chemical Shift (?)
The location of a signal in an NMR spectrum is called its
chemical shift (?)
*, which is defined relative to the frequency of absorption of a reference compound, tetramethylsilane (TMS)(shown in image)
Calculating Chemical Shift
The frequency of each signal is described as the difference (in hertz) between the resonance frequency of the proton being observed and that of TMS divided by the operating frequency of the spectrometer
Upfield and Downfield Signals
The left side of an NMR spectrum is described as
downfield
, and the right side of the spectrum is described as
upfield
Downfields Signals
Signals on the left side of the spectrum (downfield) are "high-frequency signals" because they result from deshielded protons that absorb higher frequencies of rf radiaition
Upfield Signals
Signals on the right side of the spectrum (upfield) are "low-frequency signals" because they result from shielded protons that absorb lower frequencies of rf radiation
Inductive Effects of NMR Spectrum
Electronegative atoms, such as halogens, withdraw electron density from neighboring atoms(1st example in image). This inductive effect causes the protons of the methyl group to be deshielded(surrounded by less electron density), and as a result, the signa
Electronegativity of Atom and Chemical Shift on NMR Spectrum
The strength of this effect depends on the electronegativity of the halogen. Fluorine is the most electronegative element and therefore produces the strongest effect
Additive Effect of Halogens and Chemical Shift
When multiple halogens are present, the effect is additive
Inductive Effects and Distance
The inductive effect tapers off drastically with distance. The effect is most significant for the protons at the alpha positiion. Beta position protons are slightly affected, and protons at the gamma position are virtually unaffected
Benchmark Values for Chemical Shifts for NMR Spectrum
These are the expected chemical shifts for protons that lack neighboring electronegative atoms. In the absence of inductive effects, a methyl group(CH3) will produce a signal near 0.9 ppm, a
methylene group
(CH2) will produce a signal near 1.2 ppm, and a
Effect of a Few Functional Groups on the Chemical Shifts of Alpha Protons
Diamagnetic Anisotropy
The chemical shift of a proton is also sensitive to diamagnetic effects that result from the motion of nearby pi bond electrons. When a benzene is placed in a strong magnetic field, the pi electrons circulate, and this flow of electrons creates an induced
Diamagnetic Anisotropy
Means that different regions of space are characterized by different magnetic field strengths. The protons connected to the outside of the benzene ring experience the external magnetic field plus the local magnetic field and they experience a stronger mag
Chemical Shifts for Protons in Different Electronic Environments
Integration of NMR Spectrum Signals
The area under each signal which indicates the number of protons giving rise to the signal. The computer calculates and displays this area as a numerical value placed above or below the signal.
Finding the Relative Number of Protons Producing Signal
The area of each signal provided by the computer can be converted to useful information by choosing the smallest number and then dividing all integration values by this number and then, if necessary, multiplying each value by some value to obtain whole nu
Multiplicity
Defined by the number of peaks in the signal. A
singlet
has one peak, a
doublet
has two peaks, a
triplet
has three peaks, a
quartet
has four peaks, a
quintlet
has five peaks, and so on
Signal Multiplicity
If Ha and Hb are not equivalent to each other, they will produce different signals. A signal's multiplicity is the result of the magnetic effects of neighboring protons and therefore indicates the number of neighboring protons. In this image, Hb has a mag
The Process of Spin-Spin Splitting or Coupling
In some molecules, Hb will be aligned with the field, while in other molecules, Hb will be aligned against the field. As a result, the chemical shift of Ha in some molecules will be slightly different than the chemical shift of Ha in other molecules, resu
Result of Spin-Spin Splitting in NMR Spectru-
In other words, the presence of Hb splits the signal for Ha into a doublet. Ha has the same effect on the signal of Hb into a doublet. This phenomenon is called
spin-spin splitting
, or
coupling
Triplet Signal
Consider a scenario in which Ha has two neighboring protons(1st example in image). The chemical shift of Ha is impacted by the presence of both Hb protons, each of which can be aligned either with or against the external field. In each molecule, Ha can fi
Quartet Signal
Consider a scenario in which Ha has three neighbors(1st example in image). The chemical shift of Ha is impacted by the presence of all three Hb protons, each of which can be aligned either with the field or against the field. Ha can find itself in one or
Multiplicity Indicates the Number of Neighboring Protons
n + 1 Rule
If n is the number of neighboring protons, then the multiplicity will be n + 1. Extending this rule, a proton with six protons or six neighbors (n=6) will be split into a septet (7 peaks, or n+1). This rule applies only when all of the neighboring protons
Chemical Equivalence and Splitting
Equivalent protons do not split each other. In this image, all four protons are chemically equivalent and do not split each other. The neighboring protons must be different than the protons producing the signal for splitting to occur
When Splitting is Commonly Observed
Splitting is most commonly observed when protons are separated by either two or three sigma bonds; that is, when the protons are either diastereotopic protons on the same carbon atom(geminal) or connected to adjacent carbon atoms(vicinal). When two proton
Coupling Constant or J value
When signal splitting occurs, the distance between the individuals peaks of a signal is called the
coupling constant
, or
J value
, and is measured in hertz. Neighboring protons always split each other with equivalent J values
Recognizing Ethyl Groups on NMR Spectrum
A compound containing an isolated ethyl group(isolated means that the CH2 protons are only being split by the CH3 protons) will display a triplet with an integration of 3, upfield from a quartet with an integration of 2 in its 1H NMR spectrum
Recognizing when J values are Different
Since the two kinds of protons of an ethyl group are splitting each other, the J values for the triplet and quartet must be equivalent. In this image, the quartet has a larger J value than the triplet, so these two signals are not splitting each toerh
Recognizing Isopropyl Groups on NMR Spectrum
A compound containing an isolated isopropyl group will display a doublet with an integration of 6, upfield from a septet (seven peaks) with an integration of 1. A septet is usually hard to see, so an enlarged reproduction (inset) of the signal is often di
Recognizing tert-butyl Groups on NMR Spectrum
A compound containing a tert-butyl group will display a singlet with a relative integration of 9
Characteristic Splitting Patterns for Ethyl, Isopropyl, and tert-Butyl Groups
Complex Splitting
Complex splitting occurs when a proton has two different kinds of neighboring protons. Often, several peaks will overlap, producing a signal that requires a more detailed analysis and is called a multiplet
The 1H NMR Spectrum of Ethanol
In this addition, the spectrum exhibits the characteristic signals of an ethyl group. In addition, another signal is observed at 2.2 ppm, representing the hydroxyl group(OH)
NMR Signals for Hydroxyl Groups
Hydroxyl protons typically produce a signal between 2 and 5 ppm, and it is often difficult to predict exactly where that signal will appear. Generally, no splitting is observed across the oxygen atom of an alcohol, because proton exchange is very rapid pr
Labile
Hydroxyl protons are said to be
labile
, because of the rapid rate at which they are exchanged. This proton transfer process occurs at a faster rate than the timescale of an NMR spectrometer, producing a blurring effect that averages out any possible spli
NMR Signals for Aldehydes
Aldehydic protons, which generally produce signals near 10 pp, will often couple only weakly with their neighbors(a very small J value) and splitting may or may not be noticeable
Using 1H NMR Spectroscopy to Distinguish between Compounds
NMR spectroscopy is a powerful tool for distinguishing compounds from each other. Consider the three constitutional isomers in this image, which produce different numbers of signals in their 1H NMR spectra. Even compounds that produce the same number of s
1st Step in Analyzing a 1H NMR Spectrum
Always begin by inspecting the molecular formula(if it is given), as it the hydrogen deficiency index(HDI) which provides useful clues about the structure of the compound
Using HDI of a Compound to Determine Compound Structure
An HDI of 0 indicates that the compound does not possess any rings or pi bonds. An HDI of 1 indicates that the compound has either 1 ring or 1 pi bond. An HDI of 4 or more should indicate the possible presence of an aromatic ring
2nd Step in Analyzing a 1H NMR Spectrum
Consider the number of signals and integration of each signal(gives clues about symmetry of the compound)
3rd Step in Analyzing a 1H NMR Spectrum
Analyze each signal(chemical shift, integration, and multiplicity) and then draw fragments consistent with each signal. These fragments become our puzzle pieces that must be assembled to produce a molecule structure
4th Step in Analyzing a 1H NMR Spectrum
Assemble the fragments into a molecular structure
Acquiring a 13C NMR Spectrum
In 13C spectroscopy, only the chemical shift is generally reported.
Broadband Decoupling
The splitting patterns of 13C is very complex and the signals overlap to produce an unreadable spectrum. To solve this problem, all 13C-1H splitting is suppressed by a technique called
broadband decoupling
, which uses two rf transmitters. The 1st transmi
Off-Resonance Decoupling
With this technique, only the one-bond couplings are observed, so CH3 groups appear as quartets, CH2 groups appear as triplets, CH groups appear as doublets, and quaternary carbon atoms appear as singlets
Symmetry and Number of Signals in 13C NMR Spectroscopy
The number of signals in a 13C NMR spectrum represents the number of carbon atoms in different electronic environments(not interchangeable by symmetry). Carbon atoms that are interchangeable by a symmetry operation(either rotation or reflection) will only
Chemical Shifts in 13C NMR Spectroscopy
The location of each signal is dependent on shielding and deshielding effects, just as we saw in 1H NMR Spectroscopy
DEPT 13C NMR Spectroscopy
This technique is called distortion enhancement by polarization transfer (DEPT). This technique allows us to identify whether each signal is either a CH3 group, a CH2 group, a CH group, or a quaternary carbon atom