CH437 CLASS 8
NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 2
Synopsis. Chemical shifts - origin and theory, references. 1H and 13C chemical shifts – range, nature and causes, including electronegativity and magnetic anisotropy.
The Origin of Chemical Shift: Nuclear Spins and Local Magnetic Environment
The chemical shift is a result of the magnetic screening that is inevitably provided by electrons during an NMR experiment. A nucleus experiences not the applied magnetic field (Bo) but rather the field that has been modified by the screening (or shielding) of electrons surrounding the nucleus.
Consider s-electrons around a proton. They have spherical symmetry and circulate in the applied field, producing a magnetic field that opposes the applied field. This means that the applied field strength must be increased for the nucleus to absorb at its transition frequency. This upfield shift is also termed diamagnetic shift.
The net field, Bnuc, experienced by the nucleus is given by Lenz’s law:
Bnuc = Bo - Bo = Bo(1- ) (1)
The factor is called the shielding factor and is ~ 10-5 for 1H and < 10-3 for most other nuclei. It is properly defined in terms of three principal components (for three mutually perpendicular axes through the molecule), but in many cases, molecular symmetry allows the components to be expressed as and . Chemical shielding anisotropy (see later) is then defined as - .
Alternatively, second-order perturbation theory describes chemical shielding as the sum of two terms; D and P. The first (D) is a positive first-order term that can be calculated from ground electronic states: it is called the diamagnetic term. The second (P) is a negative second-order term that requires knowledge of wave functions of excited states. It is called the (temperature-independent) paramagnetic term.
The diamagnetic term, although small, dominates the shielding of 1H nuclei, but for nearly all other nuclei (those with p or d electrons), the paramagnetic term is dominant. The maximum value of D is ~ 20 x 10-6 (20 ppm), whereas P can be as large as 10,000 ppm for certain nuclei. This explains why the 1H effective chemical shift range is short (~20 ppm), compared with those of nuclei such as 13C (~200 ppm) and 15N (~1000 ppm).
Chemical Shift Scales
NMR data is measured in frequency units (Hz) from a chosen reference (internal or external). However, the use of frequency units in the reporting of spectra has the disadvantage that the chemical shift depends on the magnetic field strength, through the Larmor relation, = Bo/2. Hence chemical shifts are routinely reported in dimensionless units of ppm (parts per million), which is independent of either the radiofrequency field or the magnetic field.
Combining equation (1) with the Larmor expression gives
The protons that are reckoned to be shifted most upfield (i.e. are the most shielded) are those of tetramethylsilane, (CH3)4Si (TMS), which is one reason why this substance is used as a reference in 1H NMR (and also in 13C NMR).
In practice, all proton resonances are measured relative to this standard and most resonate at lower field strengths than the TMS protons (see later for an exception!), because some factor decreases the magnetic field produced by circulating electrons, relative to the protons in TMS. It will be seen later that these factors include electronegativity and magnetic fields associated with aromatic and unsaturated systems.
The same principal applies to other types of NMR, such as 13C NMR.
Chemical Shifts and the NMR Spectrum
Circulation of electrons around or close to a 1H nucleus cause an induced magnetic field that modifies the magnetic field around the nucleus as follows:
(a)If it opposes the applied field, the 1H nucleus is said to be shielded – it will resonate at higher field compared with other nuclei.
(b)If it reinforces the applied field, 1H nucleus is said to be deshielded – it will resonate at lower field compared with other nuclei.
Such shifts in the positions of NMR absorptions, arising from shielding and deshielding by electrons are called CHEMICAL SHIFTS. The direction and magnitude of chemical shift are measured with respect to the highly shielded protons of TMS: most protons in organic molecules resonate at lower field values than TMS protons, i.e. to the LEFT of the TMS signal, which is given an arbitrary value of chemical shift of 0 ppm. The same argument applies to 13C nuclei with respect to those in TMS.
The magnitude of chemical shift is expressed as (delta) in ppm, where
= (S - R) 106
Operating Frequency
The observed shifts, in Hz, are of such values that ppm is an appropriate presentation.
The relationship between low and high field (etc) with respect to the reference TMS is illustrated below.
An organic molecule normally has a number of sets of hydrogen atoms in chemically (and hence magnetically) different environments. This means that different sets of non-equivalent 1H nuclei will resonate at slightly different values of applied magnetic field strength, at constant radiofrequency (or vice-versa).
Hence it is possible to relate the number of 1H NMR signals to the number of non-equivalent hydrogen atoms (see later for explanation of non-equivalent).
Furthermore, it has been found that a proton or group of protons in a particular environment resonate at similar (but not exactly the same) chemical shifts, whatever molecule it happens (or they happen) to be part of. This very useful information has been tabulated in chemical shift tables or charts (attached).
This greatly aids the identification of unknown organic substances.
Downfield (and the less common upfield) shifts from TMS can be rationalized in structural terms that are related to the induced magnetic fields arising from circulating electrons, as described earlier.
Causes of Chemical Shift in 1H NMR Spectroscopy
Electronegativity
Highly electronegative atoms or groups attached to a carbon bearing a proton cause definite downfield effect in the chemical shift of that proton, compared with
its chemical shift in the corresponding hydrocarbon.
E.g. (with approximate values of , in ppm)
Unsaturated and Aromatic Groups: Anisotropy
Certain unsaturated groups, such as alkene, alkyne, carbonyl and aromatic groups are called anisotropic groups: their presence affects the chemical shift of nearby protons in different ways, depending the spatial relationship between the protons and the group. This is because the applied magnetic field causes local circulation of the electrons in the group, which sets up an induced magnetic field that is stronger in one direction relative to another. The anisotropy of the benzene ring and other unsaturated groups are illustrated below.
Examples of anisotropic deshielding and shielding are shown below.
Circulation charge within single bonds is less strong, but nevertheless is sufficient to give rise to the general chemical shift order methine (CH) > methylene (CH2) > methyl (CH3):
Effect of Hydrogen Bonding
Protons bonded to electronegative atoms, such as O and N, resonate at low field (high chemical shift), if there is hydrogen bonding involving the protons.
Resonance Effects
Distribution of charge (which correlates with electron density) throughout conjugated and aromatic molecules can have a distinct influence on 1H chemical shifts; protons bonded to low electron density carbons have high chemical shifts (deshielded) than those bonded to carbons with average or high electron density. The following examples serve to illustrate this.
Empirical Rules for Chemical Shift Estimation
Schoolery’s rule can be used to estimate the chemical shift of methylene protons XCH2Y, according to the nature of X and Y;
(ppm) = 0.23 + X+ Y
Values of the increments X and Y are given in Table 3-1 of the textbook. A similar rule exists for alkene protons (Tobey-Simon rules),
= 5.28 + Zgem + Zcis + Ztrans,
where the Z values are increments for particular alkenic protons, obtained from Table 3-2, and benzene ring protons, provided no two substituents are ortho to one another. Here,
= 7.27 + Si,
where Si are incremental values for protons o, m or p with respect to functional groups, as shown in Table 3-3.
13 C Chemical Shifts: Range, Nature and Causes
For reasons explained previously, the 13C chemical shift range is about ten times that of the 1H range: most 13C nuclei resonate between 0 and 230 ppm, with respect to TMS.
Sp3 Carbon Atoms
In hydrocarbons (no heteroatoms present) sp313C nuclei resonate in the range 0-60 ppm (w.r.t. TMS). The chemical shift of a carbon atom i in a hydrocarbon chain can be estimated from equation (2):
i = -2.5 + 9.1n + 9.4n - 2.5n+ 0.3n (2)
n is the number of carbon atoms directly bonded to i; n and n are the number of carbons two and three atoms removed from i, respectively. The constant –2.6 is the chemical shift of methane.
Estimates using equation (2) are often in good agreement with experimentally determined values, as illustrated for pentane, below.
If a heteroatom or polar substituent (X) is present, then its effect on 13C chemical shifts can be estimated for the functionalized carbon (-CH2X) and its three nearest neighbors, as indicated by the open values in Table 1 (attached). See the same table for increments used for >CH-X (methine) and >C-X [quaternary]. Also, if X is situated within a long carbon chain, the reference chemical shift is 29 ppm (an average value for –CH2-) and if in a cyclohexane ring, 27 ppm.
Estimates of these kinds are less reliable for more complex molecules, where there is branching or where relatively rigid ring structures are involved. In the case of branched open chain compounds, the following empirical rules may be used, illustrated for isobutane and neopentane.
Ring systems require a totally different set empirical parameters for the estimation of 13C chemical shifts. These are summarized in the table below for methyl substituents.
Stereochemistry / / / / Equatorial / 5.6 / 8.9 / 0.0 / -0.3
Axial / 1.1 / 5.2 / -5.4 / -0.1
The base chemical shift for cyclohexane is 27.7 ppm. Corrections are once more needed for branching, as follows: for two geminal -methyl groups (on the carbon of interest) the correction is –3.4; for two geminal -methyl groups the correction is –1.2. Thus estimation of the chemical shift of the C2 carbon of 1,2,3-trimethylcyclohexane is made as shown below.
For relatively rigid ring systems, gamma ()-substituents that are several bonds removed from the 13C atom of interest may, in fact, be spatially close to it if the stereochemical arrangement is gauche. In that case a correction of about –6 is needed. If the arrangement is anti, then a lower correction of about +1 is applied. For methyl substituents, these corrections are –5.4 and 0.0, respectively, reflecting the gauche stereochemistry of axial substitution and the anti stereochemistry of equatorial substitution.
Sp2 Carbon Atoms
Alkene and aromatic 13C nuclei usually resonate in the 110-160 ppm region, except in cases that involve extreme polarization of the –system.
Typical increments caused by substitution of X at C1 of ethylene are given in Table 2 and may serve as a general guide to the assignment of alkenic 13C resonances. Note that groups that increase the electron density at C2 by hyperconjugative donation (CH3 and CH2OC2H5) or lone pair donation (Cl, OCH3 and OCOCH3) cause upfield shifts in the resonance of this atom. Similarly, those substituents that reduce the electron density at C2 by electron withdrawal (CHO, COOH and COOC2H5) caused downfield shifts. These effects parallel those observed in 1H NMR spectra.
Similar effects can be seen in the spectra of monosubstituted benzenes (Table 3). Note that although highly electronegative substituents (e.g. NO2, OH, OCH3 and NH2) cause a downfield shift in C1 resonance, less electronegative and heavy substituents like Br and I are exceptional. Note also that, although increments for para carbon atoms correlate well with -electron withdrawal or lone pair electron donation, the effects of NO2 and I on ortho carbons are anomalous, because of proximity effects. 13 C chemical shifts in multi-substituted benzenes may be calculated, to a good approximation, on the assumption that the substituent effects shown in Table 3 are additive.
Chemical shifts of 13C nuclei in some common alkenic and heterocyclic systems are shown below.
Finally, carbonyl resonances appear at very low field (155-230 ppm) and are highly dependant on the nature of the carbonyl group – a fact that makes them extremely valuable in structure determination. Some examples are given below.
Note that conjugation causes an upfield shift of resonance (usually 5-25 ppm) because conjugative effects serve to increase the electron density at the carbonyl carbon. On the other hand, steric hindrance around carbonyl carbon lowers the extent of conjugation (the whole saturated system cannot be coplanar) and so causes a downfield shift in resonance.
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