nuclear magnetic resonance spectroscopy...nmr spectrometer • an nmr spectrometer is composed of: a...

Nuclear Magnetic Resonance Spectroscopy

Nuclear Spin Quantum Numbers and Allowed Nuclear Spin States

• Any atomic nucleus that has an odd mass number, an odd atomic number, or both has a spin and a resulting nuclear magnetic moment

• A nucleus with spin quantum number I has 2I + 1 spin states

Nuclear Magnetic Resonance (NMR) Spectroscopy • Spectroscopic technique that provides information about the number and

types of atoms in a molecule, such as the number and types of: • Hydrogen atoms using 1H-NMR spectroscopy• Carbon atoms using 13C-NMR spectroscopy• Phosphorus atoms using 31P-NMR spectroscopy

Origin of Nuclear Magnetic Resonance

(a) Precession of a spinning nucleus in an applied magnetic field (b) Absorption of electromagnetic radiation occurs when the frequency of radiation is equal to

the frequency of precessionResonancenuclear spin flips from a lower energy state to a higher energy state

NMR Spectrometer• An NMR spectrometer is composed of: a powerful magnet, a radio-frequency

generator, a radio-frequency detector, and a sample tube• The sample is dissolved in a solvent, most commonly CCl4, CDCl3, or D2O, and placed in a

tube, which is then suspended in the magnetic field and set spinning on its long axis

• By using a Fourier transform NMR (FT-NMR) spectrometer, a spectrum can be recorded in less than 2 seconds

1H NMR: Chemical Shift, what types of hydrogens

• Hydrogens in organic molecules are surrounded by electrons• Circulation of electron density in an applied magnetic field is called diamagnetic

current• Diamagnetic current creates a magnetic field that opposes the applied field,

referred to as diamagnetic shielding, leading to a weaker field, lower resonance frequency that can be measured, upfield shift on NMR spectra. A similar term deshielding means less shielding, a stronger field, higher resonance frequency, and downfield shift on NMR spectra.

• Chemical shift (δ) is the difference in resonance frequencies caused by differing amounts of shielding.

Diamagnetic Shielding and Chemical Shift

• Difference in resonance frequencies caused by shielding/deshielding is generally very small compared to the applied field

• Difference in resonance frequencies of hydrogens in CH3Cl compared to those in CH3F under an applied field of 7.05T is only 360 Hz, which is 1.2 parts per million (ppm) compared with the irradiating frequency

• NMR signals are measured relative to the signal of the reference compound tetramethylsilane (TMS)

• Chemical shift (d): Shift in ppm of an NMR signal refer to the signal of TMS• 1H-NMR spectrum, the signal of the 12 equivalent H atoms in TMS is set to 0• 13C-NMR spectrum, the signal of the 4 equivalent C atoms in TMS is set to 0

6 6

360 Hz 1.2 = = 1.2 ppm300 10 Hz 10´

The NMR Spectrum: Chemical Shifts

1H-NMR Spectrum of Methyl Acetate

UpfieldDownfield

Where do different types of protons absorb?

Diamagnetic Shielding

Characteristic Functional Group Chemical Shifts in 1H NMR (ppm)

Chemical Shift• Depends on the extent of shielding a particular type of hydrogen

experiences• Shielding depends on the following factors:

• Electronegativity of nearby atoms• Hybridization of adjacent atoms• Magnetic induction within an adjacent pi bond

Causes nearby nuclei to resonate farther downfield

Shielding of Acetylenic Hydrogen and Shifting of Signal Upfield by the π Bond of C≡C, weaker local magnetic field, lower frequency

Deshielding of Vinylic Hydrogens and Shifting of Signal Downfield by the π Bond of C=C, stronger local magnetic field, higher frequency

• Magnetic field induced by circulation of the p electrons in an aromatic ring deshields the hydrogens of the aromatic ring and shifts their signal downfield

• Aryl hydrogens absorb even farther downfield than vinylic hydrogens owing to the existence of a ring current

Fast Exchange

• Hydrogen atoms bonded to oxygen or nitrogen atoms can exchange faster with each other than the time it takes to acquire a 1H-NMR spectrum

• Consequences: Signals for exchanging H atoms are generally broad singlets that do not take part in splitting with other signals

• Signal will disappear if D2O or a deuterated alcohol is added to the sample• H atoms will be replaced with D atoms, which are 1H-NMR silent

• Important affected functional groups - Carboxylic acids, alcohols, amines, and amides

Chemical Equivalent Hydrogens

• Hydrogens that have the same chemical environment• Molecule with one set of equivalent hydrogens gives one NMR signal as

each H atom is in the same environment

• Molecule with two or more sets of equivalent hydrogens gives a different NMR signal for each set

• Which of the following nuclei does not show magnetic behavior?

1. 1H2. 2H3. 12C4. 13C5. 17O

• Each compound gives only one signal in its 1H-NMR spectrumPropose a structural formula for each compound

a. C2H6Ob. C3H6Cl2c. C6H12d. C4H6

• Chemically equivalent nuclei always show a single absorption

1. True2. False

• Order the following protons from lowest to highest chemical shift value

1. Ha < Hc < Hb < Hd2. Ha < Hc < Hd < Hb

3. Hc < Ha < Hd < Hb4. Hc < Ha < Hb < Hd

5. Hc < Hd < Ha < Hb

HbO

Ha

HdHc

Chemical and Stereochemical Equivalence • The following molecule has many hydrogen atoms. Let’s take a look at various pairs of

hydrogen atoms and ask: are they the same or not the same? The best way to do so is to perform a substitution test.

If the two compounds are entirely different, the groups are constitutionally inequivalent.

If the two compounds are diastereomers, the groups are diastereotopic.

If the two compounds are enantiomers, the groups are enantiotopic.

If the two compounds are identical, the groups are homotopic.

Let’s look at some examples:

• Homotopic hydrogens have identical chemical shifts under all conditions.• Enantiotopic hydrogens have identical chemical shifts in achiral

environments and different chemical shifts in chiral environments.• Diastereotopic hydrogens have different chemical shifts under all

conditions.

Stereochemistry and Topicity - Diastereotopic Groups

• Methyl groups on carbon-3 of 3-methyl-2-butanol are diastereotopic• If a H atom on one of the methyl groups on carbon-3 is substituted with a deuterium, a

new chiral center is created• Because there is already one chiral center, diastereomers are now possible• Diastereotopic hydrogens have different chemical shifts under all conditions

OH

3-Methyl-2-butanol

13

2 4

• Indicate whether the highlighted hydrogens in the following compounds are homotopic, enantiotopic, or diastereotopic

• What is the relationship between Ha and Hb in the following compound?

1. Chemically unrelated2. Homotopic3. Enantiotopic4. Diastereotopic5. None of these

ClHa

Hb

• What is the relationship between Ha and Hb in the following compound?

1. Chemically unrelated2. Homotopic3. Enantiotopic4. Diastereotopic5. None of these

Hc

HbHa

OH

1H NMR: Integration, how many hydrogens

Integrals — counting protons

Signal Areas• Modern NMR spectrometers electronically integrate and record the relative

area under each signal• Relative areas of signals are proportional to the number of equivalent hydrogens

giving rise to each signal

• Example - 1H-NMR spectrum of tert-butyl acetate

Structural Prediction• Following is a 1H-NMR spectrum for a compound of molecular formula

C9H10O2• From the integration, calculate the number of hydrogens giving rise to each signal

• 88 integration corresponds to 10 hydrogens• 44/88×10, or 5, hydrogens at δ 7.34• Similar calculations, two and three hydrogens at δ 5.08 and 2.06

• Molecular formula C7H14O

• Which of the following molecules best fits the following NMR spectrum?

1. 2. 3.

4. 5.

• Which of the following molecules best fits the following NMR spectrum?

1. 2. 3. 4. 5.O

O OH

OH

OH

OH

HO

HO

HO

HO

• Which of the following molecules best fits the following NMR spectrum?

1. 2. 3.

4. 5.

Cl OH

NH2NH2

• 1H NMR will allow one to distinguish between the following two molecules:

1. True2. False

H BrBr H

1H NMR: Signal splitting, neighbors of hydrogens

Signal Splitting and the (n + 1) Rule• Signal splitting - Splitting of an NMR signal into a set of peaks by the

influence of neighboring nonequivalent hydrogens• Peaks are named by how a signal is split

• Singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), and so forth• Degree of signal splitting can be predicted on the basis of the (n + 1) rule

• (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

1,1-Dichloroethane

Example - Predicting 1H-NMR Spectra II• Predict the number of signals and the splitting pattern of each signal in the

1H-NMR spectrum of each molecule

Origins of Signal Splitting• Spin-spin coupling: Interaction in which nuclear spins of adjacent atoms

influence each other and lead to the splitting of NMR signals• Coupling constant (J) : Separation on an NMR spectrum (in hertz)

between adjacent peaks in a multiplet• Vicinal hydrogens: H atoms on two C atoms that are bonded to each

other • Coupling between vicinal hydrogens is referred to as vicinal coupling

Spin-Spin Splitting: Why Does It Happen? Total magnetic field at H (observed) = Applied field +

effect of H (neighbor)

• These two possibilities have different energies – so there are two lines• Each is equally probable – so the intensity of the lines is equal

Illustration of Spin-Spin Coupling That Gives Rise to Signal Splitting in 1H-NMR Spectra

Shielding vs. De-shielding

Spin-Spin Splitting: The Coupling Constant

Spin-Spin Splitting: Counting Neighbors

Spin-Spin Splitting: More Than One Neighbor

Pascal’s Triangle

Signature “Splitting” Patterns in 1H NMR Spectra

Complex Splitting Patterns

Jab ≠ Jbc

(n + 1)×(m + 1) peaks, a H atom that is coupled to a set of n H atoms with one coupling constant and m H atoms with another coupling constant

Bond Rotation

• Key parameter as the angle between C—H bonds determines the extent of coupling

• In molecules with relatively free rotation about C—C sigma bonds, H atoms bonded to the same C in CH3 and CH2 groups are generally equivalent

• If there is restricted bond rotation, as in alkenes and cyclic structures, H atoms bonded to the same C may not be equivalent

• Nonequivalent 1H nuclei on the same carbon will couple and cause signal splitting (referred to as geminal coupling)

Restricted Bond Rotation

Ethyl Propenoate

2-methyl-2-vinyloxirane

300 MHz 1H-NMR Spectrum of 1-Chloro-3-Iodopropane

• The central CH2 (c) has the possibility of splitting into 3×3 = 9 peaks (a triplet of triplets)

• Only 4 + 1 = 5 peaks are distinguishable as the values of Jab and Jbc are similar • m + n + 1 peaks, instead of (n + 1)×(m + 1) peaks.

Spin-Spin Splitting: More Complex Splitting Patterns

13C NMR

13C-NMR Spectroscopy• 13C atoms in a molecule rarely have 13C next to them

• 13C—13C signal splitting is not normally observed• According to the (n + 1) rule, a 13C signal is split by the hydrogens bonded to it • Coupling constants of 100 and 250 Hz are common, which means that there is often

significant overlap among signals and splitting patterns can be difficult to determine

• The most common mode of operation of a 13C-NMR spectrometer is a hydrogen-decoupled mode

• In the hydrogen-decoupled mode, a sample is irradiated with two different radio frequencies

• First radio frequency is used to excite all 13C nuclei• Second is a broad spectrum of frequencies that causes all hydrogens in the molecule to

undergo rapid transitions among their nuclear spin states

• On the time scale of a 13C-NMR spectrum, each hydrogen is in a time average of the two states, with the result that 1H-13C spin-spin interactions are not observed

• Process is known as spin-spin decoupling

Hydrogen-Decoupled 13C-NMR Spectrum of 1-Bromobutane

Characteristic Functional Group Chemical Shifts in 13C NMR (ppm)

• Which of the following is true of 13C-NMR spectra?

1. The number of carbon atoms in a molecule can be ascertained2. The number of hydrogen atoms in a molecule can be ascertained3. Certain functional groups can be deduced from the locations of the

peaks4. Both the number of carbon atoms and the number of hydrogen

atoms in a molecule can be ascertained5. All of these

• How many signals will appear in the 13C-NMR spectrum of the following molecule?

1. 102. 113. 124. 145. 15

• How many signals will appear in the 13C-NMR spectrum of the following molecule?

1. 12. 23. 34. 45. 5

• How many signals will appear in the 13C-NMR spectrum of the following molecule?

1. 32. 43. 54. 65. 7

OCH3 N

O

CH3

O

painkiller Demerol

• Predict the number of signals in a proton-decoupled 13C-NMR spectrum of each compound

Interpreting NMR Spectra

Interpreting NMR Spectra• Alkanes

• 1H-NMR chemical shifts fall within the range of δ 0.8–1.7 • 13C-NMR chemical shifts fall within the considerably wider range of δ 10–60

• Alkenes• 1H-NMR signals appear in the range δ 4.6–5.7• Coupling constants are generally larger for trans vinylic hydrogens (11–18 Hz) when

compared with cis vinylic hydrogens (5–10 Hz)• Signal of each vinylic hydrogen in vinyl acetate is predicted to be a doublet of

doublets• 13C-NMR signals for sp2 hybridized carbons appear in the range δ 100–150 ppm,

which is considerably downfield from sp3 hybridized carbons

Vinyl Acetate

Interpreting NMR Spectra• Alcohols

• Chemical shift of a hydroxyl hydrogen in a 1H-NMR spectrum is variable and depends on the purity of the sample, the solvent, the concentration, and the temperature

• Often appears in the range δ 3.0–4.0, but may be as low as δ 0.5• Hydrogens on the carbon bearing the —OH group are deshielded by the electron-

withdrawing inductive effect of the oxygen atom and their signals appear in the range δ 3.4–4.0

1-Propanol

Interpreting NMR Spectra• Ethers

• A distinctive feature in the 1H-NMR spectra of ethers is the chemical shift of hydrogens, δ 3.3–4.0, on the carbons bonded to the ether oxygen

• Range corresponds to a downfield shift of approximately 2.4 units compared with their normal position in alkanes

• Aldehydes and ketones• Signal for aldehyde hydrogens appears between δ 9.5 and δ 10.1 in the 1H-NMR

spectrum• H atoms on a-carbons of aldehydes and ketones appear around δ 2.2 to 2.6• In 13C-NMR, carbonyl carbons have characteristic positions between δ 180 and δ 215

• Amines• In the 1H-NMR spectrum, amine hydrogens appear from δ 0.5 to 5.0 depending on

experimental conditions due to hydrogen bonding• Amine hydrogens generally appear as broad singlets• Carbons bonded to nitrogen appear in the 13C-NMR spectrum approximately 20 ppm

higher than in alkanes of comparable structure, but about 20 ppm below carbons attached to oxygen in ethers or alcohols

Interpreting NMR Spectra• Carboxylic acids and esters

• Signals for hydrogens on the α-carbon to a carboxyl group in acids and esters appear in a 1H-NMR spectrum in the range δ 2.0 to 2.6

• Hydrogen of a carboxyl group gives a very distinctive signal in the range δ 10 to 13• 13C resonance of the carboxyl carbon in acids and esters appears in the range δ 165

to 185 • Hydrogens α to an ester oxygen are strongly deshielded and resonate between δ 3.7 and

4.7

2-Methylpropanoic Acid (Isobutyric Acid)

• Which of the following molecules best fits the following 13C-NMR data?

• 13C-NMR data: 20, 22, 32, 44, and 67 ppm

1. 2.

3. 4.

HO

H3C

CH3 HO

H3C

CH3

HO

H3C CH3

HO

H3CCH3

• Molecular formula C5H10O

Spectral Problem

• Molecular formula C7H14O

Spectral Problem

• Following is the 1H-NMR spectrum of compound O, molecular formula C7H12

• Compound O reacts with bromine in carbon tetrachloride to give a compound with the molecular formula C7H12Br2

• The 13C-NMR spectrum of compound O shows signals at d 150.12, 106.43, 35.44, 28.36, and 26.36

• Deduce the structural formula of O

Spectral Problem