Chapter 16Nuclear Magnetic Resonance

Spectroscopy

The Spinning Proton

A spinning proton generates a magnetic field, resembling that of a small bar magnet.

An odd number of protons in the nucleus creates a net nuclear spin.

The nuclear spin will generates a small magnetic field called the magnetic moment.

Applying an External Field

An external magnetic field (B0) applies a force to a small bar magnet.

The bar magnet aligns with the external field.

In the absence of an applied magnetic field nuclei do not align their nuclear spins.

In an applied magnetic field nuclei orient their nuclear spins either parallel or antiparallel to the applied field. The parallel orientation is more stable.

Nuclear Spins in a Magnetic Field

Nuclear Spins in a Magnetic Field

Influence of a Radio frequency Pulse

The principle behind NMR is that many nuclei have spin.

If an external magnetic field is applied, an energy transfer is possible between the base energy to a higher energy level.

The energy transfer takes place at a wavelength (the resonance frequency) that corresponds to the radio frequency region.

When the spin returns to its base level, energy is emitted at the same frequency.

The signal that matches this transfer is measured in many ways and processed in order to yield an NMR spectrum for the nucleus concerned.

tetramethylsilane (internal standard)

Common NMR Solvents

Proton NMR Spectrum of Methanol

The more shielded methyl protons appear toward the right of the spectrum.

The less shielded hydroxyl proton appears toward the left (lower field).

In an NMR spectrum the magnetic field increases from left to right.Signals on the right side of the spectrum are said to be upfield and

those on the left are said to be downfield.

Resonance Frequency

Protons are shielded by valence electrons surrounding them which circulate in an applied magnetic field producing a local diamagnetic current in the

opposite direction.

This diamagnetic “shielding” will affect the frequency of radiation necessary to cause a nucleus to spin flip (the resonance frequency).

The Induced Magnetic Field

Nuclei will absorb radiation of slightly different frequency depending upon their local magnetic environments.

Applied Magnetic Field (B0)

Ener

gy

1.41 tesla

7.04 tesla

14.09 tesla

60 MHz 300 MHz 600 MHz

The energy difference between the parallel orientation of a nuclear spin in a magnetic field and the antiparallel orientation of the spin in the field is proportional to the strength of the applied magnetic field.

Energy vs Field Strength

Diagram of an NMR Spectrometer

An NMR spectrometer is an instrument which measures the applied magnetic field strengths required to produce a certain energy difference between nuclear spins of various atoms in a molecule oriented parallel and antiparallel to the applied magnetic field.

Continuous wave NMR spectrometers are similar in principle to optical spectrometers.

The sample is held in a strong magnetic field, and the frequency of the source is slowly scanned

or

The source frequency is held constant, and the field is scanned.

Continuous Wave (CW) NMR Instruments

In FT-NMR, all frequencies in a spectrum are irradiated simultaneously with a radio frequency pulse. A single oscillator

(transmitter) is used to generate a pulse of electromagnetic radiation of frequency.

Following the pulse, the nuclei return to equilibrium. A time domain emission signal (called a free induction decay (FID)) is

recorded by the instrument as the nuclei relax back to equilibrium. A frequency domain spectrum is then obtained by

Fourier transformation of the FID.

Fourier Transform (FT) NMR instruments

Characteristics of NMR Spectra

Location of Signals (“Chemical Shift”)

Area of Signals (Integration)

Shape of Signals (Splitting)

Identifying Magnetically Equivalent Protons(which “resonate” at identical frequencies)

C CHH

H HH H

C CHH

H HH X

Replace H withanother group

C CHH

H XH H

Replace H withanother group

? Identical !!

Homotopic ProtonsProtons that are interchangeable by rotational symmetry

The protons are homotopic !!

Enantiotopic ProtonsProtons that are not interchangeable by rotational

symmetry, but are interchangeable by reflectional symmetry.

? Enantiomers !!

The protons are enantiotopic !!

Replace H withanother group

C CCH3H3C

H XH H

C CCH3H3C

H HH H

Replace H withanother group

C CCH3H3C

H HH X

Homotopic and Enantiotopic Protons are

Magnetically Equivalent

methyl acetate

Homotopic Protons

H3CC

O

CH3H3C

C

O

CO

O

CH2H2C

H2CCH2

CH2

CH2

CH3H3C

H

H H

H

H3CC

O

HH3CCO

OCH3

Homotopic vs Enantiotopic

NH

HCH2C OO

H

glycine NH

HCH2C OOH

There are three magnetically distinct types of protons in the molecule.

NHa

HaCC OOHc

Hb Hb The Ha protons are magnetically equivalent and homotopic.

The Hb protons are magnetically equivalent and enantiotopic.

Homotopic vs Enantiotopic

ethyl acetateCH3

CO

CH2CH3

O

CH3C

OCH2

CH3

O

There are three magnetically distinct types of protons in the molecule.

CC

OC

C

OHa

Ha Ha

Hb HbHc

Hc Hc

The Ha protons are magnetically equivalent and homotopic.

The Hb protons are magnetically equivalent and enantiotopic.

The Hc protons are magnetically equivalent and homotopic.

? Diastereomers !!

The protons are diastereotopic !!

Diastereotopic ProtonsNonequivalent protons which produce diastereomers

through the replacement test.

C CCH3HO

H HH3C H

Replace H withanother group C C

CH3HO

H HH3C X

Replace H withanother group

C CCH3HO

H XH3C H

*

*

*

? Diastereomers !!

The protons are diastereotopic !!

Diastereotopic ProtonsNonequivalent protons which produce diastereomers

through the replacement test.

C CH

H

H

H3C

Replace H withanother group

C CX

H

H

H3C

Replace H withanother group

C CH

X

H

H3C

Diastereotopic Protons are

Magnetically NONequivalent

Diastereotopic protons are usually single protons in magnetically and chemically distinct environments in

molecules which already possess a chiral center.

Are all the protons in cyclohexane magnetically really equivalent?

How many magnetically different sets of protons does the following molecule contain?

N

CH3

C

O

H

CH2HO

OHN

CH3

C

O

H

CH2HO

OH

H

pyridoxal

enantiotopic

homotopic

How many magnetically different sets of protons does the following molecule contain?

O2C CO2

HO

O2C

H

H

H H

isocitrate diastereotopic

How many magnetically different sets of protons does the following molecule contain?

CH3

C

O

CHCH2

CH3

CH2CH3

CH3

C

O

CHCH2

CH3

CH2CH3

H

H

H H

DEET

homotopic

homotopichomotopic

How many magnetically different sets of protons does the following molecule contain?

O

O

O

N

H

F

paroxetine

O

O

O

N

H

F

H

HH H

H H

H

HH

H

H

HH

H

H

HH

H

H

Chemical Shifts

Chemical Shifts

DOWNFIELD UPFIELDDESHIELDED SHIELDEDELECTRON-POOR ELECTRON-RICHHIGHER FREQUENCY LOWER FREQUENCY

NMR Delta (δ) Scale

Typical Chemical Shift Values

Inductive Effects on Chemical Shift

H C

H

H

H H C

H

H

I H C

H

H

Br H C

H

H

Cl H C

H

H

F

δ 1.0 2.2 2.7 3.1 4.4 ppm

H C

H

H

H H C

H

H

Cl H C

Cl

H

Cl H C

Cl

Cl

Cl

δ 1.0 3.1 5.3 7.3 ppm

Anisotropic Effects

Magnetic Fields Around Aromatic Rings

The induced magnetic field of the circulating aromatic electrons opposes the applied magnetic field along the axis of the ring.

δ7.2

The aromatic hydrogens are on the equator of the ring, where induced field lines curve around and reinforce the applied field.

Protons in the region where the induced field reinforces the applied field are deshielded and will appear at lower fields in the spectrum (to the left).

Magnetic Fields Around Aromatic Rings

δ 0.3

Magnetic Field of Alkenes

The pi electrons of the double bond generate a magnetic field that opposes the applied magnetic field in the middle of the molecule but reinforces the applied

field on the outside where the vinylic protons are.

This reinforcement will deshield the vinylic protons making them shift downfield in the spectrum to the range of 5 - 6 ppm.

δ5.5

Vinyl protons are positioned on the periphery of the induced magnetic field of pi electrons. In this position, they are deshielded by the induced magnetic field.

Magnetic Fields of Alkynes

The acetylenic protons are in the axis of the generated field.

Since the generated magnetic field opposes the applied field, the acetylenic protons are shielded and will be found at higher fields than vinylic protons.

δ2.5

When the acetylenic triple bond is aligned with the magnetic field, the cylinder of electrons circulates to create an induced magnetic field.

The acetylenic proton lies along the axis of this field, which opposes the external field.

Typical Chemical Shift Values

Integration

Methyl t-Butyl Ether

4-Hydroxy-4-methyl-2-pentanone