Nuclear Magnetic Resonance Spectroscopy for Organic Chemistry

 

NMR Overview

As you work your way through the provided theory refer to the definitions pages!!

 

NMR only works for nuclei that have the quantum mechanical property of SPIN! Spin exists for nuclei with odd atomic mass.

 

The spin properties of nuclei characterize each nucleus according to a physical parameter called the chemical shift.

 

For a given molecule, coupling constants and relaxation times give information about the connectivity between atoms.

 

NMR can be used to follow chemical reactions.

 

NMR samples can be solid, liquid, or gas.

 

NMR can be used to analyze mixtures.

 

Sample quantities should be in the micro- to milligram range.

 

Proton NMR

 

What information can you obtain from a proton NMR spectrum of a compound?

 

-How many different kinds of hydrogen are present (-CH, -CH2, -CH3).

-Environment of the hydrogen atoms.

-Relative number of hydrogen atoms.

-Which hydrogen atoms are 2- or 3-bond neighbors.

 

The Basics of NMR Theory

 

-An electron may be in a position of spin up or spin down.

 

-In a general chemistry course, you may have constructed spectrometers to view the quantum steps of electrons moving from one energy level to another.  These steps were observed as emissions of light, of a given frequency, resulting in characteristic color observed for the transition.

 

-Protons, like electrons, can also be in a position of spin up or spin down for certain nuclei.

 

-In Organic spectroscopy, you view the quantum jumps of protons that possess the property of spin as they switch from spin up to spin down.

 

-What we are able to observe is the absorption of energy that results from a proton switching from a spin of + ½ to a spin of – ½.

 

What follows are the details of this phenomenon!

Details Synonymous with TheoryJ

 

Magnetic Moment (μ)

 

-The magnetic field generated by a spinning nucleus with a positive charge.

 

Spin Quantum Number (I)

 

-The value assigned to spinning nuclei.

 

-Nuclei that possess spin must have either:

 

a.)              Odd mass – I = ½

These nuclei have a spherical shape.

Can you think of any?

 

 

1H, 13C, 15N, 19F, 29S, and 31P

b.)              Odd atomic number – I = 1, 3/2, 2, 5/2, …(increments of ½)

2H, 11B, 14N, 17O, 33S, and 35Cl

 

These nuclei have non-spherical or elliptical shape they are referred to as quadrupolar.

 

Quadrupolar nuclei have a spin of one or more.

 

c.)              What type of nuclei have no spin?  I = 0

 

12C and 18O

 

For Nuclei with a Spin of ½

 

The RIGHT-HAND-RULE gives the direction of the spin of the nucleus.  If the nucleus is aligned with the magnetic field, what direction will the nucleus spin?  I = ____?

 

If the nucleus is oriented opposite the magnetic field, what direction will it spin?  I = ____?

 

How does the magnetic moment (μ) of a nucleus relate to the spin (I) of the same nucleus?

 

μ = ( h I

μ = magnetic moment

( = gyromagnetic or magnetogyric ratio

I = spin quantum number

h = Plank’s constant over two pi

 

Summary:  The larger the value of the magnetogyric ratio, the larger the magnetic moment of the nucleus and the easier it is to see by NMR spectroscopy.

 

Backup!  To study the magnetic properties of nuclei, experimentalists put the nuclei in a strong magnetic field with a value of Bo in units of Tesla.

What’s a Tesla?

1 T = 10,000 gauss = 42.6 MHz

 

What happens when you place a nucleus with spin (I ¹ 0) into an applied magnetic field (strength = Bo)?

 

Precession:  The circular movement of the magnetic moment in the presence of the applied field.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


Situations:

1.)              No Magnetic Field (B0); Nuclei with I = ½


-Observe: equal populations of Iz = +1/2 and Iz = -1/2

 

-SATURATION:  The condition that exists when the upper and lower energy states of nuclei are equal.  (no observed signal by NMR)

 

2.)              Small Magnetic Field (B0); Nuclei with I = ½

 

-Observe:  higher population of Iz = +1/2 than Iz = -1/2

 

-In the presence of B0, the +1/2 spin is of slightly lower energy than the –1/2 spin resulting in a higher population of +1/2 nuclei.

 

3.)              Large Magnetic Field (B0); Nuclei with Iz = ½

 

-The energy difference between the +1/2 and the –1/2 spin states increases resulting in an increased population of the +1/2 state.

4.)              Nuclei of spin = ½ of different gyromagnetic ratio (g) at constant B0

 

-The larger the gyromagnetic ratio (g), the larger the energy difference between Iz = +1/2 and Iz = -1/2.

 

WOAH NELLY!

 

From physics:  DE = h no  where no = linear frequency

 

For NMR, the concern is on the angular frequency of the precessing magnetic moment (m) about B0.

 

Larmor Frequency: The angular frequency (wo) for the precessional motion of the magnetic moment around B0.

 

*The magnetic moment (m) is nuclei specific!

*The gyromagnetic ratio (g) is the proportionality between wo and B0.

*g = a constant for each nucleus that determines the energy dependence of B0.  Thus g and m are both nuclei specific.

wo = 2 p n

n = Angular Frequency

wo = Larmor Frequency in radians per second

 

wo = g B0

 

DE = g B0 h/2 p = wo h/2 p = h no

 

*Apply a second magnetic field, B1 = wo (Larmor Frequency) and the nuclei will flip spin!

 

Absorption of Energy                                                         Emission of Energy

+ ½ ® - ½                                                                       - ½ ® + ½

 

-Excess + ½ when the system is in equilibrium with the magnetic field.

 

-RESONANCE:  The net absorption of energy caused by an electromagnetic wave hitting a nucleus at the Larmor frequency (spin flip).

Because the linear frequency of a nucleus is dependent on the structural environment of the nucleus, NMR is a good structural tool.

 

Commonly observed spin (1/2) nuclei include 1H, 13C, and 15N.  What is the energy difference between their spin states?  How do we know?

 

What is the B0 of a 750 MHz spectrometer in Tesla?  At what frequency would you expect to observe 1H, 13C, and 15N?

At B0 = 6.34 T = _________gauss = __________MHz

 

B0

1H

13C

15N

6.34 T

DE =

DE =67.9 MHz

DE =22.8MHz

750 MHz

DE =

DE =

DE =

 

Backup:  Because the linear frequency of a nucleus is dependent on the structural environment of the nucleus, NMR is a good structural tool.

 

Are all protons in a molecule the same?  If they were, what would you see?

 

The observed resonance frequency (no) depends on the molecular environment as well as on g and B0.

 

What three properties does the electric cloud surrounding the nucleus of an atom possess?

 

SHIELDING: The electronic modulation of the B0 field caused by the electrons surrounding a given nucleus.

 

DIAMAGNETIC SHIELDING:  The magnetic field generated by the valence electrons surrounding a nucleus that opposes the applied magnetic field.  The greater the strength of the electronic environment, the lower the frequency of precession of the nucleus.

 

CHEMICAL SHIFT:  The variation of the resonance frequency with shielding.

 

Shielding is the equivalent of opposing the magnetic field and is characterized by:

= more electrons around a nucleus

= a low frequency precession

= a smaller chemical shift value (ppm), i.e. an upfield shift

 

Deshielding   = decreasing the magnitude of the electron cloud

= neighboring an electron withdrawing group

= high frequency precession

= large chemical shift value (ppm)

= downfield shift

 

The impact of shielding (or deshielding) causes a difference in chemical shift of nuclei that is very small.

 

Thus to observe the chemical shift, a reference compound is used as an internal standard.  TMS is the standard!  The solvent is often used as a standard in research situations.

 

 

 

The chemical shift (d) equals the shift (Hz) divided by the spectrometer frequency (MHz).  Thus 1 over one million = 1 ppm.


The higher the magnetic field, the greater the shift of the nuclei subjected to that magnetic field.

HOW IT ALL HAPPENS:  NMR Instrumentation

 

SAMPLE:

 

Solvent, unknown compound [£1 %], 5 or 10 mm tube, spun » 15 Hz.

 

 

MAGNET:

 

6.34 T = 63,400 gauss = 270 MHz, superconducting cryomagnet in liquid He (T=4K), surrounded by liquid N, shim coils, and probe.

 

PULSE:

 

Powerful short monochromatic radiofrequency burst of energy!

All of the magnetic nuclei in a molecule are excited simultaneously.

The uncertainty principle accounts for a range of frequencies to be covered by the single burst.

 

 

DETECTION:

 

Relaxation:  The return of the excited nuclei to their original state.

 

Free Induction Decay (FID):  Nuclei emit electromagnetic radiation at various frequencies dependent upon their electronic environment.  The greatest emission is immediately following a pulse.

A receiver coil absorbs the emitted energy and records the signal as a time-domain signal or FID.

 

For a 270 MHz NMR spectrometer, we observe the 1H chemical shift in the range of 270,000,000 Hz to 270,002,700 Hz.  We use computers to take the difference and focus on the range of 0-2,700 Hz or 1-10 ppm.

 

The FID is the sum of all decaying sine waves for nuclei of variable chemical environment.  The FID by itself doesn’t tell us what we want to know.

 

The FID is digitized by an ADC (Analog to Digital Converter)!

 

Fourier Transform (FT):  A computer program that analyzes and interprets the frequencies emitted by individual nuclei.

 

The FT interprets the FID for us and gives us a direct indication of the electronic environment for each magnetically active nucleus.

 

Signal/Noise Ratio

 

Noise:  Random electronic signals that are usually visible as fluctuations of the baseline in the signal.

S = signal

N = noise

n = scans

What to think about!


S/N

n

Time

1

1

7.5 sec

10

100

12.5 min

32

1000

2.08 hr

100

10000

20.8 hr

400

40000

3.5 days

 

LOCK:

 

The signal that you optimize and maintain during your NMR experiment is a deuterium (2H) signal.

 

The FID’s can only be added by a FT contingent upon the maintenance of the applied magnetic field (B0).

 

If the field shifts, the FT will be meaningless!

 

The deuterated solvent signal is constantly measured such that the B0 maintains a constant n.

 

For B0 = 6.34 T, n = 41.2 MHz

 

REFERENCE:

 

The sample resonance frequencies are typically compared to their difference in chemical shift from TMS or the NMR solvent.

 

INTEGRATION:

 

Difficult to get accurate values

 

a.)              must be noise-free

b.)              baseline must be flat

c.)              all nuclei must have identical responses

d.)              all nuclei must fully relax between pulses

e.)              obtain the ratio of hydrogens not the number

CHEMICALLY EQUIVALENT

 

All of the protons in a chemically identical environment are said to be chemically equivalent.

Same environment = Same chemical shift!

When all of the protons in a molecule are equivalent, only one NMR absorption peak will be observed.

 

How many peaks do you expect to see for each of the molecules below?

 


LOCAL DIAMAGNETIC SHIELDING

 

This typically refers to electron withdrawing groups that remove the intensity of the electron shield around neighboring protons.

 

*Tables of chemical shifts are useful, but intuition is worth a lot more!

 

Molecule

ppm

Molecule

ppm

TMS

0

Methane

0.2

Hydrocarbon

1-2

Methyl iodide

2.2

H-C-X where X=d- element

3-5

Methyl bromide

2.7

Alkenes

5-7

Methyl chloride

3.0

Aromatics

7-8

Methyl alcohol

3.4

Aldehydes

9-10

Methyl fluoride

4.3

Carboxylic Acids

10-12

chloroform

7.3

 

 

For hydrocarbons:

sp3                                                    sp2                                                      sp

methyl                  0.9 ppm        methylene    1.2 ppm        methine                 1.5 ppm

 

1.)           Spectrum 1

Molecular forumula = C7H15Cl

1.08 ppm = 3 H                         1.59 ppm = 2 H


Spectrum 2

Molecular Formula: C5H9Cl3

1.99 ppm = 6 H                         4.31 ppm = 2 H                           6.55 ppm = 1 H


“Anisotropic” = non-uniform magnetic field

 

Explanation of Chemical Shifts:

 

1.)              Hydrocarbon = 1-2 ppm; shielded environment, upfield shift, degree of shielding decreases with hybridization.

 

2.)              Alkynes = 2-3 ppm; protons are shielded based on alignment with the magnetic field accountable to anisotropy.

 

3.)              Halogenated hydrocarbon = 3-5 ppm; deshielding occurs based on the electron withdrawing nature of the halogen.

 

4.)              Alkene = 5-7 ppm; the p electrons deshield vinylic protons due to anisotropy.

 

5.)              Aromatics = 7-8 ppm; the conjugated p electrons of the aromatic ring deshield protons even more due to anisotropy.

 

6.)              Aldehydes = 9-10 ppm; combination of an alkene and an electronegative atom = lots of deshielding.

 

7.)              Carboxylic Acids = 10-12 ppm; combination of resonance and electronegativity causes lots and lots of deshielding.

 

8.)              Hydrogen Bonding = protons that are able to be involved in hydrogen bonding interactions have a chemical shift that is based on concentration, temperature, and the solvent.

 

Acids                                       RCOOH                                      10.5-12 ppm

Phenols                                    ArOH                               4.0-7.0 ppm

Alcohols                                   ROH                                0.5-5.0 ppm

Amines                                              RNH2                                0.5-5.0 ppm

Amides                                              RCONH2                           5.0-8.0 ppm

Enols                                        CH=CH-OH                       >15 ppm

 

Spin-spin Splitting = n + 1 Rule = The influence of neighboring spins on the multiplicity of peaks.

Coupling Constant:  3JHH

 

A measure of how strongly the nuclear spins influence each other for one nucleus split by a neighboring nucleus three bonds away.

 

The strength of the coupling is measured by the distance between the two peaks for the resonance of one nucleus split by another.

 

Commonly observed splitting patterns!


*Protons that are three bond neighbors can be spin up (+ ½) or down    (- ½).

 

If neighboring protons are both the same spin and spin up, there is a deshielding effect.

 

If neighboring protons are of opposite spin, there is a shielding effect.

 

Based on your knowledge of organic chemistry, what would you expect the spectrum of 1,1-dichloropropane to look like?  Explain the splitting patter observed!

 

Use Pascal’s Triangle to make sense out of the splitting pattern!

 

 

Back to coupling constants:

 

A measure of how strongly a nucleus is affected by the spin states of its neighbor.

 

THE COUPLING CONSTANTS OF THE GROUPS OF PROTONS WHICH SPLIT ONE ANOTHER MUST BE IDENTICAL!

 

The usefulness of coupling constants comes from their ability to distinguish stereochemistry, carbon atom hybridization, and nearest neighbors.