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Spectroscopy

A technique for analyzing the structure of molecules, usuallybased on difference in how they absorb electromagnetic radiation

1. Nuclear magnetic resonance (NMR)2. Infrared (IR)3. Ultraviolet (UV)4. Mass spectrometry (MS)

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History of Nuclear Magnetic Resonance(NMR)

• NMR was developed in the late 1950’s• Today NMR is arguably the single most important techniqueavailable to chemists for determination of molecular structure• Felix Bloch and Edward Purcell were awarded the Nobel Prizein physics in 1952.• Kurt Wütrich was awarded the Nobel Prize in chemistry 2002

What does NMR tell us?

Information about the number and types of atoms in a molecule.Information regarding atom connectivity

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Nuclear Magnetic Resonance (NMR Spectroscopy)

Utilize radio frequency to excite nuclear spin (property ofa particular nucleus)

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Not all elements/isotopes are NMR active.

• Nuclei with even mass number and even atomic number havenuclear spin quantum number (I=0) of zero

• Odd mass number and even/odd atomic number haveI=1/2

• Even mass number but odd atomic number have integer valuesI= 1,2, 3, etc

Only nuclei with non zero nuclear spin give NMR spectra

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1. Nuclear magnetic moment (a consequence of nuclear spin)• a nucleus is a charged particle• spinning of a charged particle results in a magnetic field• the nuclei behave (or at least we conceptualize them) as small bar magnets• As such, these magnets can be affected by other external magnets.

Random Collection of Nuclear Spin StatesNo External Magnetic Field

Apply External Magnetic

Field B0

Direction of B0

Nuclear Bar Magnets

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1H and 13C Nuclei

• I = 1/2• # of spin states = 2• Values = +1/2 and -1/2

•At 7.05 T the difference in energy between spin states for 1H isapproximately 0.0286 cal/mol corresponding to 300 MHz

•At 7.05 T 13C energy difference is onlyt 0.00715 cal/mol, corresponding to75 MHz

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B0 = external magnetic field

“Resonance”

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• The precession frequency of the nucleus in an applied fieldmust match, or be in resonance with, the appliedelectromagnetic pulse as to “flip” the spins of desired nuclei.

• The absorption frequency υ is proportional to B0 . The resonancefrequency for Hydrogen nuclei is 90 MHz at H0 = 21, 150 gauss (G), 180MHz at H0 = 42300 gauss (G).

• Energies in this range 300-700 MHz correspond to radiofrequency.

Fig 11.4

Field Strength

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How does this all translate intoOrganic Chemistry?

Let consider the following molecule

Cl

H

O

H

H

HH

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• Nuclei (1H or 13C) are raised to the higher energy level, in whichtheir magnetic moments are opposed to the external field

• The exact amount of energy required for the transition dependson the strength of the magnetic field experienced by the nuclei (gives a spectrum) • Each nuclei requires a different amount of energy to promote its transition from the lower state to the higher state

After pulsing the nuclei with the appropriate RF….

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Chemical Shift

Resonance

Why are there peaks are different locations?

Sample NMR spectrum…Methylacetoacetate

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Another 1H NMR Spectrum

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• Not all the nuclei in a molecule experience the same externalmagnetic field (B0).

• The electrons around a nucleus shield it from the effects ofthe external field

• Therefore, atoms in different electronic environments in amolecule experience the external field to different degrees

Shielded (upfield) nuclei require greater energy to promote spin flipthan deshielded (downfield) nuclei.

Origin of Chemical Shift

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Lower Energy Transition Higher Energy Transition

Downfield Upfield

ShieldedDeshielded

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CH3F CH3Cl CH3Br

fluoromethane chloromethane bromomethane

Electronegativity

Ring current

Predicting 1H Resonance for the following compounds

Factors influencing shielding

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• Not all the nuclei in a molecule of an organic compoundexperience the same external magnetic field

• electrons around a nucleus shield it from the effects of theexternal magnetic field

Take Home Message:

• Adding electron density increases shielding; removal ofelectron density causes deshielding

www.o-m-p.co.uk/gladiator.htmref

Shielding

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• Even in complex molecules, different carbon atoms are likelyto have different chemical shift

•Range of possible chemical shifts ~250 ppm

• Peak areas do not correspond to the number of carbons

• Carbon spectra (in this class) are typically decoupled from the proton nuclei attached to them.

13C vs. 12C The natural abundance of 13C is approximately 1% The natural abundance of 12C is approximately 99%

13C NMR Spectroscopy

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What good is 13C NMR?

Cl

KOH

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Proton Equivalency

NMR is used to find out how many kinds of electronicallynonequivalent hydrogens are present

A. Chemically nonequivalent: Replace H with D will result in

H

C

C

C

C

H

H H

H H

H H

H H

constitutional isomers

Different NMR resonance

Replace H with D

Replace H with D

D

C

C

C

C

H

H H

H H

H H

H H

H

C

C

C

C

H

H H

H H

H H

D H

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Proton Equivalency

B. Homotopic Prortons: Replace H with D will result in

H

C

C

C

C

H

H H

H H

H H

H H

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identical structure

Same NMR resonance

Replace H1 with D

Replace H4 with D

H

C

C

C

C

H

H H

H H

D H

H H

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H

C

C

C

C

D

H H

H H

H H

H H

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Proton Equivalency

C. Enantiotopic Protons: Replace H with D will result in Enantiomers

Same NMR resonance

Replace H with D

H3C

C

C

CH3

H

H

H

H

12

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4

Replace H with D

H3C

C

C

CH3

H

D

H

H

12

3

4

H3C

C

C

CH3

H

H

H

D

12

3

4

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Proton Equivalency

D. Diastereotopic Protons: Replace H with D will resultin

Diastereomers

Different NMR Resonance

H3C

C

C

CH3

H

H

H

OH

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4

Replace H with D

Replace H with DH3C

C

C

CH3

D

H

H

OH

12

3

4

H3C

C

C

CH3

H

H

D

OH

12

3

4

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What we learned about 1H NMR so far

Relative location of δ• The chemical shift of each signal gives us information related tothe type of hydrogen (or its magnetic environment)

Chemical Equivalency •The # of signals describes the number of equivalent sets of hydrogens in the molecule

Integration•gives us the relative number (ratio) of hydrogens for each signal

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1H NMR: Spin-Spin Splitting

13C spectra are typically decoupled. That is, the spins from the1H nuclei covalently bonded to the 13C nuclei are decoupledfrom each other.

n = equivalent neighboring protons

Spin-spin splitting, the phenomenon of multiple absorptions iscaused by the interaction , or coupling, of the spins of nearby nuclei.

Informations offers by coupling connectivity

(n+1) rule Prediction coupling patterns

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n + 1 Rule

n = equivalent neighboring protonsPrediction coupling patterns

1. Chemically equivalent protons do not show coupling2. The signal of a proton that has n equivalent neighboring

protons is split into a multiplet of n + 1 peaks with couplingconstant, J (distance between the peaks within a multiplet, Hz)

3. Two groups of protons coupled to each other have the samecoupling constant J.

Ex) CH3CHCl2

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1HNMR of CH3CHCl2

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C C

H H

Cl

Cl Cl

HC2H3Cl3

triplet doublet

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Calculating J

δ 5.81, 5.78, 5.75

Instrument: 300 MHz

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Spin-Spin Coupling with Multiple BondsAssigning δ and making sense of coupling pattern

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Complex Splitting Patterns in aromatic hydrogens

CH3

Aromatic hydrogensBenzylic hydrogens

C7H3

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Aromatic Hydrogens

C

OH

C7H6O

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Complex Splitting Patterns

Making sense of 1H NMR spectrum of 2-bromo-4-nitrotoluene.

4-bond couplings: one of the bonds has to be a double bond.

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Highly Complex Splitting: Not exactly what I expected!

Br C

H

C

H

H

H

C

H

H

C C

H

H

H

H

H

1 2 3 4 5

• As one moves further awayfrom the electronegative atom(Br, from Carbon 1-5), the chemical shifts of inequivalent 1H nuclei become very similar.

• The appearance of resonances(splitting patterns) are typicallydistorted when their chemicalshift values are close to nuclei they are coupled to.

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The Effect of Chemical Exchange on Spin-Spin Coupling

• Hydrogens that can participate in hydrogen bonding are susceptibleto chemical exchange

R O

H

N RH

H C

O

OHR

• Chemical exchange results in the following spectral characteristics:1. Broadening2. Loss of coupling3. Variable chemical shift

• Resonance of exachangeable protons depends on:1. Concentration2. Extent of H-bonding3. Extent of exchange

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Magnitude of Spin-Spin Coupling (J values)