• Intro to Spectroscopy

• NMR Spectroscopy:– How it works– Chemical Shift in 1H NMR– Equivalent & Non-equivalent Hydrogens

Lecture 2

Organic Chemistry: From Yesterday to Today

Late 1700’s: Atomic Theory

1800’s: Organic Structural Theory- Combustion Analysis- Functional Group Tests

1900’s: Synthesis and Analysis

Today: Automated Synthesis &Spectroscopic Analysis

Spectral Analysis

Each type of spectral analysis has its value in determining/confirming the structure of a compound. Spectroscopy allows us to “see” the molecule.

NMR (Nuclear Magnetic Resonance) Spectroscopy:• Different types of nuclei in a molecule (1H & 13C)• 1H NMR: Aids in the determination of bond connectivity within a molecule &

the pieces of a molecule

IR (Infrared) Spectroscopy:• Confirms the presence of functional groups within a molecule

MS (Mass Spectrometry):• Determines the mass of a compound• Also aids in the determination of pieces of the molecule

Types of Analysis

NMR (Nuclear Magnetic Resonance Spectroscopy):• Uses radio waves (electromagnetic radiation)• Interacts with sample’s nuclei in the presence of a magnet• Effect: nuclei flip and relax (known as resonance)

IR (Infrared Spectroscopy)• IR radiation• Interacts with molecule as a whole• Effect: bond vibrations within molecule

MS (Mass Spectrometry)• No radiation used• Interacts with and destroys molecule; fragments molecule• Effect: creates ions and neutral fragments of molecule

1H NMR Spectrum of Ethanol

ppm

CH3CH2OH

IR Spectrum of Hexanol

Wavenumber (cm-1)

% T

ransm

itta

nce

Mass Spectrum of Phenetole

OCH2CH3

MW = 122

m/z (mass to charge ratio)

Inte

nsi

ty

122

94

77

Nuclear Magnetic Resonance

Use: To assist in the elucidation of a molecule’s structure

Information Gained:• Different chemical environments of nuclei being analyzed (1H nuclei):

chemical shift• The number of nuclei with different chemical environments: number

of signals in spectrum• Determine the number of protons that are adjacent to one another:

splitting patterns• The numbers of protons with the same chemical environment:

integration• Determine how many protons are bonded to the same carbon:

integration• Determine which protons are adjacent to one another: coupling

constants

How does NMR work?

Basic Idea:

In the presence of an applied magnetic field (Bo) - the NMR instrument:

1. Irridate the sample with radiofrequency radiation

2. Nuclei resonance: excite magnetic transitions

3. Measure the energy absorbed/released by nuclei

4. Obtain a spectrum

How does NMR work?

Facts that allow NMR to work:

1. Nuclei have a spin (like electrons).2. Nuclei that have odd mass or odd atomic number have a quantized spin

angular momentum and a magnetic moment.3. The allowed spin states a nucleus can adopt is quantized and is

determinedby its nuclear spin quantum number, I.

1H and 13C nuclei have I = 1/2. Thus, there are two allowed spin states: +1/2 and -1/2.

1H NMR Spectroscopy

• 1H nuclei have magnetic spin, I = 1/2.

• The nuclei can either align with (+1/2) or oppose (-1/2) the applied magnetic field, Bo (from the NMR instrument).

• When the nuclei absorb the radiofrequency pulse (a specific energy is absorbed since the spin states are quantized!), the spin flips - resonance.

• When the pulse is over, the spin relaxes back to its original state.

The spin releases the energy that it had originally absorbed - this is the energy that is measured.

This happens to each 1H nuclei in the sample, but not every 1H nuclei are the same.

How does NMR work?

Getting a Spectrum

• Pulse sample with radiofrequency radiation, spin flip - resonance.• After pulse, the excited nuclei lose their excitation energy and return to their original state - relax.

• As the nuclei relax, they emit electromagnetic radiation; results in free-induction decay (FID)• FID contains all emitted frequencies:

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

• Fourier transform (FT) is performed on the FID.• FT extracts the individual frequencies on the different nuclei; results in a spectrum.

How does NMR work?

Nuclei are charged and if they have spin, they are magnetic

Applied Magnetic Field = Bo

Energy of transition = energy of radiowaves

Higher energy state: magnetic field opposes applied field

Lower energy state: magnetic field aligned with applied field

An NMR Diagram: On the Inside

+ -

N S

RFtransmitter

RFReceiver

Note modern NMRs use superconducting magnets to attain very strong magnetic fields

Chemical Shifts

Not all proton nuclei resonate at the same frequency.

Proton nuclei are surrounded by electrons in slightly different chemical environments - nuclei are shielded by valance electrons that surround them.

As a result, the nuclei are shielded from Bo to an extent that depends on the electron density around it.

A shielded nucleus will feel a diminished Bo and will absorb radiofrequency radiation at a lower frequency - have a lower ppm value.

A deshielded nucleus will feel a stronger Bo and will absorb radiofrequency radiation at a higher frequency - have a higher ppm value.

Different nuclei will be shielded differently and, as a result, will have differentresonance frequency - different ppm values - different chemical shifts.

Chemical Shifts

•Protons near an electronegative group will be deshielded - feel a stronger Bo - have a higher ppm value.

•Electronegative groups: OH, OR, Cl, F, Br, N•Other deshielding groups: C=C, phenyl, C=O

5.0 0.01.02.03.04.06.07.08.09.010.011.012.0

Chemical Shift, (ppm)

CO2H

CHO

ArH C=CH

X-CH

O-CH

C CH

O-H

N-H

COCH

CH, CH2

CH3

Shielding/Deshielding Effect

1H NMR Spectrum of Ethanol

ppm

CH3CH2OHTMS

Three signals - three different types of H’s

a ab

b

c

c

downfield upfield

Chemical Shifts

TMS - Tetramethylsilane (Me4Si) is the internal reference used.TMS’s chemical shift is set at zero since most peaks appear more downfieldfrom it.

The Delta () Scale• An arbitrary scale• 1 = 1 part per million (ppm) of the spectrometer operating frequency. For example, if using an 80 MHz instrument to run a 1H NMR spectrum, 1 would be 1 ppm of 80,000,000 Hz, or 80 MHz.• Since the radiofrequency absorption of a nuclei depends on the magnetic field strength, chemical shift in Hz would vary from instrument to instrument.• Thus, report the nuclei absorption in relative terms () as opposed to absolute terms (Hz). This way, the chemical shifts will be the same for nuclei of a sample despite what instrument you use - leads to correlation charts!

Equivalent & Non-Equivalent Hydrogens

As seen in the 1H NMR spectrum of ethanol, the number of signals equals the number of different types of protons in a compound.

General rules: • Protons attached to the same sp3 carbon are equivalent/homotopic (if there are no chiral centers in the molecule; if there are, could be equivalent or non-equivalent).• If there is symmetry in the molecule, protons that are symmetrical will have the same signal, the same chemical shift and be equivalent.

Considerations:• Protons attached to the same sp2 carbon (in alkenes) need to be evaluated for equivalency.• Methylene protons (on a CH2 group) are diastereotopic if a chiral center existsthe molecule and are therefore non-equivalent.

Perform a substitution test to check for equivalency

Equivalent & Non-Equivalent Hydrogens

Consider the following molecules. Determine which protons are equivalent and non-equivalent. Predict the number of signals that would appear in the 1H NMR spectra of these compounds.

H

OH

Cl

O

NH2

NH2

NH2

CH3

Equivalent & Non-Equivalent Hydrogens

Considerations:• Protons attached to the same sp2 carbon (in alkenes) need to be evaluated for equivalency.

• Methylene protons (on a CH2 group) are diastereotopic if a chiral center exists the molecule and are therefore non-equivalent.

Perform a substitution test to check for equivalency

Equivalent & Non-Equivalent Hydrogens

Substitution Test:1. Change questionable H’s to a differentgroup like D.2. Create two new molecules.3. Compare these two newmolecules.

H3C

CH3

H

H

H

H3C

CH3

H

D

H

H3C

CH3

D

H

H

O

H3C

Cl

HH

O

H3C

Cl

HD O

H3C

Cl

DH

Example 1

Example 2