NUCLEAR MAGNETIC RESONANCE spectroscopy NMR spectroscopy Alkhair Adam

NUCLEAR MAGNETIC RESONANCE spectroscopy NMR spectroscopy Alkhair Adam Khalil, B. Pharm. , M. Pharm. Department of Pharmaceutical Chemistry College of Pharmacy – Karary University

References: 1. 2. 3. 4. 5. 6. Analytical Chemistry by Gary D. Christian Fundamentals of Analytical Chemistry by Douglas A. Skoog Pharmaceutical analysis by David G. Watson Introduction to spectroscopy by Donald L. Pavia et. al. Pharmaceutical analysis of drugs by Ashutosh Kar Modern Analytical Chemistry by David Harvey

H NMR: Intensity of Signals 1 • The relative intensity of H NMR signals also provides information about a compound’s structure. 1 • For example, in the H NMR spectrum of CH 3 OC(CH 3)3, the ratio of the area under the downfield peak (due to the CH 3 O – group) to the upfield peak [due to the – C(CH 3)3 group] is 1: 3. 1

• Integrals can be manually measured, but modern NMR spectrometers automatically calculate and plot the value of each integral in arbitrary units. • This tells the ratio, not the absolute number of protons. • Integration ratios are approximate, and often values must be rounded to the nearest whole number. • Knowing the molecular formula of a compound and integration values from its H NMR spectrum gives the actual number of protons responsible for a particular signal. 1

• Step [1]: Determine the number of integration units per proton by dividing the total number of integration units by the total number of protons. • Total number of integration units: 54 + 23 + 33 = 110 units • Total number of protons = 10 • Divide: 110 units/10 protons = 11 units per proton

• Step [2]: Determine the number of protons giving rise to each signal. • To determine the number of H atoms giving rise to each signal, divide each integration value by the answer of Step [1] and round to the nearest whole number.

Problems:

H NMR: Spin–Spin Splitting 1 • The H NMR spectra you have seen up to this point have been limited to one or more single absorptions called singlets. • In the H NMR spectrum of Br. CH 2 CHBr 2, however, the two signals for the two different kinds of protons are each split into more than one peak. • This can be used to determine how many protons reside on the carbon atoms near the absorbing proton. 1 1

• Spin–spin splitting occurs only between nonequivalent protons on the same carbon or adjacent carbons. • Spin–spin splitting arises because protons are little magnets that can be aligned with or against an applied magnetic field, and this affects the magnetic field that a nearby proton feels.

Pascal’s Triangle:

• When two protons split each other’s NMR signals, they are said to be coupled. • The spacing between peaks in a split NMR signal, measured by the J value, is equal for coupled protons.

The Rules of Splitting • Rule [1] Equivalent protons don’t split each other’s signals. • Rule [2] A set of “n” nonequivalent protons splits the signal of a nearby proton into “n + 1” peaks. • Rule [3] Splitting is observed for nonequivalent protons on the same carbon or adjacent carbons.

• Note that: The splitting of an NMR signal reveals the number of nearby nonequivalent protons. It tells nothing about the absorbing proton itself.

• Predicting splitting is always a two-step process: • Determine if two protons are equivalent or different. Only nonequivalent protons split each other. • Determine if two nonequivalent protons are close enough to split each other’s signals. Splitting is observed only for nonequivalent protons on the same carbon or adjacent carbons.

Examples: Examples

Problems:

More Complex Examples of Splitting

Spin–Spin Splitting in Alkenes

OH Protons • Under usual conditions, an OH proton does not split the NMR signal of adjacent protons. • The signal due to an OH proton is not split by adjacent protons.

Protons on Benzene Rings

Protons on Benzene Rings

Protons on Benzene Rings

Protons on Benzene Rings

1 • Using H NMR to Identify an Unknown • To be continued next lecture…. .

Questions !