Applications of NMR Spectroscopy in Organic Chem

Question 1

Give the expected values of 2J splitting.

Answer 1

10-18 Hz for most fixed position hydrogens 0-3 Hz for alkene hydrogens on one side

Question 2

Give the 3J coupling values typical for alkenes and 6-membered rings

Answer 2

14-16 Hz trans alkene 8-10 Hz cis alkene 9-12 Hz trans diaxial 2-6 Hz ax-eq and eq-eq

Question 3

What are typical values of 4J coupling and when does it occur?

Answer 3

0-3 Hz when a W shape is formed, such as in the chair conformation, benzene and in alkenes

Question 4

How does the nuclei environment affect its position in the spectrum? How do different groups affect each other?

Answer 4

A higher number is a more deshielded nuclei, the effect is additive. Conjugation can increase or decrease the shift depending on where the conjugation goes to.

Question 5

How do you determine how many lines a nuclei splits a signal into?

Answer 5

1 + 2I for each nuclei

Question 6

How can DEPT experiments be used to distinguish carbon groups?

Answer 6

The pulse angle can change intensity and phase of certain signals. For θ = 45, all protonated carbons have positive signals, quaternary signals do not appear θ = 90, only CH signals appear and is positive θ = 135, CH3 point up, CH2 point down and CH point up

Question 7

How can identifying one signal in a proton spectra lead to other identifications?

Answer 7

You can match the J values of the splitting between protons that split each other.

Question 8

For a signal split by 2 protons with different J values (dd), how do you measure each J value?

Answer 8

Lines 1 to 2 gives one J value, lines 1 to 3 gives the other J value.

Question 9

What happens when a pair of non-equivalent protons with the same J value (7) split a signal?

Answer 9

An apparent triplet is formed, labelled as dd J = 7, 7 Hz

Question 10

How do you check if your measured splitting values are correct?

Answer 10

Add up all the values, it should be the same as the distance between the 2 furthest apart peaks.

Question 11

If a peak is double as intense, what may have happened?

Answer 11

The splitting pattern has coincided to form the doubly intense peak. This may be due to 2 protons in the same environment, 2 of the same coupling constants by chance or where different coupling constants add up to another (couplings =5, 7, 2).

Question 12

When and why does roofing occur?

Answer 12

When 2 signals that split each other have a very similar chemical shift, they will angle towards each other (in a doublet, the side close to the other signal will increase in height while the other decreases). In general, roofing occurs if |Ha - Hb| < 10 x J value

Question 13

Give typical 2J spitting values, the limits of the range and when this would occur, and the situations where the splitting won’t be in the range

Answer 13

Typical range is 10-18 Hz When a carbon is adjacent to an electronegative atom the splitting will be reduced to ~10.5 Hz Adjacent pi systems (such as benzene and carbonyls) increase the splitting up to 18 Hz In terminal alkenes the coupling is either not seen, or in the range of 0-3 Hz

Question 14

Give examples when geminal CH2 couplings are observed

Answer 14

In ring compounds, in molecules with one or more chiral centre and in terminal alkenes. Generally where there is 2 different environments between the protons.

Question 15

What determines the magnitude of 3J coupling? Give the range of typical values.

Answer 15

A typical range is 0-12 Hz, it depends on the angle between the C-H bonds.

Question 16

Give the common splitting values in cyclohexane rings with a brief description of why each has its magnitude.

Answer 16

3J ax-ax is approximately 9-12 Hz since the CH bonds are 180° to one another 3J ax-eq and eq-eq are approximately 2-6 Hz since the CH bonds are 60° to one another 2J coupling will be approximately 12 Hz

Question 17

What are the typical values for alkene 3J splitting? Explain the origin of each value.

Answer 17

Trans hydrogens are held at 180° to each other and have good orbital overlap so they have a typical range of 14-16 Hz Cis hydrogens are held at 0° so have a typical range of 8-10 Hz

Question 18

What is the trend of 3J values for decreasing cycloalkene ring size?

Answer 18

3J values decreases from 10 Hz for cyclohexene to 1 Hz for cyclopropene.

Question 19

When do 4J couplings occur? What is a typical range and how should they be treated?

Answer 19

4J couplings occur between protons that have a W shape and a pi system have the best overlap. Example systems are benzene, alkene systems and cyclohexane. All have a range of 0-3 Hz. Never look for 4J coupling, just remember it when assigning coupling in the range of 0-3 Hz.

Question 20

Give the general approach for assigning an NMR spectrum.

Answer 20

1. Look at the chemical shift values, assign obvious signals 2. Look at integration values, label signals for clues in conjunction with other data 3. Look at multiplicity, start with protons with few splittings, then match couplings

Question 21

When are protons diastereotopic?

Answer 21

If structures are diastereoisomers, then protons are diastereotopic. This means if there is one chiral centre, the protons on a CH2 group being different produce 2 diastereoisomers, hence they have different chemical shifts. Often the CH2 protons cannot be distinguished and are assigned as a pair of 2 signals.

Question 22

How are OH and NH signals treated in NMR? Why is this the case?

Answer 22

They have a large possible range of chemical shift values and sometimes show coupling to other protons, this depends on the hydrogen bonding which is highly dependant on the environments. A D2O shake is used and the spectrum re-recorded to remove the OH and NH signals since they rapidly exchange with the deuterium faster than the timescale of the experiment. These peaks will be labelled as such in data.

Question 23

How can OH signals be specifically observed and coupled to other signals?

Answer 23

By slowing down the exchange of protons. This can be achieved 3 ways: 1. Using an extremely dry solvent, removing water with a molecular sieve 2. Using a lower concentration of sample, the exchange is an intermolecular process, hence the rate will be lowered 3. Using a hydrogen bonding solvent such as DMSO which will slow down the rate of exchange

Question 24

What is the nuclear overhauser effect and how is it used?

Answer 24

NOE is the change in intensity of the NMR signal due to dipole-dipole interactions between saturated and non-saturated nuclei. They occur through space and are not a coupling. They tell you when nuclei are close in space to one another which allows for further identification of nuclei.

The NOE spectrum is a difference spectrum observed when a certain group of the molecule is saturated with RF pulses (will not show as no relaxtion) which increases the intensity of adjacent groups (dipole-dipole interactions).

Question 25

How should you assign the stereochemistry of trisubstituted alkenes?

Answer 25

Use NOE, coupling can’t be used as there is no copling across the alkene bond.

Question 26

What is a COSY experiment? Sketch the spectra for ethane.

Answer 26

COSY means correlation spectroscopy and it is a square with two 1D spectra as the x and y axis. Each peak is shown on the diagonal and cross peaks are shown for coupled protons.

Question 27

What is the process of using COSY data?

Answer 27

First assign the 1D spectrum and mark them on both axis. Then trace the signals one by one, vertically down. Every point, aside from the one on the diagonal, identifys coupling to the peak thatis shown at the other axis. From this coupling can be confirmed.

Question 28

What alternative COSY experiments can be done?

Answer 28

Proton and ¹³C spectra can be placed on each axis to identify the 1 bond C-H connections in a molecule where a dot shows a connection. With diastereotropic protons, multiple protons will be shown to be connected to a single carbon.

Question 29

What is a NOESY experiment?

Answer 29

A NOESY experiment is a normal two proton COSY experiment with the NOE data overlaid on the graph as well as ‘contours’. This can clearly show the coupling and NOE data together.