Applications of NMR Flashcards
Where would a solvent peak of CDCl3 show up in 1H NMR and what causes it
δH = 7.27
Due to residual amounts of CHCl3
How is the δH value calculated?
Taking the average of the peaks to two decimal places
How is the J value calculated?
Taking the difference between the peaks and multiplying by the frequency of the spectrometer
Generally is coupling seen in a C13 spectum?
Generally the spectra are proton decoupled but could show coupling for other NMR active nuclei
What are the typical chemical shifts for carbon NMR?
δC 220-150 C=O e.g ketones, aldehydes (δC 210-190 esters and amides)
δC 150-100 - C=C and aromatic
δC 100-50 - R3COH, R2CHOH, RCH2OH
δC 60-40 - R3CN, R2CHN, RCH2N
δC 50-0 - other C, CH, CH2 and CH3S
How would CDCL3 show up in a 13C NMR and why?
Show up as a 1:1:1 triplet
Due to coupling from deuterium - Deuterium has spin of 1 and so three lines show up due to (2I+1) rule
Describe the chemical shift scale
For 1H NMR the scale generally goes from 0-10 ppm
High ppm value is downfield and deshielded
What does integration tell us
Tells us how many protons the signal is worth
What does multiplicity tell you and what doe sit come from?
Due to coupling
Tells you about the environment
3 bond coupling is the most common type of coupling although 2 and 4 bond coupling is possible
Coupling is a through bond effect - equivalent protons do not couple and protons coupledto each other have the same J values
What is distortionless Enhancement by Polarisation Transfer (D.E.P.T)
Heteronuclear pulse sequence which involves the simultaneous application of a programmed sequance of pulses to the 1H and 13C nuclei
D.E.P.T provides an enhancement of intensity by changing the pulse angle so it is possible to change the phase of a signal.
When θ = 135°:
CH and CH3 point up
CH2 point down
C (quaternary) do not appear
What happens to a proton when it couples to two other that do not have the same J value?
First J coupling constant splits δH peak into 2 then the second J coupling constant splits each of these loines into two again
In the spectrum you would see 4 peaks of equal intensity (not a quartet which shows 1:3:3:1)
Peaks 1-2 gives smaller J value
Peaks 1-3 gives largerJ value
Peak 1-4 give sum of J values
This is called a doublet doublet
What happens to a proton if it is coupled to two protons in different environments with the same J value by chance?
The signal shows up as an apparent triplet (has a 1:2:1 ratio) but is different to a proton coupled top 2 protons in the same environment
Should be reported as a doible doublet with two dentical J values
The same effect is seen when a proton couples to 3 protons in different environments with the same J values by chance - shows 1:3:3:1 as an apparent quartet but is reported as a double double doublet
What splitting pattern is shown for a proton coupled to 3 others in different environments with J values 12, 4 and 2Hz
Appearance: 8 lines - double double doublet
reported as ddd J = 12,4,2 Hz
Lines 1-2 shows 2Hz
Lines 1-3 shows 4 Hz
Lines 1-5 shows 12 Hz
What is the splitting pattern for a proton that couples to 3 others with J values 12Hz, 10Hz and 4Hz
Appearance: 8 lines
Shows crossover between the lines: when the sum of the second two J values is greater than the first cross over occurs
Lines 1-2 gives 4 Hz
Lines 1-3 gives 10 Hz
Lines 1-4 gives 12 Hz
What is the splitting pattern for a proton couled to 3 others in different environments with J vaues 12, 10 and 2 Hz
Appearance 7 lines: middle lines coincident
LInes 1-2 show 2 Hz
Line 1-3 show 10 Hz
Lines 1-4/5 show 12 Hz
What is the splitting pattern for a proton coupled to 3 other in different environments with J values 12, 5 and 5 Hz
Appearance 6 lines - looks like a doublet of triplets
Lines 1-2 shows 5Hz
Lines 1-4 shows 12 Hz
What is the splitting patter of a proton coupled to 3 others in different environments with J values 12, 12 and 5 Hz?
Appearance 6 lines - looks like triplet of doublets
Lines 1-2 gives 5 Hz
Lines 1-3 gives 12 Hz
What is roofing?
The intensity of doublet peaks is not always equal so we sometimes see a roofing effect where one of the peaks is smaller than another - usually see between two separate doublets
If separation between peaks of different environemnts is good the roofing effect is reduced
If separation is poor the two doublets can look like a quartet
What is 2J coupling?
Coupling through only 2 bonds when the protons are different
The magnitude of the J constant is often large
Average J value- 12 Hz
What are the factros affecting 2J coupling?
Adjacent electronegative atoms reduce 2J value ~ 10.5 Hz
Adjacent pi systems increase 2J value ~ 16 Hz
terminal alkenes have small 2J values ~ 0-3 Hz
Where can 2J coupling be observed?
When 2 protons are bonded to the same carbon atom but are in different environments
These can be found on terminal alkenes (when an alkene has 2 hydrogens on one end) or when a molecule has 1 or more chiral centres
What is the typical range of J values for 3 bond coupling and the average value?
Range of values: 0-12 Hz
Average value: 7Hz
How do J vlaues depend on dihedral angle?
Karplus equation: 3J = 4.22 - 0.5cosΘ + 4.5cos2Θ
When Θ = 0° 3J = 9-12 Hz
When Θ = 90° 3J = 0 Hz
When Θ = 180° 3J = 9-12 Hz
What can J values tell you about cyclic systems?
In cyclo ring the conformation is often fixed (dihedral angle fixed)
The magnitude of 3J can tell you about the orientation of the protons
There are two types of protons: axial and equatorial
What is the 3J value for axial axial coupling?
Θ = 180°
3J ax-ax = 9-12 Hz
What is the 3J value for axial equatorial coupling?
Θ = 60°
3J = 2-6 Hz
What is the 3J value for equatorial equatorial coupling?
Θ = 60°
3J = 2-6 Hz
What 2J coupling will you see in cyclo compounds?
2J coupling can be seen between axial and equatorial protons on the same carbon
Typical value 2J = 12Hz
2J does not depend on the dihedral angle
What are the typical values for the 3J coupling constants for trans, cic and cyclic alknes?
Trans: 3J = 14-16 Hz
Cis: 3J = 8-10 Hz
cyclohexene 3J = 10 Hz
cyclopentene 3J = 6 Hz
cyclobutene 3J = 3 Hz
cyclopropene 3J = 1 Hz
What is 4 bond coupling and what are the typical values?
4J coupling is coupling across 4 bonds (long range)
Requires a pi system or a W shape
Aromatic W coupling: 4J = 0-3 Hz
Allylic coupling: 4J = 0-3 Hz
Cyclohexene W coupling: 4J = 0-3 Hz
What are diastereoisomers?
A stereoisomerthat is not an enantimor
Diastereoisomers have >1 chiral centre
What are diastereotopic protons?
Protons that are chemically different - can be distnguished even by systems that cannot tell right from left - appear at different chemical shifts in NMR
How do OH or NH protons show up?
OH signals can be unpredictable
Chemical shift values vary
signals are often broad but can be sharp and sometimes show coupling.
Both chemical shift valiues and coupling depend on hydrogen binding which depends on solvent, concentration and temperature
R-O-H + H+ <–> R-O-H + H+ - proton exchange faster than NMR timecale - shows broad peak
How can Oh or Nh peaks be discovered?
With a D2O shake:
1) record 1H NMR spectrum as normal
2) Add two drops of deuterium, shake then record 1H NMR spectrum again:
D2O(excess) + R-OH <—> R-OD + H-O-D
Missing signals can be assigned to OH or NH
The H in H-O-D shows up at 4.8
What methods can be used to increase chance of observing coupling to/from OH
Rigorously dry NMR solvent - no H2O (no H+)
Low concentration of compound - exchange is an intermolecular process - lower concentration reduces rate of exchange
Use H bonding solvent (DMSO) - H bonding of OH to DMSO slows rate of exchange
Best situation - dry d6-DMSO
What is the Nuclear Overhauser Effect?
results inchange of intensity of NMR signals of a nucleus when the resonance of some other nucleus in the molecule is saturates - undergopes irradiation by string radiofrequency.
Arise via dipole dipole interactions between saturated and observed nuclei
It is a through space interaction
Gives 3D solution structure of conformation of a molecule - shows protons close in space
How do we measure NOEs?
Measure normal 1H spectrum and observe peaks
Record spectrum while saturating one group
Take the difference between the two spectra - peaks that show up are close in space to saturated environment.
What can we us NOEs to assign?
Trisubstituted alkenes - cannot use J bvalues as they dont exist - look at which groups are close together
Assign stereochemistry in cyclic ring - groups close in space, on same side of the ring will show NOEs
Often used to assign spectra of proteins
What is (2D 1H 1H COSY) spectroscopy?
Uses a pulse sequence which modulates the resonance of each proton in an NMR with the chemical shift of protons which are coupled to it
Presence or absence of spin spin coupling between each proton is obtained.
Output: 2D contour map:
each axis is the 1D 1H NMR spectrum, contours represent signal intensity, diagonal is birds eye view
In COSY what do cross peaks show?
Cross peaks represent coupled protons
if there are no cross peaks those protons are not coupled#a cross peak indicates coupling
What is COSY: 2D 1H 13C HMQC or HSQC?
HMQC = heteronuclear multiple quantum correlation spectroscopy
HSQC = heteronuclear single quantum correlation spectroscopy
identifies 1 bond C-H connectivity
one axis = 1D 1H spectrum
one axis = 1D 13C spectrum
What do cross peaks show in HMQC and HSQC?
Cross peaks show which carbon a particular proton is connected to
a diastereotopic CH2 will show cross peak to from one carbon to 2 protons
a cross peak indicates a C-H bond
What is NOESY 2D 1H 1H
The presence or absence of NOE interactions between each proton is obtained
Each axis is the 1D 1H NMR
Contours represent intensity
Diagonal is a birds eye view
What do cropss peaks show in NOSEY?
Cross peaks represent protons that show NOE (are close in space)
If there are no cross peaks then those protons are not coupled (not close)
Cross peaks indicates two protons close in space
