 
Hello everyone, welcome to module 13 of the
course on Application of Spectroscopic Methods
and Molecular Structure Determination. In
this module, we will see some aspects of the
variable temperature NMR technique, and how
to study dynamic processes in molecule by
NMR spectroscopy at various temperatures.
Now, NMR spectroscopy is a very powerful tool,
and it can be used for a study of several
different types of dynamic properties of the
molecules. Some of the dynamic processes are
listed here, which can be studied by NMR spectroscopy.
Now conformational change a chair form of
cyclohexane going to another chair form, for
example can be studied by NMR spectroscopy.
Bond rotations carbon-carbon bond or carbon-heteroatom
bond rotating the restricted rotation of this
kind of bonds can be studied by NMR spectroscopy.
When molecules trend to aggregate in solution
such an aggregation phenomenon can be studied
by NMR spectroscopy. A typical would be pi
stacking aggregation of aromatic systems in
solutions. Finally, the fluxional properties
of molecules can also be studied, a very classical
example would be the fluxional property of
bullvalene that has been studied by NMR spectroscopy.
Now, the sample tube in the NMR spectrometer
can be either cooled up to minus 150 degree
Celsius or it can be heated to plus 150 degree
Celsius. This 300 degrees window is accessible
provided the solubility and the solvent melting
point boiling point permit such an operation.
Now if the temperature of the sample can be
cooled to such a wide range of temperatures
then it is possible to study processes that
has activation barrier typically in the range
of about 8 to 25 kilocalories per mole can
be studied using NMR spectroscopy.
Now, let us look at the basic principle behind
the study of variable temperature NMR spectroscopy
for the dynamic processes of molecules. Now
assume a proton can exist into 2 possible
chemical environment. The example that I would
like to site here is the proton in cyclohexane
which can exist either in the equatorial position
or in the axial position. The equatorial position
and the axial positions are distinctly different
chemical environment as we have seen earlier.
So, if NMR can for example, distinguish whether
a proton exist in the axial position or in
the equatorial position that will be a very
valuable information in terms of studying
stereochemistry of cyclohexane kind of molecules.
The ability of NMR to very clearly define
the chemical shift environment of a proton
and hence the chemical shift value of the
proton will depend upon how long the proton
is residing in that particular chemical environment.
If it is residing for example long enough
then NMR will be able to tell the chemical
environment to be either axial or equatorial.
If it is too short, then also NMR probably
will give an average value of the equatorial
and the axial chemical environment positions.
Typically the difference between the two states
of residence is very small of the order of
micro calories per mole. Therefore, the lifetime
in any particular state should be sufficiently
long enough in the NMR time scale to give
the correct chemical shift value. The uncertainty
principle is expressed here. Now this is the
uncertainty principle expressed in terms of
the residence time or the lifetime in a particular
state and the difference energy between the
two states. So, let us say for example, the
axial and the equatorial states of particular
hydrogen that has being present here. There
can be a very large uncertainty in the energy
state depending upon the lifetime of the molecule
in that particular state.
So, the NMR signal can be either very sharp
or very broad depending upon 2 types of conditions
that is met. What are the 2 types of conditions,
if the protons is exchanging between the two
states very rapidly, then NMR will only see
an average chemical shift value of the two
states the signal can still be will very sharp
signal in this particular case nevertheless
it will an average chemical shift of the 2
states. If the proton is exchanging between
the two states very slowly in the NMR time
scale, the NMR will give only the individual
chemical shift values of the 2 states. In
other words, NMR can distinguish the hydrogen
to be either in the axial state or in the
equatorial state in the case of cyclohexane.
So, 2 signals will be obtained one corresponding
to the axial and other one corresponding to
the equatorial stage.
Now in between these two states neither too
fast or nor too slow, the uncertainty will
set in terms of the determination of the chemical
environment of the particular proton. As a
result of that in between states where the
rate process is neither too high nor too slow,
there will be a large uncertainty broadening
up the signal is what one typically sees in
the variable temperature NMR spectra. Now,
what makes the variable temperature NMR a
very special technique? Because chemical rate
process can be controlled by temperature the
rate of a reaction can be controlled by a
temperature and hence the usefulness of the
variable temperature NMR spectroscopy.
Now, let us take the first example of the
study of dynamic processes, which are based
on conformational dynamics of molecules.
A very classical textbook example is the chair
to chair interconversion of cyclohexane. This
has been studied thoroughly by NMR spectroscopy.
In order to study this process, the cyclohexane-d11
was taken. In other words there is only 1
proton that is present in the cyclohexane,
all the other proton has been substituted
with deuterium. So, depending upon the kind
of chair conformation that cyclohexane has
it either in the axial position or it is in
the equatorial position. Now this study has
been carried out by variable temperature NMR
spectrum. The spectra are shown on the left
hand side in this particular frame here. If
we look at the NMR spectrum at minus 50 degree
Celsius for example, which is already a low
temperature process. NMR is unable to distinguish
between the axial hydrogen and the equatorial
hydrogen, what you see is only one signal
corresponding to the average of the 2 states
namely the axial state as well as in the equatorial
state. In other words even at minus 50 degrees
Celsius the rapid interconversion is taking
place and in the NMR times scale NMR is enable
to distinguish whether the hydrogen is residing
in the axial state or in the equatorial state.
What it gives is an average signal corresponding
to neither of the states of the hydrogen being
present in the either axial or in the equatorial
position.
Now, let us go to the other extreme when that
sample is cool to minus 89 degree Celsius
for example. What happens is you see two signals
corresponding, one corresponding to equatorial
state of the hydrogen which is at the higher
delta value, this is about 1.6 delta ppm in
terms of the chemical shift value, and the
other one which is coming at a lower delta
value corresponds to the axial position hydrogen
which is about 1.2 delta ppm or so. Now at
this particular temperature, the interconversion
of the 2 states is so slow that NMR is able
to distinguish this particular conformer as
the axial conformer, and this particular conformer
as the equatorial hydrogen conformer corresponding
to the two states.
Actually there is no energy difference between
the two states the axial and the equatorial
or essentially the same chair conformation.
So, they should exist in equal population
of one is to one ratio, and you can see from
their height of the peak both the peaks are
nearly equal in intensity. Therefore, the
area under each of the peak is going to be
approximately same. So, one is one mixture
of the conformation where in the hydrogen
is in the axial position, and another conformation
where in the hydrogen is in the equatorial
position corresponds to the two line that
one sees in the spectrum. Anywhere in between
the temperature, there is a large uncertainty
as to whether the hydrogen is existing in
the axial position or in the equatorial position,
NMR is unable to distinguish between the two
positions. And hence there is a large uncertainty
associated with the measurement of the chemical
shift which is reflected in terms of broadening
of the signal.
Now, between minus 63 and minus 60 you can
see there is a coalescence that is taking
place. There are two peaks here which coalesces
to only one peak at this particular temperature.
So, this particular temperature is known as
the coalescence temperature. The coalescence
temperature is important, because several
kinetic parameters can be obtained from the
coalescence temperature. And above the coalescence
temperature of course, you see an average
signal of only if you take the chemical shift
value of this, this will exactly the arithmetic
average of this two chemical shift values.
In other words, you can see that it comes
at midpoint corresponding to this particular
chemical shift to chemical shift value, midpoint
is corresponding to this particular chemical
shift and that is a average value of the axial
equatorial conformation equilibrium being
very rapid.
Now, let us take the example of the carbon-13
spectroscopy of 1,2-dimethylcyclohexane particularly.
The cis isomer of 1,2-dimethylcyclohexane
should have one axial methyl group and one
equatorial methyl group. Both the axial and
equatorial methyl group point in that same
direction, and hence it is a cis isomer. If
you want to refresh your memory about the
dynamics of the cis isomer of the 1,2-dimethylcyclohexane,
please refer to book on stereochemistry of
organic compounds. Now this particular molecule
is a chiral molecule, and it does not have
any kind of symmetry elements that is present
here. Therefore, if this molecule were to
exist in this particular form then all the
carbons that are present in this molecule
should be distinguished chemical shift wise
and there should be 6 of the ring hydrogen
so sorry ring carbons and 2 of the methyl
carbons which are also chemically distinct,
one is axial and the other one is equatorial.
So, one would see 8 signals in the carbon-13
NMR spectrum of such a molecule. Now what
is a dynamic process that is taking place
the dynamic processes is establishment of
this equilibrium of one chair form going to
another chair form. In the process, actually
what happens is one of the enantiomer gets
converted to the antipode of the enantiomer.
In other words, this is a processes of racemization.
Cyclohexane 1,2-dimethyl cis isomer of 1,2-dimethylcyclohexane
is an example where it is a non resolvable
chiral molecule, non-resolvable because it
is rapidly undergoes a racemization by going
from one chair form to another chair form
which is a racemization processes itself.
Now while going through this transformation
it has to go through a transition state which
look very similar to the planar transition
state. In other words, this chair form has
to go to this particular chair form. At some
point of time, in the transition state has
to sort of attain a planarity kind of a structure
which is this particular structure and this
structure has a plane of symmetry as you can
see this molecule. So, this would be an a-chiral
system where as these 2 conformation would
be chiral in nature.
Now, let us look at the carbon-13 spectrum.
This is the DEPT spectrum, in other words
in this particular spectrum the CH2 carbons
will come as negative peaks and the CH and
the CH3 carbons will come has positive peaks
in terms of the phase of the peak that is
being seen you can have a negative phase or
the positive phase. Depending upon whether
it is a CH2 in which case it is a negative
phase or if it CH or CH3 odd number of hydrogen
being present then it would be a positive
phase of the NMR signal. So, as I said if
this molecule were to be existing in a frozen
state without the conformational interconversion,
there will be a 1:1 ratio of mixture of these
2 isomers which are enantiomers. Enantiomers
are indistinguishable by NMR spectroscopy,
they are chemically equivalent. So, their
chemical shift value of this axis equatorial
carbon and the this equatorial carbon will
be identical. So, one should see eight signal
in the NMR spectroscopy of which four of them
will be CH2 type of carbon, two of them will
be CH carbon, and two of them will be CH3carbon.
So, if you see four signal which are in the
negative phase one 2, 3, 4 these 4 signals
correspond to the CH2 and two of the CH and
two of the CH3 will have positive phase 1,
2 these are probably the CH carbons and these
are the CH3 carbons. So, there are 8 signals
that are seen in the NMR spectrum carbon-13
spectrum of the cyclohexane. So, variable
temperature is measured in the carbon-13 NMR
spectrum of dimethylcyclohexane in this particular
case. This is the normal carbon-13 spectrum
whereas, this is the DEPT spectrum the depth
spectrum is essentially recorded to distinguish
between the CH2, CH and CH3 carbons. If you
look at the normal carbon NMR spectrum also,
you will see 8 signal 1, 2 another signal
is merged with this 3, 4, 5, 6, 7th one is
again merged it is not resolved so 7, 8. There
are 8 signals that are very clearly seen in
the NMR spectrum.
Now let us assume that this is sort of not
frozen, it is undergoing a rapid interconversion
between these 2 states. If it is going to
rapidly inter convert between the 2 state
the NMR is going to see the molecule as if
this is a state that is being present, because
this is very similar to a transition state
structure between the 2 structures that are
mentioned here. So, if NMR sees a signal corresponding
to a structure of this kind where there is
a planar symmetry, then you should see only
half the number signals in the NMR spectrum
that is 1 signal corresponding to the CH3
here, which will be identical to this CH3.
One signal corresponding to this CH and this
would be essentially identical to this CH,
one signal corresponding to these CH2 and
one signal corresponding to these CH2. Indeed,
when look at the spectrum at room temperature,
where there is a rapid interconversion of
one conformer and the other conformer. NMR
is enable to distinguish the axial equatorial
methyls. So, the methyls gives just only one
peak in the NMR spectrum which is shown here
for example.
So, the NMR spectrum should see 1, 2, 3, 4
only 4 signals should be seen. So, indeed
only 4 signals are seen in the high temperature
NMR spectrum. What do I mean by high temperature
is at room temperature where the rapid interconversion
is taking place. At low temperature or let
us say for example, 223 kelvin or so, the
interconversion is slowed down considerable
such that NMR is able to see the axial equatorial
methyl separately and the conformation gives
this is a chiral conformation, so eight different
signals are seen in the NMR spectrum. So,
the molecule is a beautiful example of essentially
a chiral molecule existing in 2 enantiomeric
forms. An enantiomeric being indistinguishable,
you just to see as if there is only one type
of molecule in the NMR spectrum of the cis
dimethylcyclohexane 1,2-dimethylcyclohexane
at low temperature. Whereas, at room temperature
close to room temperature essentially you
see the average signal corresponding to 4
carbons in the NMR spectrum, because this
would be the average of these 2 type of structures
that you have in the NMR spectrum.
Now, at the coalescence temperature, one can
find out what is the rate constant of the
. The rate constant at coalescence temperature
is given by this expression where k which
is kc is the rate constant at the coalescence
temperature which corresponds to pi delta
nu. Delta nu is the difference between the
chemical shift values of the 2 type of system,
if it is a axial hydrogen and equatorial hydrogen
delta nu corresponds to the difference between
the chemical shift value of the axial hydrogen
and the equatorial hydrogen divided by root
2. So, we can do a one point kinetics and
get rate constant at the coalescence temperature
using this expression provided there is no
spin-spin coupling between the 2 protons.
If there is a spin-spin coupling between the
2 side exchangeable proton then the coupling
constant also gets into the expression. So,
at this point of time, the kc would correspond
to this particular expression that is given
here. Now once you have kc at the coalescence
temperature, one can also calculate the thermodynamic
parameter in terms of the activation energy
of that particular process using this expression,
using the NMR technique, which would be a
one point kinetic technique.
Let us take another example of a chair-to-chair
interconversion. It is not only cyclohexane
that undergoes chair-to-chair interconversion.
This kind of heterocyclic system where you
have X is equals to oxygen or sulphur. In
other words it is 1,3,5 trioxane or 1,3,5-trithiane
kind of molecules also undergo rapid interconversion
from one chair form to another chair form.
In the chair form interconversion is denoted
by the axial hydrogen being red here, which
becomes equatorial upon chair-to-chair interconversion.
And the equatorial hydrogen being blue here
which gets converted into the axial hydrogen
during the chair-to-chair interconversion.
Now, under the conditions are very slow exchange
between these 2 molecules the NMR spectrum
is going to be seen as a single spectrum of
this particular molecule. The axial and the
equatorial hydrogen are attached to geminal
to this particular carbon, so they are going
to be diastereotopic in nature, so they would
couple with each other. So, this coupling
correspond to AB quartet kind of a signal
in the NMR spectrum of such molecule.
In fact, this axial hydrogen is same as the
axial hydrogen over here and the axial hydrogen
over here the molecule as C3 axis of symmetry.
So, it does not matter which one of the methylene
in groups that you take for analysis. Essentially
you will get an AB pattern at low temperature.
At room temperature, when it is rapidly inter
converting between the 2 states of course,
one cannot distinguish between the axial and
the equatorial hydrogen, so essentially one
gets only a singlet kind of an NMR spectrum
at the room temperature or at a higher temperature
where the rapid interconversion is taking
place. Now, based on the variable temperature
NMR study in case of 1,3,5-trioxane molecule
the barrier for the flipping of one chair
conformation going to the another chair conformation
is very similar to the one that you for cyclohexane
namely 10.9 kilo calories per mole. In fact,
in the cyclohexane case the 10 kilo calories
per mole activation barrier is probably the
most precise value that is ever determined
using a spectroscopy technique for such a
conformation dynamic processes.
Now, let us take the example of piperidine
as a molecule. In the case of piperidine,
the 3 position and the 5 position are deuterated.
In other words substituted by deuterium, so
that one can avoid the complication of coupling
between these hydrogen and these hydrogen
here in the NMR spectrum. So, what is present
here is methylene group in the 2,6 positions
and another methylene group in the 4 position
that is present in the molecule. Now this
is the methylene region of the NMR spectrum
of piperidine molecule. And you can see here
at a very low temperature of minus 85 degree
Celsius or so, there are 2 AB quartet seen
here, 1 AB quartet has nearly twice the intensity
of the other AB quartet. In fact, if you look
at the hydrogen which are in the 4 position
this would appear as an AB quartet at low
temperature when there is not a rapid interconversion
between the 2 states. Similarly, when you
look at the hydrogens in the 2, 6 positions
of this molecule also, you would see only
a AB quartet corresponding to 4 hydrogen intensity
that is the reason one of the AB quartet is
twice as big as the AB quartet. So, this AB
quartet which is in the 4 position which is
away from the nitrogen has a lower chemical
shift value. Whereas, the one that is adjacent
to the nitrogen has a higher chemical shift
value which is this particular AB quartet.
So, you see two AB quartets corresponding
to the diastereotopic methylene kind of a
proton; in a frozen state where there is no
rapid interconversion between the chair-to-chair
interconversion between the two states. Now
what happens if we heat the sample up to about
minus 40 degree where the rapid interconversion
starts to take place the two AB quartet essentially
collapse, because you can no longer distinguished
the axial and equatorial position when it
is rapidly undergoing interconversion from
one chair form to the other chair form. So,
this AB quartet collapse is to a singlet,
this AB quartet also collapse us to a singlet.
This corresponds to the 4 hydrogen in the
2 and 6 position, this corresponds to the
2 hydrogen in the 4 position which are these
2 hydrogen in this molecule.
Now such a dynamic process can also be simulated
using computer simulation by putting in appropriate
rate constants for the processes. And essentially
one can simulate not only the low temperature
and high temperature spectrum, the line broadening
at the intermediate levels can also be precisely
simulated in the NMR spectrum and these are
simulated NMR spectra and this corresponds
to the experimental NMR spectra at various
temperatures. Now, we can go from here for
example, at low temperature, as you increase
the temperature at one particular point, there
is a coalescence temperature which is close
to about minus 62.5 degree Celsius or so in
this particular case and that coalescence
temperature the AB quartet essentially coalescence
to a single peak. It is somewhere between
minus 60 and minus 62.5 degree Celsius or
so, in this particular instance.
These are examples of simple carbon-carbon
rotation or restricted carbon-carbon rotations
which can be studied at low temperatures.
Now normal temperature if we look at the tertiary
butyl cyclopentane, there will be a rapid
rotation between this carbon and this carbon.
So, one will not able to distinguish the three
methyl groups of the tertiary butyl group
at ordinary temperatures. However, if the
sample is cool to minus 150 degree Celsius,
it is possible to freeze the molecule from
undergoing rapid interconversion of conformation.
This is a Newman projection formula of this
3 carbons that are seen here. In other words,
this carbon is in the front and this carbon
is in the back side of the Newman projection
and the hydrogens are clearly shown of the
cyclopentane ring and the hydrogen that is
attached to this particular carbon is coming
here.
Now if you look at this particular picture,
this is actually the gauche conformation or
the staggered conformation of this carbon-carbon
bond rotation. Now if the carbon-carbon bond
rotation is frozen, this is likely to be the
most stable conformation because the bulky
groups are far away from each other in terms
of the position of the bulky groups. If that
were to be the case these 2 methyl group should
have a chemically identical environment and
this chemical this particular methyl group
should have a different chemical environment
in comparison to the other 2 methyl groups.
So, a sample measured at a very low temperature
of minus 150 degree Celsius has 2 singlet
in the ratio of two is to one, one corresponding
to this particular methyl groups, which are
these 2 methyl group with a intensity of two,
and this particular methyl group come separately
with the intensity of one because this has
6 hydrogens, these 2 methyl group and methyl
group has 3 hydrogen that is why the intensity
ratio two is to one
Now, let us take the example of 2,2,3,3-tetrachlorobutane
n-butane for example. Here the chlorine groups
are fairly bulky groups. So, one can freeze
the rotation of this particular molecule,
the carbon 2, carbon 3 bond rotation can be
frozen. Under these conditions, if you look
at very low temperature NMR spectrum, these
are probably the 2 confirmations which are
going to be the most populated conformation
in the among the various conformations that
are possible, because these are the two conformers
which are staggered conformation. Now if we
look at this conformation alone, the 2 methyl
groups are chemically identical environment,
they are not distinguishable because they
are flanked by 2 chlorines in each case. So,
if you measure the spectrum of this molecule
alone then there will be only one signal for
the 2 methyl group.
Similarly, if you measure the NMR spectrum
of this conformation alone, there is a C2
axis of symmetry bisecting this molecule in
this particular way. So, this 2 methyl groups
are changeable by C2 operation. Therefore,
they are chemically identical in their environment,
but the chemical environment around of this
2 methyl groups are very different from the
2 methyl groups here. Here the methyl groups
are flanked by 2 chlorines, whereas here one
is flanked by a chlorine the other one is
flanked by a methyl group. So, chemical shift
wise, although these 2 are identical, these
2 are different from the other 2 which is
in the other confirmation. In other words
the methyl group in this conformation have
a different chemical shift environment compared
to the methyl group in this particular conformation.
If these 2 conformations are the most populated
conformation at very low temperature, then
this should be even more favorable because
the 2 methyl groups are anti where this 2
methyl groups are gauche with respect to each
other. So, at low temperature of minus 44
degrees Celsius 2 singlet resonances are seen
in this particular spectrum corresponding
to two is to one ratio. In other words, this
conformer population is twice as much as the
conformer population which is correspond to
this one. The activation barrier for the carbon-carbon
bond rotation in this molecule is calculated
to be about 15 kilocalories per mole. One
can use various nuclei for the variable temperature
NMR spectrum we have already seen one example
of the carbon nuclei being used in the variable
temperature NMR spectrum of the cis 1,2-dimethylcyclohexane.
Here fluorine nucleus is used for the conformational
study of this difluoro dibromo dichloroethane
derivative.
Now if you look at this various conformations,
the one where the 2 bromines which are the
bulky groups in this particular system which
are the farthest away from each other in this
particular conformation. In other words conformation
A is going to be the most stable conformation,
conformation B and C are going to be the least
stable conformation of which for example,
C is going to be the least stable because
the 2 bulky groups which are bromine and that
2 chlorine groups which are also bulky with
in comparison to the 2 fluorine for example,
this will be the least preferred conformation
and this will the most preferred conformation.
The barrier to go from A to C has been calculated
using the fluorine NMR spectroscopy. The fluorine
NMR spectrum, if you measure the spectroscopy
at very low temperature, you can see one signal
corresponding to these 2 fluorine, one signal
corresponding to these 2 fluorine, and one
signal corresponding 2 these fluorine here
which are chemically distinguishable from
one to another in terms of A, B, C being chemically
distinguishable. The activation barrier to
go from A to C has been calculated by the
variable temperature NMR to be about 9.9 kilo
calories per mole.
These are some exotic examples of fluorine
NMR being used for the fluorine 19 has an
isotope which is a spin half isotope. So,
it is just like a proton spectroscopy that
we are talking about. Spin half nucleus is
what we are talking about. There are 2 isomers
possible for this 1,2-disubstituted derivative
or this time this is a large macrocyclic rings,
so it should undergo a rapid conformational
change because of the size of the ring is
fairly large. And these 2 fluorines are in
the erythro isomer and this 2 fluorines and
in the threo isomer as it is in the erythro
and threo the 2 fluorines are not distinguishable
they are nearly identical chemical environment
with respect to each other.
So, at room temperature when you measure the
spectrum where this undergoes a rapid interconversion
with among the various confirmation NMR would
be able to distinguish between this 2 fluorines
being either axial or equatorial in this particular
macrocyclic system. So, it essentially gives
only one signal for the threo and one signal
for the erythro for the 2 fluorine atoms,
and this is essentially seen at room temperature.
When you cool it to very low temperatures
of minus 75 in the case of the erythro and
minus 92 in the case of threo the signal splits
into 2 singlet, 2 singlet because these 2
fluorines are now distinguishable with respect
each other. So, one can see 2 fluorine separately
one probably corresponds to an axial kind
of a position, the other one corresponds to
an equatorial kind of a position. Similarly
in this molecules also the 2 fluorines becomes
distinguishable and that is the reason you
see 2 signals here.
This has been theoretical calculated as the
number of various conformations that are present
in this molecule. If you look at this particular
conformation, where the 2 fluorines are given
the the sayan color the 2 fluorines are indicated
by the sayan color. In this conformation,
the 2 fluorines have chemically different
environment and this is a most stable in terms
of the relative energy being zero kilocalories
per mole. This is 2.81 kilo calories higher
energy compare to this 3 conformation one
is about 3.7 2 kilo calories higher energy
compare to conformation three. So, in conformation
three, the 2 fluorines are different and that
is why at low temperature one sees this 2
fluorine separate signals. At room temperature,
there is rapid interconversion among the various
conformation. So, the 2 fluorines become indistinguishable
at the higher temperature. Same is the case
with the kind of the threo isomer also; the
2 fluorines have distinctly different chemical
environment at low temperature. This is a
lowest conformation energy compared to the
other conformers this would be highly populated
at low temperature. So, the 2 fluorines are
different in chemical environment. So, 2 signals
at low temperature at high temperature or
at room temperature there is rapid interconversion
of this various conformers. So, the 2 fluorines
become indistinguishable. As a result there
is only one signal that is present in the
high temperature NMR spectra.
Now, this is a propeller shaped molecule,
this is called a tryptophan sorry triptycene
not tryptophan this molecule is call triptycene,
and this is a propeller shaped molecule for
example. In this molecule, when you put a
substituent here that substituent is hindered
from rotating freely by this 3 hydrogens which
are indicated. In other words cartoon representation
of this molecule is shown here. This is a
conformation of the molecule you can see very
clearly that in the nitrogen substituent that
is present in this cavity the free rotation
of the nitrogen is going to be hindered by
the bulky groups that are being present in
the nitrogen interacting with this 3 hydrogen
which occupy this positions. So, the rapid
rotation of the carbon nitrogen bond is not
possible in this molecule that is one process.
The second process is the nitrogen can also
undergo inversion pyramidal inversion, the
lone pair is down here the lone pair can also
become up by the pyramidal inversion. So,
this is essentially a propeller shaped molecule
where the carbon-nitrogen bond as restricted
rotation in this molecule.
This has been studied by NMR spectroscopy.
Now if you look at this molecule this would
be a chiral molecule, if this is conformationally
frozen in this particular state, the reason
being there is no planar symmetry or there
is no Sn symmetry present in this molecule.
So, as it is the molecule is chiral in the
frozen conformation like this, when there
is no rapid carbon nitrogen bond rotation.
So, this 2 CH2 hydrogens, these 2 hydrogens
on the CH2 become diastereotopic in nature.
So, we are looking at this CH2 hydrogen of
this molecule; at low temperature when there
is no rapid rotation of the carbon hydrogen
bond because of the chiral environment that
is present in this molecule. The CH2 appears
as an AB quartet because CH2 is a diastereotopic
hydrogen in this particular system.
When this becomes rapidly inter converting
in terms of the carbon nitrogen bond rotation
being very high at a higher temperature; in
other words at minus 49 degree Celsius or
so that carbon-nitrogen bond becomes rotatable
easily. At those temperatures, the CH 2 is
no longer distinguishable and is suggest to
see a singlet for the CH 2 hydrogen in this
particular molecule. And this is simulated
spectrum putting in this rate constants corresponding
to various temperatures. One could easily
simulate the spectra that is shown in the
experimental side which is this side and this
is a simulated spectrum. Based on the variable
temperature NMR spectrum the activation barrier
for this particular process has been given
in this table as 11.6 kilo calories per mole
for the n benzyl derivative and for the n
methyl derivative is about 9.24 slightly smaller
when that is a n methyl group in this system.
One can also look at it from the carbon-13
NMR spectroscopy point of view, these are
the quaternary carbons labeled as QC there
are 3 quaternary carbons in the front one,
2 and 3 these are the quaternary carbons.
The back side also there are 3 quaternary
carbons, which are aromatic carbons one, 2
and 3 if this molecule is truly chiral at
low temperature one should be able to see
this 3 carbon separately, and the backside
3 quaternary carbons also one should be able
to see it separately. So, this is what happens
at low temperature when the spectrum is shared
at minus 168 degree Celsius. There are 6 carbons
that are seen corresponding to carbon number
one, carbon number two, carbon number 3 which
is in the front; carbon number four, carbon
number five, carbon number 6 in the back side
which essentially constitute the 6 lines that
you see in the carbon-13 spectrum of this
particular compound. If the molecule is undergoing
a rapid rotation and the chirality is lost
as a result of that then all the 6, 3 carbons
in the front and the 3 carbons in the back
should come as single signal. So, essentially,
you see two signals, one corresponding to
the carbons in the front the other one corresponding
to the carbons in the back side of the molecule
which are these three carbons which are present.
When the chirality is removed by putting 2
identical groups on the nitrogen. This is
a N,N- diethyl group where as the previous
examples is N-methyl N-benzyl group and that
is what make this molecule chiral a chirality
is removed now. So, essentially what you see
is the 2 methyl groups sorry the 2 hydrogens
on the methyl group essentially appearing
as a simple cortex in this particular case.
And when these molecule is in frozen state,
there are 2 conformations possible; the methylene
group can be either in this position or it
can be in position also. So, 2 different environment
is what do seen for the methylene which is
seen by the 2 humps that are seen, it is not
at fully this temperature is not low enough
for example, to completely freeze out the
molecule. So, that is why you see broadening
up the line.
If it is possible to measure the spectrum
even at low temperature perhaps one would
see 2 quartet kind of a system is what one
would see in this particular case. So, the
2 methylenes become indistinguishable and
become a single signal at high temperature;
at low temperature these 2 methylenes are
possible to distinguish from one another because
of the pyramidal inversion that is taking
place. So, activation barrier for this process
is about 8.1 kilocalories per mole for the
rotation of the carbon nitrogen bond in this
molecule.
Here is another very interesting example of
an [18] annulene molecule. Please recall the
anisotropic effect of aromatic ring current
effect. This is an aromatic molecule because
it is an [18] annulene molecule corresponding
to (4n+2) electrons system. Now, there are
6 hydrogens in the cavity of the molecule
and there are twelve hydrogens on the periphery
of the molecule. So, if this is truly aromatic
and planar in nature this 6 hydrogen should
be highly shielded because they come in the
shielding zone where as these twelve hydrogen
should be highly deshielded because they come
in the deshileding zone of the ring current
effect of an isotropic this particular molecule.
However, the molecule is big enough to undergo
conformational change. In other words, if
you rotate this carbon-carbon single bond
this hydrogen can be brought in and this hydrogen
can be taken out. So, the hydrogens which
are originally inside can go out, and the
hydrogen which are originally in the outside
periphery can also come inside 6 at a time.
So, there is possibility of a rapid interconversion
between the inside hydrogens and the outside
hydrogen.
So, if such a process is taking place very
rapidly, the NMR would not be able to distinguish
between the hydrogens which are inside and
the hydrogens which are outside. In fact,
when the spectrum is measured at plus 110
degree Celsius, a sharp singlet is what is
seen in the molecule for all the 18 hydrogen,
there are no other hydrogens which are distinguishable
in this molecule. The inside outside process,
in and out process is what is taking place
rapidly by carbon-carbon bond rotation. So,
as a result ones see all the eighteen carbon
as a singlet in this particular system.
Now see what happens at low temperature when
the spectrum is measured at minus 60 degrees
Celsius, but minus 60 the molecule is frozen
and it is probably in the planar most stable
conformation because it is an aromatic system.
If it is non planar of course, it will not
be aromatic. In fact, it a probably goes through
a non planar transition state when it is undergoing
a rapid interconversion of the inside hydrogens
going out and the outside hydrogens coming
in. Now at the very low temperature, when
the molecular conformation is frozen in this
particular fashion, the inside hydrogens can
be very clearly seen at minus 3 delta ppm
which is this signal here as a multiplet,
and the outside hydrogen which are the 12
hydrogen can also be seen around 9.5 ppm or
so delta. So, this is a highly deshielded
hydrogen aromatic hydrogen; this is a highly
shielded hydrogen which is also aromatic,
but it is in the core of the aromatic unit
in this particular case.
Now, there are 12 hydrogens in this particular
multiplets and the 6 hydrogen in this particular
multiplets. So, one has to take arithmetical
average of the the statistical average of
this 2 not the arithmetical average, the statistical
average of this 2 chemical shift values attain
the chemical shift value of the average doubt
signal which is this particular signal. In
between, we can see there is a large uncertainty
associated with the determination of the chemical
shift value; particularly, if you look at
plus 40 degree Celsius the uncertainty so
much that you do not see any signal also.
You just see a flat line NMR for this particular
spectrum for this particular compound and
uncertainty so much so that you do not see
any signal at plus 40 degree. This is a scenario
which is an interesting scenario that you
measure in NMR spectrum and you do not see
a signal insight of the fact there is a sample
that is present because of the uncertainty
principle essentially wipes out the signal
to be a flat line in this particular case.
Another example, a very similar example to
the cyclohexane system that we talked about.
This is a this is a cycloalkyne is a strained
system. The molecule is not planar as it shown.
The molecular conformation is a C2 symmetry
conformation which is the chiral conformation.
The molecule can undergo C2-C2 kind of a this
is also C2 symmetry and this is also C2 symmetry
and they are mirror images of each other they
can undergo rapid interconversion by this
carbon coming down, and this carbon going
up which is the conformational change that
we are talking about in this case. And such
a conformational change would make the molecule
look like this one in the transition state.
If it were to this conformation, this as a
planarity associated plane of symmetry associated
with the molecule. So, this is a chiral transition
state. So, at 145 degree Celsius for example,
this molecule sort of NMR point of view looks
like this and all the methylene hydrogen are
equivalent, so you essentially get a singlet
at high temperature.
At low temperature, if it has to be a chiral
conformation like this, these 2 hydrogen will
be diastereotopic because this is a chiral
molecule, so diastereotopic hydrogen. These
are enantiomers which are indistinguishable
nevertheless within the enantiomer one of
the enantiomer, this CH2 will be a diastereotopic
hydrogen which is identical to this CH2 because
of the C2 symmetry. So, such a diastereotopic
hydrogen gives AB quartet which is nicely
seen at 58 degree Celsius or so. So at room
temperature, when you measure the spectrum
this is what you are going to see essentially
AB quartet for this molecule because it is
a chiral conformation that we are dealing
with in this particular case.
This is another standard textbook example
of a restricted carbon-nitrogen bond rotation
in amides n m dimethyl form amide is discussed
here. Now because of the participation of
the nitrogen lone pair delocalization onto
the oxygen, the molecule attains a sort of
a double bond character between the carbon-nitrogen
bond because it has a double bond character,
it activation barrier for free rotation is
fairly high. So, this molecule does not undergo
free rotation at room temperature. Activation
barrier calculated from the variable temperature
NMR spectrum is about 22 kilocalories per
mole. So, at room temperature, this molecule
can be giving 2 signals corresponding to the
red methyl and the blue methyl; the red methyl
is cis to the oxygen, the blue methyl is trans
to the oxygen; chemical shift environment
wise this will be different from this particular
methyl group. So, as a result of that this
molecule essentially under the conditions
of room temperature will give 2 signals for
the 2 methyl groups and you see 2 signals
at room temperature around 35 degrees you
see 2 signal. One that is next to the oxygen
cis to the oxygen probably this particular
signal; one that is trans to the oxygen is
probably this particular signal here.
And if it is undergo rapid interconversion,
this 2 methyl groups will interchange it is
place the blue now has become the cis to the
oxygen, and the red has become the trans to
the oxygen. If such a rapid interconversion
wise to take place the coalescence will take
place and the 2 methyl will essentially appear
as a singlet. In fact, at 170 degree Celsius
the molecule shows a singlet for the two-methyl
groups. So, because of the restricted rotation
having this kind of a barrier you have to
heat up this sample to high temperature before
coalescence can take place. So, coalescence
temperature is roughly 123 or so, because
you can still see 2 peaks in this region here
at 180 degree eighteen degrees. So, the coalescence
takes place around 120 or so, which is corresponding
to the coalescence temperature. Above the
coalescence temperature, you have a sharp
singlet; and below the coalescence temperature,
you have 2 signals corresponding to the 2
methyls which are indicated by color coding.
Here is the last example of this particular
lecture. We are talking about again a restricted
rotation of the carbon-nitrogen bond. This
is a trinitro N-methylaniline is the molecule;
trinitro N-methylaniline they are 2 hydrogens
in the aromatic unit. Suppose, if there is
a restricted rotation around the carbon-hydrogen
bond, if the molecule can be represented like
this then this 2 hydrogen are no longer in
the same chemical environment, it should be
possible to distinguish them. And if there
is a coupling between these 2 nitrogen which
is a meta coupling. So, this these should
doublet and this also should be doublet due
to the meta coupling in this particular molecule.
However, if there is a rapid rotation of the
carbon nitrogen-bond, these 2 hydrogen chemical
environment will average out it will give
only a singlet. Indeed at room temperature,
you do see only a singlet that at very low
temperature when there is a restriction of
the carbon-nitrogen bond rotation this methyl
group in this nitrogen makes this hydrogen
and this hydrogen distinguishable chemically.
So, what you see is an AB quartet corresponding
to the meta coupling between the AB system
which is this coupling that we are talking
about. This is a simulated spectrum based
on the computer simulation, using this kind
of a time lifetime of this molecule for the
various rotational rate constant is what is
the inverse of this will be the rotational
rate constant of the process that we are talking
about. So, we are not done with the dynamic
processes of NMR. In the next module also,
we will continue with the dynamic process
of frictional molecule and certain organic,
organometallics examples of the molecular
dynamics by variable temperature NMR. So,
see you in module-14 and continue with this
lecture in that particular module.
Thank you very much.
