Advanced FTNMR Techniques

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Advanced FT-NMR Techniques

• CHEM 430
• Fall 2009

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Example Problem 1

• Use the MS to provide MW and the presence of the
  most common halogens or odd of nitrogens
• Couple the M1 data for isotopic 13C with the 13C
  NMR spectrum to deduce the actual number of
  carbon atoms
• Identify all functional groups by FT-IR
• Use a brief survey of the 1H NMR to determine
  nature of compound- aliphatic, aromatic or both,
  as well as the depth of the problem

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Sample Problem 1
M 114, M1 non-existent
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Sample Problem 1

• With the availability of 1H NMR dont bother with
  Rule of Thirteen or HDI calculations at this
  point
• Make the same basic observations you would if the
  MS was your only data
• This compound must/probably
• Have less than 9 carbons
• Not have any Cl or Br atoms
• Not be aromatic
• Contain an even of nitrogen atoms

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Sample Problem 1

• Inspect the FT-IR for functional groups
• Concentrate on heteroatom groups that would NOT
  show on 1H NMR! Ignore alkane, alkene, alkyne
  and aromatic for now

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Sample Problem 1

• Note the strong CO band in the high 1700s
  remember this is most likely ester, anhydride or
  acid halide but could be a strained ketone
• We can rule out anhydride (only one CO band) and
  acid halide (no Cl, Br by MS) presence of
  strong band at 1180 could support ester

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Sample Problem 1

• Initial Inspection of 1H NMR

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Sample Problem 1

• Initial Inspection of 1H NMR
• Molecule not aromatic or alkene (confirms MS)
• Primarily aliphatic with 3 families of protons
  close to an EWG
• 7 families of protons as clean multiplets are
  observed
• Integration suggests1211113 ratio and a
  total of 10 hydrogens

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Sample Problem 1

• Initial survey is complete
• Molecule is an aliphatic ester with less than 9
  carbon atoms and 10 hydrogens approximate
  formula Clt9H10O2
• Now the problem is to complete what we previously
  could not with IR, MS and UV data to figure the
  bulk structure of this compound

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Sample Problem 1

• Now inspect the 13C NMR in conjunction with the
  DEPT-135 spectrum

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Sample Problem 1

• From the 13C spectrum we observe 6 signals
• We also confirm the CO is an ester
• To test to see if there are chemically equivalent
  carbons use the MS M data
• Formula is now C6H10O2 which has a MW of 114
• HDI is 2 which suggests a ring is present as well
  as the CO

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Sample Problem 1

• From the 13C DEPT-135 we observe that 5 signals
  remain (less CO)
• We observe 3 negative peaks or 3 CH2s the other
  two must be CH3 or CH
• The downfield carbon is not CH2-, this is the
  carbon next to the sp3 oxygen of the ester
• Keep in mind the presence of a ring means this
  compound may not end in a CH3
• HDI is 2 which suggests a ring is present as well
  as the CO

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Sample Problem 1

• Remember to never stop playing with the
  mathematical bounds of the molecule
• If three carbons are CH2- that is six protons
• We observed a total of ten by 1H NMR and we have
  two remaining C signals - one must be a CH the
  other must be a CH3!
• Now we know the pieces that must be put together!

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Sample Problem 1

• Here is what we have
• -(CO)-O-
• -CH3 -CH2- -CH2- -CH2- -CH
• We also know there is a ring closure

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Sample Problem 1

• We now use the first of our advanced 2-D
  techniques
• 1H-1H COrrelation SpectroscopY or COSY
• This experiment allows us to see what protons are
  coupled to which other protons

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2D COrrelation SpectroscopY

• DESCRIPTION The 2D COSY experiment is the most
  simple and widely used 2D experiment.
• It is an homonuclear chemical shift correlation
  experiment based on the transfer polarization by
  a mixing pulse between directly J-coupled spins.
• Thus, homonuclear through-bond interactions can
  be trace out by simple analysis of the 2D map
  providing a more general and more useful
  alternative to classical 1D homodecoupling
  experiments.

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2D COrrelation SpectroscopY

• The basis for this experiment
• As with any 2-D technique we use a pulse
  sequence
• By varying the t1 time, we allow the prepared
  protons to transfer their spin to their neighbors
• By exciting this population with another pulse
  and obtaining the FT we will observe the protons
  that are coupled
• For each individual t1 we take an 1H NMR, each
  will be transformed in the normal direction
• Across the array of t1 we can take Fourier
  transforms and obtain the cross relationships

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2D COrrelation SpectroscopY

• The basis for this experiment
• In the upper figure we see the array of data with
  two successive FTs
• In the lower diagram we see a cartoon of the
  result
• Diagonal peaks are created as full relaxation by
  the originally excited protons is not complete by
  t1, so they are reobserved following the second
  pulse
• Off diagonal peaks give the relationship between
  neighboring spin systems.
• We see that E-C are a coupled spin system which
  is isolated from the A-B-D coupled spin system (A
  is coupled to B and B is coupled to D)
• This molecule would be A-B-D-(group or quaternary
  carbon)-C-E

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Sample Problem 1

• Lets return to our sample 2D-COSY

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Sample Problem 1

• Start wherever you like the ends of the
  resonance set is typically a good place to start
  as coupling will only be to one side
• For this example lets look at the triplet at d
  0.9
• This is coupled to two of the three sets of
  protons from d 1.5 to 2.0
• The integration of the triplet is three and each
  multiplet integrates to 1, so we come to the
  first problem the CH3 is bound to a carbon
  that bears two anisotropic protons!
• We now have the fragment CH3-CHaHb-

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Sample Problem 1

• Now follow the trail what is the signal that
  these two multiplets are coupled to?
• We quickly see they are both coupled to the most
  downfield multiplet on the 1H NMR
• This multiplet integrates to one, so we now have
  the fragment CH3-CHaHb-CH-EWG
• Continuing, we see this multiplet is coupled to
  the multiplet at d 2.3 which integrates to one

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Sample Problem 1

• This multiplet is coupled to two others, each
  integrating to one hydrogen
• Keep in mind we may be in a ring system where the
  Jtrans ? Jcis
• We can finish the trail to the remaining
  signals
• We are at a point of confusion as we have the
  following fragment deduced CH3-CHaHb-CH(EWG)-CH-
  CH-CH-CH-CH
• Too many carbons, but we need to know which
  carbon is deficient by one hydrogen to make our
  ring

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HSQC - Heteronuclear Single-Quantum Correlation

• DESCRIPTION The 2D HSQC (Heteronuclear
  Single-Quantum Correlation) experiment permits to
  obtain a 2D heteronuclear chemical shift
  correlation map between directly-bonded 1H and
  X-heteronuclei (commonly, 13C and 15N) .
• It is widely used because it is based on
  proton-detection, offering high sensitivity when
  compared with the conventional carbon-detected 2D
  HETCOR experiment. Similar results are obtained
  using the 2D HMQC experiment.

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Sample Problem 1

• The HSQC is easy to interperet assigned all Hs
  for each CThe 1H NMR is on the F1 dimension and
  an actual 13C NMR is used on the F2 for reference
• In this experiment a 13C acquisition is never
  done!
• Simply match 1H multiplets with their respective
  carbons
• Here you can determine if two Hs are connected to
  the same carbon
• Coupling this with DEPT you can confirm you have
  assigned all protons to a carbon

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Sample Problem 1

• A little larger, with the uninteresting region of
  the 13C spectrum deleted

We see that these 3 sets of Hs are bound to the
same carbon
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Sample Problem 1

• If we put this together with the COSY data
• CH3-CHaHb-CH(EWG)-CH-CH-CH-CH- becomes
• CH3-CH2-CH(EWG ester)-CH2-CH2-(EWG)
• From a reference text we find that the protons on
  a carbon bound to the oxygen end of the ester
  will show up downfield (d 4.5) of the protons on
  a carbon bound to the carbonyl carbon of the
  ester (d 2.3)
• We can now construct the compound

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HMBC Heteronuclear Multiple Bond Correlation

• DESCRIPTION The 2D HMBC experiment permits to
  obtain a 2D heteronuclear Chemical Shift
  correlation map between long-range coupled 1H and
  heteronuclei (commonly, 13C).
• It is widely used because it is based on
  proton-detection, offering high sensitivity when
  compared with the carbon-detected.
• In addition, long-range proton-carbon coupling
  constants can be measured from the resulting
  spectra.   

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HMBC Heteronuclear Multiple Bond Correlation

• The power of this technique is it allows us to
  see through a quarternary carbon center!
• The drawback is that for small molecules with
  tight ring or fused-ring systems (like many of
  the unknowns) everything may be correlated to
  everything else!
• Knowing the structure of our sample problem,
  lets look at the HMBC   

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HMBC Heteronuclear Multiple Bond Correlation
From this spectrum, we see the set of resonances
that are connected from the terminal CH3- group
towards the oxygen end of the ester (red) We see
the set of resonances that start from the
carbonyl end of the ester (blue) We see the two
ends that are associated with the ester carbonyl
carbon! (green)
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Sample Problem 2 - IR
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Sample Problem 2
M 154.0 23.9 M1 155.0 2.7
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Sample Problem 2
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Sample Problem 2
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Sample Problem 2
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Sample Problem 2
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Sample Problem 2
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Sample Problem 2
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Sample Problem 2
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Sample Problem 3
M 156.0 8.4 M1 157.0 0.9
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Sample Problem 3
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Sample Problem 3
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Sample Problem 3
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Sample Problem 3
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Sample Problem 3
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Sample Problem 3
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Sample Problem 3