The  previous  slide  may  be  found  at    h5p://www.jkwchui.com/2011/12/interpre@ng-­‐proton-­‐nmr-­‐overview/  

CH203  Lecture  16  October  10,  2014    Complex  coupling  13C  NMR  

1960:  Bruker  KIS-­‐1  NMR  (25  MHz)  

How  much  informa@on  have  we  go5en  out  of  the  NMR  so  far?  

1.  The  loca@on  of  the  hydrogen  resonance  in  ppm  (chemical  shiY).  Tells  us  the  local  electronic  environment  of  the  hydrogen.    

2.  The  number  of  different  hydrogen  resonances.  Tells  us  how  many  sets  of  nonequivalent  hydrogens  are  present.  

3.  The  number  of  hydrogens  in  each  nonequivalent  set  by  integra@on.  

4.  The  number  of  neighboring  hydrogens.  5.  The  orienta@on  of  the  neighboring  hydrogens  

(coupling  constant).    

Spin-­‐spin  coupling  in  a  vicinal  two  hydrogen  system  

Vocabulary  

C C

HH

C C

H H

C C

H

H

C C

H

H

H

H

C C

H

C H

H

H

H

H

H

H

3J,  vicinal  6-­‐8  Hz  

3J,  vinylic  cis  5-­‐10  Hz  

3J,  vinylic  trans  11-­‐18  Hz  

2J,  vinylic  geminal  0-­‐5  Hz  

2J,  geminal  0-­‐5  Hz  

4J,  allylic  0-­‐1  Hz  

2J,  ortho  7-­‐9  Hz  

3J,  meta  2-­‐3  Hz  

4J,  para  0-­‐1  Hz  

Repor@ng  NMR  data  

10  

The  ethyl  group  

11  

The  isopropyl  group  

Complex  coupling  

The  Hb  signal  is  split  by  Ha  (Jab)  and  then  by  Hc  (Jbc)  to  give  a  doublet  of  doublets.  (This  only  applies  if  Jab  and  Jbc  are  not  equal  or  close  to  equal.)  

Complex  coupling  

The  Hb  signal  is  split  by  Ha  (Jab)  and  then  by  two  Hc  (Jbc)  to  give  a  doublet  of  triplets.  (This  only  applies  if  Jab  and  Jbc  are  not  equal  or  close  to  equal.)  

What  happens  when  the  Js  are  equal  or  close  to  equal?    

When  Jab  and  Jbc  are  close  to  the  same  magnitude,  the  spliang  tree  does  not  generate  the  expected  nine  signals  of  a  triplet  of  triplets.  Only  five  peaks  are  seen  due  to  overlap.    

What  happens  when  the  Js  are  equal  or  close  to  equal?    

In  this  case,  Jab  and  Jbc  are  close  to  the  same  magnitude  because  they  are  in  a  flexible  chain.  Rota@on  averages  the  coupling  constants  to  about  the  same  value.    In  general,  where  you  would  expect  to  see    (n  +1)  x  (m  +1)  peaks,  a  flexible  system  like  this  will  give  (n  +  m  +1)  peaks.    (n  +1)  x  (m  +1)  =  9  peaks  expected    (n  +  m  +1)  =  5  peaks  observed  

What  happens  when  the  Js  are  equal  or  close  to  equal?    

In  1-­‐chloro-­‐3-­‐bromopropane,    Jab  and  Jbc  are  almost  equal.  We  do  not  see  the  expected  nine  peaks  [(n  +1)  x  (m  +  1)]  of  a  triplet  of  triplets  for  Hc.  Only  five  peaks  (n  +  m  +1)  are  observed.        

What  happens  when  the  Js  are  equal  or  close  to  equal?    

In  1-­‐chloropropane,    Jab  and  Jbc  are  almost  equal.  We  do  not  see  the  expected  twelve  peaks  [(n  +1)  x  (m  +  1)]  of  a  triplet  of  quartets  for  Hb.  Only  six  peaks  (n  +  m  +1)  are  observed.        

Geminal  coupling  in  an  alkene  

NMR  of  ethyl  propenoate.  The  region  around  6  ppm  needs  to  be  expanded  to  see  the  spliang  pa5erns  and  measure  the  coupling  constants.  

Geminal  coupling  in  an  alkene  

NMR  of  ethyl  propenoate.  The  signals  for  the  three  vinylic  hydrogens  are  each  a  doublet  of  doublets.  The  pa5ern  changes  as  the  coupling  constant  changes.  

Geminal  coupling  in  a  ring  

2-­‐methyl-­‐2-­‐vinyloxirane.  The  two  H  atoms  on  the  oxirane  ring  are  nonequivalent,  so  they  exhibit  geminal  coupling.  

Topicity  

Hydrogens  are  homotopic  if  replacement  does  not  generate  a  new  chiral  center.  D  (2H)  is  some@mes  used  as  the  test  replacement.    In  dibromomethane,  the  hydrogens  are  homotopic  and  so  are  always  iden@cal.  

BrC

Hb

BrHa

BrC

D

BrHa

BrC

Hb

BrD

Topicity  

Hydrogens  are  enan@otopic  if  replacement  does  generate  a  new  chiral  center.    In  bromofluoromethane,  the  hydrogens  are  enan@otopic  and  so  are  iden@cal  in  achiral  environments.  

BrC

Hb

FHa

BrC

D

FHa

BrC

Hb

FD

Topicity  

Groups  are  diastereotopic  if  replacement  does  generate  a  new  chiral  center  in  a  molecule  with  at  least  one  exis@ng  chiral  center.    In  3-­‐methyl-­‐2-­‐butanol,  the  two  methyl  groups  bonded  to  C3  are  diastereotopic  and  so  are  not  equivalent.  Diastereotopic  groups  will  exhibit  different  chemical  shiYs.  

C

OH

CH3H3C

H3C

C C

OH

CH3H3C

D3C

C C

OH

CH3D3C

H3C

Topicity  

O

CH3H3C

H3C

The  two  methyl  groups  at  C3  in  3-­‐methyl-­‐2-­‐butanone  are  not  diastereotopic  and  appear    as  a  clean  doublet  at  about  1  ppm.  

Topicity  

The  two  methyl  groups  at  C3  in  3-­‐methyl-­‐2-­‐butanol  are  diastereotopic  and  appear    as  two  doublets  at  about  1  ppm.  

OH

CH3H3C

H3C

Topicity  

Homotopic:    replacement  does  not  generate  a  new  chiral  center          always  iden@cal          same  chemical  shiYs  

 Enan@otopic:    replacement  does  generate  a  new  chiral  center    

       iden@cal  in  achiral  environments          same  chemical  shiYs  in  achiral  NMR  experiment  

 Diastereotopic:  replacement  does  generate  a  new  chiral  center  in  a  molecule  

         with  at  least  one  exis@ng  chiral  center          different  chemical  shiYs  

 

What  is  an  achiral  NMR  experiment?  

Ways  to  make  an  achiral  NMR  environment    Chiral  solvent:  not  many  available,  very  expensive    Chiral  addi@ve:  “shiY  reagents”  are  chiral  molecules  which  complex  with  the  target  molecule  and  shiY  the  proton  signals  in  one  enan@omer      Chiral  deriva@ves:  chemically  add  a  chiral  group  to  the  mixture  of  enan@omers  to  generate  a  mixture  of  diastereomers  which  will  have  different  NMRs  

What  is  an  achiral  NMR  experiment?  

Sodium  [(R)-­‐1,2-­‐Diaminopropane-­‐N,N,N',N'-­‐tetraacetato]samarate(III),  hydrate    

13C  NMR  and  the  Fourier  Transform  

 There  are  two  kinds  of  NMR  spectrometers:  con@nuous  wave  spectrometers  and  pulse  spectrometers.    

 In  a  CW  spectrometer,  the  sample  is  placed  in  a  sta@c  magne@c  field  and  swept  with  radiofrequency  (Rf)  energy.  The  CW  NMR  spectrum  shows  peaks  at  frequencies  where  there  is  absorp@on  of    Rf  energy.    

 In  a  pulsed  spectrometer,  the  sample  is  placed  in  a  sta@c  magne@c  field  and  then  hit  with  a  pulse  of  RF  waves  powerful  and  wide  enough  to  simultaneously  excite  all  nuclei  in  the  sample.  AYer  the  pulse  the  nuclei  return  to  their  ground  states  by  radia@ng  the  absorbed  energy.  The  pulsed  spectrometer  detects  this  reradiated  energy  as  a  Free  Induc@on  Decay  (FID)  signal.  The  computer  uses  the  Fourier  Transform  (FT)  to  convert  the  FID  @me  data  into  frequency  data  which  is  presented  like  the  original  CW  spectra.  

13C  NMR  

Problems  with  obtaining  13C  NMR  spectra    13C  makes  up  only  1%  of  the  carbon  in  a  sample.  The  gyromagne@c  ra@o  of  13C  is  one-­‐fourth  of  that  of  1H.    This  means  that  the  1H  signal  is  1000  @mes  stronger  than  the  13C  signal.    To  get  a  useable  spectrum,  the  FT-­‐NMR  pulses  the  sample  mul@ple  @mes  and  the  computer  sums  the  FIDs  to  enhance  peaks  and  minimize  noise.        

13C  NMR  

The  13C  resonance  signal  is  also  split  by  the  protons  a5ached  to  it.  In  the  top  spectrum  of  norbornane,  carbons  2,3,4,  and  6,  which  are  all  equivalent  and  all  have  two  hydrogens  bound,  appear  as  a  triplet.    A  pulse  spectrometer  is  able  to  irradiate  the  sample  with  a  second  radiofrequency  energy  which  is  absorbed  by  all  the  hydrogens  and  decouples  their  spin  states  from  the  carbon  spin  states.  The  spin  decoupled  spectrum  is  on  the  bo5om.  Each  set  of  equivalent  carbons  is  seen  as  one  peak.  

13C  chemical  shiYs  

13C  chemical  shiYs  compared  to  1H  

=>

Pulse  sequences  

DEPT

Goto

66 Bruker AVANCE User’s Guide

Figure 18: DEPT Pulse Sequence

Acquisition and Processing 6.3

Insert the sample in the magnet. Lock the spectrometer. Readjust the Z and Z2 shimsuntil the lock level is optimized. Tune and match the probehead for 13C observation,1H decoupling.

Reference spectraSince DEPT is a 13C-observe, 1H-decouple experiment, the first step would be toobtain a reference 1H spectrum of the sample to determine the correct o2 for 1Hdecoupling. The second step would then be to obtain a 1H-decoupled 13C spectrumto determine the correct o1 and sw for the DEPT experiments. However, both ofthese steps were already carried out in Section 4.3 starting on page 37. So, a 1H-decoupled 13C reference spectrum of this sample can be found in carbon/3/1. (Theone thing to be aware of is that broadband decoupling was used in carbon/3/1, buthere the cpd sequence WALTZ-16 will be used).

Create a new file directory for the data setEnter re carbon 3 1 to call up the reference spectrum. Enter edc and change thefollowing parameters:

NAME deptEXPNO 1PROCNO 1 .

Click SAVE to create the data set dept/1/1.

Set up the acquisition parametersEnter eda and set the acquisition parameters as shown in Table 22. Use the valuesdetermined in Chapter 5 ‘Pulse Calibration’ for the parameters pl1 and p1 (13Cobserve high power level and 90° pulse time), pl2 and p3 (1H decouple high powerlevel and 90° pulse time), and pl12 and pcpd2 (1H decouple low power level and

cpd

acq

!

! "

!2

!2

13C

1H12JXH

12JXH

12JXH

trd

p1 p2

p3 p4 p0

d2d1 d2d2

Simple  pulse  sequence  

Pulse  sequence  for  a  DEPT  (Distor@onless  Enhancement  by  Polariza@on  Transfer)  experiment.  

Pulse  sequences  -­‐  DEPT  

Pulse  sequences  -­‐  APT  

What  is  it?  

C6H8O4  

1H  13C  

(13C  signals  are  not  propor@onal  to  the  number  of  carbons  at  that  ppm.)    

2H  

6H  

What  is  it?  

C6H8O4  

1H  13C  

(13C  signals  are  not  propor@onal  to  the  number  of  carbons  at  that  ppm.)    

2H  

6H  

H

H

O

O

OCH3

OCH3Dimethyl  maleate  

What  is  it?  

C4H4S  (13C  signals  are  not  propor@onal  to  the  number  of  carbons  at  that  ppm.)    

1H  

2H   2H   13C  

What  is  it?  

C4H4S   (13C  signals  are  not  propor@onal  to  the  number  of  carbons  at  that  ppm.)    

1H  

2H   2H   13C  

S

Thiophene