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Multidimensional NMR Experiments
Chem 8361/4361:Interpretation of Organic Spectra
20092013 Andrew Harned & Regents of the University of Minnesota
2D NMR SpectroscopyGeneral Information
More complicated experiments to set up than 1H and 13C Changes in pulses (#, length, angles, mixing times, etc.) Observe effects based on relationship of nuclei
**Can be homonuclear (same nuclei) (e.g. HH) or heteronuclear (different nuclei) (e.g. HC, HP, etc.)**
Will only go over the what the experiments tell you and how to interpret, and only for the most common and widely used for solving organic structures
DEPT, HH COSY, HMQC (HETCOR), HMBC, INADEQUATE (CC COSY)
There is a whole alphabet soup of other experiments (both 1D and 2D)
EXSY, TOCSY, HOHAHA, INEPT, WATERGATE, and many morehttp://www.chem.ox.ac.uk/spectroscopy/nmr/acropage.htm
2D NMR SpectroscopyNumber of Protons on Carbon
DEPT (Distortionless Enhancement by Polarisation Transfer
Used to be known as APT (Attached Proton Test) DEPT is 1H-detected; APT is 13C-detected
Tells you how many protons are attached to a particular carbon negative peaks = CH2 positive peaks = CH and CH3 (distinguishable with further processing) missing peaks = carbons w/o protons
With a little help from IR and chemical shift of 1H and 13C, can get a rough idea of molecular weight
2D NMR SpectroscopyNumber of Protons on Carbon
DEPT (Distortionless Enhancement by Polarisation Transfer
1
1 = Carbon spectrum
2
2 = CH2 CH, CH3
3
3 = CH
135pulse
90pulse
Tells you which protons are coupled to one another Very useful when peaks are overlapping in 1H NMR and you are unable to calculate coupling constants, or when there are a lot of similar coupling constants Cross peaks are coupled to each other
Newer method is DQF (Double Quantum Filtered)-COSY same information, but looks cleaner
2D NMR SpectroscopyWho is Talking to Who?
1H1H COSY (Correlation Spectroscopy)
C C C
H
1 bond HH coupling
H
2D NMR SpectroscopyWho is Talking to Who?
1H1H COSY (Correlation Spectroscopy)
1H1H
4H2H 2H 1H
3H3H
2H
Overlapping protons and a lot of similar coupling constants
Raffinosea trisaccharide
2D NMR SpectroscopyWho is Talking to Who?
1H1H COSY (Correlation Spectroscopy)
Raffinosea trisaccharide
2D NMR SpectroscopyWho is Talking to Who?
1H1H COSY (Correlation Spectroscopy)
4H
1H
1H2H2H1H
3H3H
2H
2D NMR SpectroscopyWho is Talking to Who?
1H1H COSY (Correlation Spectroscopy) DQF-COSY: Double Quantum Filtered COSY cleans up the spectrum by reducing noncoupled systems (e.g. CH3 singlets)
CH2
CH2
H3C CH3
HO
Ipsenol
2D NMR SpectroscopyWho is Talking to Who?
1H1H COSY (Correlation Spectroscopy) DQF-COSY: Double Quantum Filtered COSY cleans up the spectrum by reducing noncoupled systems (e.g. CH3 singlets)
CH2
CH2
H3C CH3
HO
Ipsenol
2D NMR SpectroscopyWho is Talking to Who?
1H1H COSY (Correlation Spectroscopy)
C6H10O2
2D NMR SpectroscopyWho is Talking to Who?
1H1H COSY (Correlation Spectroscopy)
O
O
Tells you which protons are coupled to one another Very useful when peaks are overlapping in 1H NMR and you are unable to calculate coupling constants, or when there are a lot of similar coupling constants Cross peaks are coupled to each other
Recall...1H1H COSY
C C C
H
H
2 & 3 bond HH coupling
H
Tells you which protons are coupled to one another Very useful when peaks are overlapping in 1H NMR and you are unable to calculate coupling constants, or when there are a lot of similar coupling constants Cross peaks are coupled to each other
Recall...1H1H COSY
C C C
H
H
2 & 3 bond HH coupling
H
4H
1H
1H2H2H1H
3H3H
2H
This can still causeambiguities!
2D NMR SpectroscopyWho is Talking to Who?
1H1H TOCSY (Total Correlation Spectroscopy) Tells you which protons are in the same spin system (a continuous chain of spin-spin coupled protons) Magnetization from HA is transferred to HB, which then transfers to HC and on down the line
Can be run as either a 1D or 2D experiment Running as a 1D experiment greatly simplifies spectra with severe signal overlap Related experiment (HOHAHA) gives essentially the same information Can also observe one-bond 1H13C couplings (HMQC-TOCSY, hetero-TOCSY, HEHAHA) - will not discuss
C C C
HA HBC C
HC HD HE
1D TOCSYSpin System Identification
1H1H TOCSY (Total Correlation Spectroscopy) Irradiate at frequency of proton of interest Wait a period of time (typically 20 to 400 ms) and then collect1D spectrum Only observe protons to which magnetization has been transferred Short periods of time (20 ms) will only give rise to single step transfers; longer periods of time allow magnetization to propagate further
- and -lactose
1D TOCSYSpin System Identification
OH4
O
H3
HO
H2
H1OHH5
OH
OHO
HO
H
H
HO
H
HOHH
OH
-lactose4.67 ppm
H6,H6'
1D TOCSY
Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, 2nd Ed., Elsevier, 2009.
OHN
OO
HN
OO
N3
OO
OO
O
OO
O2A B,C D
12
34
56
1D TOCSY
Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, 2nd Ed., Elsevier, 2009.
O
HN
O
O
HN
O
O
N3
O
O
O
O
O
O
O
O
2
A
B,C
D
12
34
56
2D TOCSYSpin System Identification
1H1H TOCSY (Total Correlation Spectroscopy) Cross peaks are in the same spin system
O
OHHO
N3O
O
12
3 4
56
COSY TOCSY
Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, 2nd Ed., Elsevier, 2009.
NN
23
45
6
7
8
9 101112
13
17
19
2925
23
2D TOCSY Cross peaks are in the same spin system
Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, 2nd Ed., Elsevier, 2009.
Intermediate in biomimetic synthesis of manzamine
NN
23
45
6
7
8
9 101112
13
17
19
2925
23
2D TOCSY Cross peaks are in the same spin system
Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, 2nd Ed., Elsevier, 2009.
Intermediate in biomimetic synthesis of manzamine
NN
23
45
6
7
8
9 101112
13
17
19
2925
23
2D TOCSY Cross peaks are in the same spin system
Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, 2nd Ed., Elsevier, 2009.
Intermediate in biomimetic synthesis of manzamine
New DevelopmentsDeconvolution via MDEC
MDEC (Multi Frequency Homonuclear Decoupling) Conceptually the same as the homonuclear decoupling experiment mentioned earlier, but allows multiple frequencies to be decoupledat the same time
J. Am. Chem. Soc. 2009, 131, 1599415995
(a) 1H NMR(b) irr @ H-1(c) irr @ H-1/H-7(d) irr @ H-1/H-3a/H-7
H-2 (dddd)
H-2 (app dt)
H-2 (dd, J = 3.3, 12.2 Hz)
H2
H
Me
H1
OHH3b
H3a MeMe
H7
123
7
OH
X
X
X
New DevelopmentsDeconvolution via MDEC
1D-TOCSY-MDEC
J. Am. Chem. Soc. 2009, 131, 1599415995
123 4
O
OMe
H
H
H
MeMe
H
6
(a) 1H NMR(b) 1D-TOCSY irr @ H-3(c) 1D-TOCSY irr @ H-3 with MDEC @ H-1b, H-2b, H-3
H-2a XX
X
2D NMR SpectroscopyWho is Talking to Who?
1H13C COSY HETCOR (Heteronuclear Correlation)
older experiment; 13C-detected HMQC (Heteronuclear Multiple Quantum Correlation) and HSQC (Heteronuclear Single Quantum Correlation)
newer experiments; 1H-detected; largely replaced HETCOR Both give same information, experimentally very different Peaks have one-bond coupling (i.e. attached directly) Compliments DEPT Particularly useful for diastereotopic protons
C C C
H
1 bond HC coupling
2D NMR SpectroscopyWho is Talking to Who?
HMQC
C C C
H
1 bond HC coupling
2D NMR SpectroscopyWho is Talking to Who?
HMQC
C C C
H
1 bond HC coupling
DiastereotopicProtons
2D NMR SpectroscopyWho is Talking to Who?
HMQC
Can see into multiplets
H2C
O
CH3
H
HH3C
H3C
Caryophyllene Oxide
2D NMR SpectroscopyWho is Talking to Who?
HMQC
O
O
2D NMR SpectroscopyHO
Cl
2D NMR SpectroscopyHO
Cl
2D NMR SpectroscopyHO
Cl
2D NMR SpectroscopyWho is Talking to Who?
1H13C COSY (Long Range)
COLOC (Correlated spectroscopy for Long range Couplings) older experiment; 13C-detected
HMBC (Heteronuclear Multiple Bond Coherence) newer experiment; 1H-detected; completely replaced COLOC
Both give same information, experimentally very different Peaks have two- or three-bond coupling Sees through heteroatoms and quaternary carbons Can be very complicated, but is very powerful
C C C
H
2 and 3 bond HC couplings
H1
2 3C O C
H
H1
2 3C C C
H
HO1
2 3
2D NMR SpectroscopyWho is Talking to Who?
HMQC
C C C
H
1 bond HC coupling
2D NMR SpectroscopyWho is Talking to Who?
HMBC
C C C
H
2 and 3 bond HC couplings
H1
2 3
2D NMR SpectroscopyWho is Talking to Who?
OCH3
OH
OH
OCH3
or
2D NMR SpectroscopyWho is Talking to Who?
OCH3
OH
OH
OCH3or
2D NMR SpectroscopyWho is Talking to Who?
OCH3
OH
OH
OCH3or
2D NMR SpectroscopyWho is Talking to Who?
OCH3
OH
OH
OCH3or
2D NMR SpectroscopyWho is Talking to Who?
OCH3
OH
OH
OCH3or
2D NMR SpectroscopyWho is Talking to Who?
13C13C COSY
INADEQUATE (Incredible Natural Abundance Double Quantum Transfer Experiment) tells what carbons are attached to each other if you know what type of carbon it is (C, C=O, CH, CH2, CH3, etc.) from DEPT, you can almost write down the entire gross structure by running two NMR experiments BUT it is 13C13C coupling
probability of one 13C is 0.01 two next to each other 0.01x0.01 = 0.0001 (~1 molecule in 10,000)
Need lots of sample and instrument time to overcome In our facility: 80% v/v, overnight, 500 MHz = nothing
C C C
1 bond CC coupling
ON
2D NMR SpectroscopyWho is Talking to Who?
INADEQUATE
C C C
1 bond CC coupling
2D NMR SpectroscopyWho is Talking to Who?
INADEQUATE Cross peaks show up as doublets = JCC Diagonal is midway between the two doublets
5 4 1 9 103 11 2 15 126,714
2D NMR Spectroscopy
OH
CH C CH CH2 C CH2
CH3,CH3,CH2,CH3
2D NMR Spectroscopy
2D NMR Spectroscopy
C C,CH
2D NMR Spectroscopy
C CCH CH CH2 CH2 CH3CH3 x2
O
Br
WhichIsomer?
2D NMR Spectroscopy
O
Br
2D NMR Spectroscopy
O
Br