Multidimensional NMR Experiments

Chem 8361/4361: Interpretation of Organic Spectra

2009 Andrew Harned & Regents of the University of Minnesota

2D NMR Spectroscopy
General 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 more
http://www.chem.ox.ac.uk/spectroscopy/nmr/acropage.htm

2D NMR Spectroscopy
Number 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 protons, can get a rough idea of molecular weight

2D NMR Spectroscopy
Number of Protons on Carbon
DEPT (Distortionless Enhancement by Polarisation Transfer
1 = Carbon spectrum 2 = CH2 CH, CH3 3 = CH

90 pulse 135 pulse

2D NMR Spectroscopy
Who is Talking to Who?
1H1H

COSY (Correlation Spectroscopy)

Tells you how 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

H C

H C C

1 bond HH coupling

Newer method is DQF (Double Quantum Filtered)-COSY

same information, but looks cleaner

2D NMR Spectroscopy
Who is Talking to Who?
1H1H

COSY (Correlation Spectroscopy)

Overlapping protons and a lot of similar coupling constants

3H 1H 4H 1H 2H 2H 1H 3H 2H

Exercise 5.10 pp 298

2D NMR Spectroscopy
Who is Talking to Who?
1H1H

COSY (Correlation Spectroscopy)

Exercise 5.10 pp 301

2D NMR Spectroscopy
Who is Talking to Who?
1H1H

COSY (Correlation Spectroscopy)

2H 3H 1H 2H 2H 1H 4H 3H

1H
pp 301

2D NMR Spectroscopy
Who 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

HO H3C

CH2 CH3

Ipsenol

pp 253

2D NMR Spectroscopy
Who 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

HO H3C

CH2 CH3

Ipsenol

pp 253

2D NMR Spectroscopy
Who is Talking to Who?
1H1H

COSY (Correlation Spectroscopy)

C6H10O2

pp 408

2D NMR Spectroscopy
Who is Talking to Who?
1H1H

COSY (Correlation Spectroscopy)

O O

pp 409

2D NMR Spectroscopy
Who is Talking to Who?
1H13C

COSY

HETCOR (Heteronuclear Correlation) older experiment; 13C-detected HMQC (Heteronuclear Multiple Quantum Correlation) newer experiment; 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
H C C C

1 bond HC coupling

2D NMR Spectroscopy
Who is Talking to Who?
HMQC

H C C C

1 bond HC coupling

2D NMR Spectroscopy
Who is Talking to Who?
HMQC

Diastereotopic Protons
H C C C

1 bond HC coupling

2D NMR Spectroscopy
Who is Talking to Who?
HMQC

Can see into multiplets

H3C H H3C H H2C CH3 O

Caryophyllene Oxide

pp 262

2D NMR Spectroscopy
Who is Talking to Who?
HMQC

O O

pp 409

2D NMR Spectroscopy
HO Cl

pp 410

2D NMR Spectroscopy
HO Cl

pp 411

2D NMR Spectroscopy
HO Cl

pp 411

2D NMR Spectroscopy
Who 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
H
1 1

H
1

H O
2 3

O C
2 3

C
2

C
3

2 and 3 bond HC couplings

2D NMR Spectroscopy
Who is Talking to Who?
HMQC

H C C C

1 bond HC coupling

2D NMR Spectroscopy
Who is Talking to Who?
HMBC

H
1

C
2

C
3

2 and 3 bond HC couplings

2D NMR Spectroscopy
Who is Talking to Who?

OH OCH3

or

OCH3 OH

pp 441

2D NMR Spectroscopy
Who is Talking to Who?
OH OCH3

or
OH

OCH3

pp 442

2D NMR Spectroscopy
Who is Talking to Who?
OH OCH3

or
OH

OCH3

pp 442

2D NMR Spectroscopy
Who is Talking to Who?
OH OCH3

or
OH

OCH3

pp 443

2D NMR Spectroscopy
Who is Talking to Who?
OH OCH3

or
OH

OCH3

pp 443

2D NMR Spectroscopy
Who 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

O N C C C

1 bond CC coupling

2D NMR Spectroscopy
Who is Talking to Who?
INADEQUATE

1 bond CC coupling

pp 266

2D NMR Spectroscopy
Who is Talking to Who?
INADEQUATE
Cross peaks show up as doublets = JCC Diagonal is midway between the two doublets
5 4 1 9 10 3 11 6,7 2 14 15 12

pp 266

2D NMR Spectroscopy
CH C CH CH2 C CH2 CH3,CH3,CH2,CH3

OH

pp 297 DEPT on pp 294

2D NMR Spectroscopy

pp 434

2D NMR Spectroscopy

C,CH

pp 436

2D NMR Spectroscopy
C CH CH C CH2 CH2 CH3 x2 CH3

Which Isomer?
Br

pp 436

2D NMR Spectroscopy

Br

pp 435

2D NMR Spectroscopy

Br

pp 435