Use through bond or through space interactions to assign structure 2D Spectroscopy Use through bond or through space interactions to assign structure COSY 1H 1H Correlation Spectroscopy NOESY 1H 1H Nuclear Overhauser Enhancement Spectroscopy HMQC 1H 13C Heteronuclear Multiple (or HETCOR) Quantum Correlation HMBC 1H 13C Heteronuclear Multiple (or long range HMQC) Bond Correlation through SPACE; the rest are through bond

2-DIMENSIONAL SPECTRA: COSY COSY-SQUARES

p. 195 COSY-CROSSHAIRS

p. 196 Example 1 shielding

p. 196

p. 196 10

Example 2 p. 197 4

p. 198 ? 13C NMR

HMQC (Heteronuclear Multiple Quantum Correlation) experiments 1) Short range 13C—H (J ~ 135 Hz or more) 2) Long range 13C—C—C—H (J ~ 10 Hz) you can set J to be whatever you want, to pick up say 2 bond couplings, but experiments are time consuming so we normally do the two above and that will solve most compounds. HMBC is closely related to long range HMQC but gives the same information and is more tolerant of variation in the long range J value

p. 200 1H 13C HMQC 13C-H 3

p. 200 1H 13C 13C-H 1

p. 200 1H 13C 13C-H 1

p. 200 1H 13C 13C-H (J=135) ? 1

p. 200 D B C A J=10Hz 6 2 4 5 3 13C-C-C-H Missing to its own C in this case 1 D 6 1 5 2 4 C 3 A B

Long range HMQC (J = ~ 10Hz) OR HMBC H—C—C—C 1

NOESY experiments pick up CLOSE PHYSICAL CONTACT of non-coupled H’s (through space rather than through bond)

When to expect NOESY Correlations (p. 208 of manual)

BUT NOTE: NOESY spectra ALSO show COSY peaks, Example 3, p. 201 COSY NOESY BUT NOTE: NOESY spectra ALSO show COSY peaks, but in a different colour (here identified in green) 3

Example 4, p. 202 NOESY of penicillin = COSY

Example 5, p. 203 If we can assign HA COSY assigns others 5

If unable to assign HA NOESY COSY peaks p. 203 can assign this but need to run COSY first, to find new peaks COSY peaks run COSY first

Example 6, p. 204 EWG so shifts o-protons downfield 3

what multiplicities – unless the CH3 is there EWG Two places for –NO2 s d d what multiplicities – unless the CH3 is there our compound has one d most downfield (bottom p. 204)

p. 204 d + --CH3 NOESY NOESY Go to NOESY spectrum, 5

Yes, we see ONE NOESY between a CH3 and one H 1 p. 204 Yes, we see ONE NOESY between a CH3 and one H 1

p. 204 Must be one of these NOESY NOESY 5

multiplicity p. 205 d d t t d d d t t d d d 4d + 2t 4d + 2t 3

Now think about couplings to these d d t t d d d t t d d d Now think about couplings to these d t t d } we should be able to see these in the COSY d t d

This was the H with NOESY, we now look in COSY 1 p. 205 This was the H with NOESY, we now look in COSY 1

COSY of the aromatic region p. 205 NOESY d-t -t -d d-d 7

Example 7, p. 206 from 2009 Final: Which isomer is correct?

NOESY Spectrum (COSY peaks suppressed), p. 207 Resonances at 9 and 10 ppm do NOT show any short range HMQC (i.e. they are the OH!)

Left with 1,2 or 5 as possible answers: go to COSY: NOESY shows that OH has near H and there is another pair of H’s across ring fusion point that are close: Rules out 3,4,7,8,9,10 and the fact that the one near the OH is a doublet rules out 6 Left with 1,2 or 5 as possible answers: go to COSY: Note: there are 2 singlets! Can only be 2 COSY of aromatic region

ASSIGNMENT 8