JS Organic Practical Course

Additional NMR spectra to aid structural determination

Three types of data are supplied :-2D homonuclear corelation spectra (HH COSY)-2D heteronuclear corelation spectra (CH COSY)-1D Nuclear Overhauser spectra (NOE)

Data is supplied for experiments :-2 (Benzoin), 3b (1,4-Diphenyl-1,3- butadiene)-5 (2,6-Dimethyl-3-heptan-5-one)-6a (1-Phenylbutane-1,4-diol)-6b (-Phenyl--butyrolactone)-7 (cis-Caran-trans-4-ol)

Additional NMR analysisconnections through bonds and space

Correlation Spectra (COSY) through bond connectionsHH COSY - connections of proton spins through bondsCH COSY- direct link of carbon to proton(s)Long range CH COSY

Connections through spaceNuclear Overhauser (NOE) experiments

1D : Difference NOE, DPFGSE-NOE2D : NOESY, ROESY

How to read a COSY HH COSY

diagonal is the 1D spectrumoff diagonal signal(s) display the connections of the spinstrue signal must have mirror image across the diagonal

CH COSYsignals are the direct correlation between the C and H

Long range CH COSYoften can correlate several protons to a carbon(or vice versa - whichever is most appropriate )e.g. links carbon signals with NO protons directly attached

2 CH COSY Benzoin

(ppm) 8.0 7.2 6.4 5.6 4.8

(pp

130

120

110

100

90.0

80.0

(ppm) 8.00 7.80 7.60 7.40

(pp

134

132

130

128

126

Expansion of aromartic region

Direct correlation of

hydrogen to carbon resonances1H axis

13C axis

3B CH COSY (E,E)-1,4-Diphenyl-1,3-butadiene

(ppm) 7.40 7.20 7.00 6.80 6.60

(pp

134

132

130

128

126

1

2

3

41'2'

3'

4' 6'5'

Direct correlation ofhydrogen to carbon resonances

3B HH COSY (E,E)-1,4-Diphenyl-1,3-butadiene

(ppm) 7.60 7.40 7.20 7.00 6.80 6.60

(pp

7.60

7.40

7.20

7.00

6.80

6.60

6.40

(ppm) 7.60 7.40 7.20 7.00 6.80 6.60

(pp

7.60

7.40

7.20

7.00

6.80

6.60

6.40

1

2

3

41'2'

3'

4' 6'5'

Diagonal contains the 1D spectrum

Connections between atoms are symmetrical about the diagonal

Generally, the higher the contourthe stronger the connection

5 HH COSY 2,6-Dimethyl-5-hydroxyheptan-3-one

(ppm) 4.0 3.2 2.4 1.6 0.8

(ppm)

3.2

2.4

1.6

(ppm) 2.8 2.4 2.0 1.6 1.2 0.8

(ppm)

2.4

2.0

1.6

1.2

1H

1H

O OH

12

3

4

5

6

7

5 CH COSY 2,6-Dimethyl-5-hydroxyheptan-3-one

(ppm) 3.6 3.2 2.8 2.4 2.0 1.6 1.2

(ppm)

72

64

56

48

40

32

24

16

(ppm) 1.12 1.08 1.04 1.00 0.96 0.92 0.88

(ppm)

18.8

18.4

18.0

17.6

17.2

1H

13C

O OH

12

3

4

5

6

7

Methyl region

5 CH COSY 2,6-Dimethyl-5-hydroxy-heptan-3-one

(ppm) 2.72 2.64 2.56 2.48 2.40

(ppm)

44.8

44.0

43.2

42.4

41.6

40.8

40.0

Expansion of the 2.40-2.75ppm region

CH

-CH2-

Spin-Spin Coupling informationfrom the CH2 (Hz)

2.56ppm2.45ppm

2.54ppm

5 Long Range CH COSY 2,6-Dimethyl-5-hydroxyheptan-3-one

(ppm) 3.6 3.2 2.8 2.4 2.0 1.6 1.2

(ppm)

200

160

120

80

40

Notice CH correlations to :

- a longer range i.e. two or more bonds for a CH correlation

- a carbonyl resonancei.e. a quaternary peak

- a hydroxyl peak

Keto Carbon 216 ppm

6A CH COSY of 1-Phenyl-1,4-butanediol

(ppm) 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00

(ppm)

120

100

80

60

40

(ppm) 7.40 7.36 7.32 7.28 7.24

(ppm)

130.0

128.0

126.0

124.0

122.0

OH

HO1H

13C

1

23

4o,m 1H signalsoverlap

p

6A HH COSY of 1-Phenyl-1,4-butanediol

(ppm) 7.2 6.4 5.6 4.8 4.0 3.2 2.4 1.6

(ppm)

7.2

6.4

5.6

4.8

4.0

3.2

2.4

1.6

OH

HO

1

2

34

6B CH COSY -Phenyl--butyrolactone

(ppm) 8.00 7.00 6.00 5.00 4.00 3.00 2.00

(pp

140

120

100

80

60

40

(ppm) 2.80 2.60 2.40 2.20 2.00 1.80

(pp

36

32

28

24

(ppm) 7.68 7.60 7.52 7.44 7.36 7.28 7.20 7.12

(pp

130

128

126

124

122

OOH

41

3 2

2

64

3

5

7 CH COSY cis-caran-trans-4-ol

(ppm) 3.2 2.8 2.4 2.0 1.6 1.2 0.8

(ppm)

72

64

56

48

40

32

24

16

(ppm) 2.00 1.80 1.60 1.40 1.20 1.00 0.80

(ppm)

36

32

28

24

20

16

HCH3

OH

HH

HCH3CH3

(ppm) 2.0 1.6 1.2 0.8

(ppm)

32

28

24

20

16

Me

Me

Me

7 HH COSY cis-caran-trans-4-ol

(ppm) 3.2 2.8 2.4 2.0 1.6 1.2 0.8

(pp

3.2

2.8

2.4

2.0

1.6

1.2

0.8HCH3

OH

HH

HCH3CH3

7 HH COSY cis-caran-trans-4-ol

(ppm) 3.2 2.8 2.4 2.0 1.6 1.2 0.8

(pp

3.2

2.8

2.4

2.0

1.6

1.2

0.8

(ppm) 3.2 2.8 2.4 2.0 1.6 1.2 0.8

(pp

3.2

2.8

2.4

2.0

1.6

1.2

0.8

HCH3

OH

HH

HCH3CH3

More complex NMR experiments to detemine the configuration of the cis-Caran-trans-ol

Long range CH COSYused to find correlations to proton(s) other than those directly attached to a carbonused to establish links to hydroxy groups and quaternary carbon peaks

Nuclear Overhauser Effect (NOE) This will etablish interactions of the spins through SPACEDifference NOE experiment irradiate a specific proton and observe any changes(a normal spectrum is subtracted from the irradiated spectrum to give the DIFFERENCE spectrum

expect to differentiate between the two methyl peaks on the cyclopropyl ringone should be lying in the same plane as the two cis protons on the ring

7 Long range CH COSY cis-Caran-trans-ol

(ppm) 4.0 3.2 2.4 1.6 0.8

(ppm)

72

64

56

48

40

32

24

16

OH

H

H

HOH

H

HH

H

CH3

H

CH3CH3

12

3

78

5

2'

6

9

4

Solvent DMSO-d6

7 Difference NOE NMR cis-Caran-trans-4-ol

0.81.01.21.41.61.82.02.22.42.62.83.0

0.81.01.21.41.61.82.02.22.42.62.83.0

0.81.01.21.41.61.82.02.22.42.62.83.0(ppm)

Normal Spectrum

Difference Spectrum Methyl at 0.93 ppmirradiated

Methyl at 0.89 ppmirradiated

Positive NOE

No NOE