Chapter 4.

Nuclear magnetic resonance spectroscopy

I. 1H NMR

Reading: Pavia the rest of Chapter 3 Chapter 5 Chapter 6.1

1. Chemical equivalence
- protons in chemically identical environments - are chemically equivalent - exhibit the same - equivalence through symmetry considerations
CH3 H3C CH3 CH3

O H3C CH3

1 signal for 12 1H

1 signal for 6 1H

- obvious non-equivalence
CH3 H H
O O O O

O H3C O CH3

H CH3

2 sets: 1 signal for 6 1H in CH3 1 signal for 4 1H in CH

2 sets: 1 signal for 6 1H in OCH3 1 signal for 4 1H in CH2

2 sets: 1 signal for 3 1H in CH3 1 signal for 3 1H in OCH3

Example
Chemical and magnetic equivalence: Proton signal is a singlet

1. Chemical equivalence continued

- spectral regions - chemical environment of the 1H is important: - hybridization effects - electronegativity effects - magnetic anisotropy effects
often given as inset

variable

Fig. 3.49

see p. A-8 ff

deshielded

shielded

2. Integration
- determines the number of equivalent 1H for a signal - determined through the area under the signal - given through a step trace (need a ruler!) - provides first important label
55.5 : 22 : 32.5 2.5 : 1 : 1.5 5: 2 :3 for a total of 10 1H!

or mm 5H 2H 3H

5H digital information:

2H

3H

3. Simple (singlet) spectra

- signal is only one peak: singlet, s
:2.0 ppm
O H3C CH3

-scale: 10 -

s (second important label)

reported: 2.1 s (6H) C3H6O

4.0

3.0

2.0

1.0

0 ppm: -scale

O H3C O CH3

s 3H -OCH3

s : multiplicity 3H : integration -CH3 : assignment (third important label)

work this way

reported: 2.0 s (3H) 3.65 s (3H) C3H6O2

4.0

3.0

2.0

1.0

0 ppm

3. Simple spectra continued

C6H10O4

s 3H -OCH3

s 2H -CH2-

integration: 1.5 : 1 or 3 : 2 or revised 6:4

reported: 2.55 s 4H 3.65 s 6H for a total of 10 1H

4.0

3.0

2.0

1.0

0 ppm

C6H8O4
s 1H C=C-H

s 3H -OCH3

thoughts: - aromatic? - U? - empirical formula? reported: 3.8 s 6H 6.85 s 2H for a total of 8 1H

7.0

4.0

3.0

2.0

1.0

0 ppm

4. Estimation of 1H
- from increment systems - for X-CH2-Y (and X-CH3, where Y adds 0)
1H (ppm) = 0.23 + increments for X and Y substituents
O

see p. A-17

1Ha = 0.23 + 1.55 + 0 = 1.78 ppm (exp. 2.0 ppm) ok 1Hb = 0.23 + 3.13 + 0 = 3.36 ppm (exp. 3.65 ppm) ok 1Ha = 0.23 + 1.55 + 0.47?= 2.25 ppm (exp. 2.55 ppm) ok
b

O O

a
O

1Hb = 0.23 + 3.13 + 0 = 3.36 ppm (exp. 3.65 ppm) ok

- for

trans gem cis

H

1H (ppm) = 5.25 + increments for gem, trans and cis substituents

a
O O O

see p. A-18

1Ha = 0.23 + 3.13?+ 0 = 3.36 ppm (exp. 3.8 ppm) ok? 1Hb = 5.25 + 0.84 + 1.15 + 0 = 7.24 ppm (exp. 6.85 ppm) ok
gem cis

4. Estimation of 1H continued
- from an increment system - for
H

1H
Cl

(ppm) = 7.27 + increments for substituents

O

see p. A-19

OH

1Ha = 0.23 + 1.55?+ 3.23?= 5.01 ppm (exp. 4.6 ppm) ok 1Hb = 7.27 + 20.03 + (-0.09) + (-0.09) = 7.15 ppm (exp. 7.5 ppm) ok?
o-Cl p-Cl m-OR

Cl

Cl

1Hc = 11-12 ppm

Cl O

O OH

Cl

Cl

inset; problem: no scale!

7.0 4.0

5. Magnetic anisotropy
- phenomenon observed for protons near -systems - mobile -electrons create local magnetic fields - shielding and deshielding regions - unusual chemical shifts reasoning: general shielding observations:
parallel: deshielded (-) stronger apparent B0 antiparallel: shielded (+) weaker apparent B0

>7 ppm

5-7 ppm

9 ppm

2-3 ppm

-0.5 ppm -1.8 ppm

18

-1.4 ppm

10

6. Spin-spin coupling
- chemically equivalent protons do not always just give a singlet - signal can be split into: - 2 lines: doublet, d - 3 lines: triplet, t # of lines depends on the number of neighbouring 1H: - 4 lines, quartet, q n+1 rule: - 5 lines, quintet, quint n+1 lines in the signal for n equivalent neighbouring 1H - 6 lines, sextet, sext - 7 lines, septet, sept - protons can couple over - 2 bonds: 2J coupling - 3 bonds: 3J coupling
H C C

H C H
H

- 4 bonds or more: 4J, 5J coupling or long-range coupling (mostly not observed)

X

but across multiple bonds:

H H

H H H Y

6. Spin-spin coupling continued

- 3J coupling explained:
H C C

signal observed for this 1H

1H

sees one 1H on the next carbon atom: - total of 2 different spin situations: and - signal for 1H splits into 2 lines: doublet

equal probability same area/height intensity ratio in signal 1:1

total spin observed by 1H: + -

H C H C H

signal observed for this 1H

sees two 1H on the next carbon atom: - total of 3 different spin situations - signal for 1H splits into 3 lines: triplet
1H

total spin observed by 1H: +1 0 -1

intensity ratio in signal 1:2:1

6. Spin-spin coupling continued

- for I = , intensities of the lines within a signal follow the binomial distribution - Pascals triangle 1 1 1 1 1 1 1 6 5 15 4 10 20 3 6 10 15 2 3 4 5 6 1 1 1 1 1 1 septet, outer lines often tough to detect

OH

dont miss the outer lines! looks like only 5 lines

now we can predict 1H spectra

Example
Predict (draw) the NMR spectrum for Consider , multiplicity and integration.
1H
O O

7. Spectra with simple multiplets

s 3H EW-CH3 q 2H EW-CH2-CH3 t 3H -CH2-CH3

Table 3.8: examples of splitting patterns

s (3 H) EW-CH3 t (3 H) -CH2-CH3

O O

q (2 H) -O-CH2-CH3

7. Spectra with simple multiplets continued

- multiplet issues I. Multiplicity CH3CH2CH2CH2Cl quint sext quint? sext? Or both rather mult? Will discuss later. CH3CH2CH2CH2OCH3

Fig. 3.41

Fig. 3.43

7. Spectra with simple multiplets continued

- multiplet issues II. Skewing in multiplets - first information on which protons are coupled
b a d couples to a 1H of a downfield signal c

more complex coupling coupling

4J

8. Coupling constant, J
- number assigned to the spread of the lines in a multiplet - more reliable information on which protons are coupled than skewing - for two multiplets from coupling protons, J is the same
Cl Ph C I C Ph

HA HX

HA J

HX

4 ppm

J, same!

if this spectrum was taken at 60 MHz:

1 ppm or 60 Hz 0.1 ppm 3J 6 Hz

AX spin system: - Pople notation - two chemically different protons, is (relatively) large

8. Coupling constant, J, continued

ICH2CH3

Table 3.9: generalized J values and A-13 ff

all spacings are the same, 3J 7.5 Hz A2X3 spin system: - Pople notation - two sets of chemically different protons, is (relatively) large

Example
Assuming that 3J is greater upon Br-substitution, which structure is correct?
O O2N O Br

O Br O NO2

2 ppm

8. Coupling constant, J, continued

- origin of the coupling: via the electrons in the bonds : interaction between spins of nuclei and electrons size of J depends on the geometry: - 2J depends on the HCH bond angle: larger J with smaller angle (better interaction of -orbitals) C
H

H
2J HH

[Hz]

109 2J 12 Hz 118 2J 5 Hz

Fig. 5.4

H H

- 3J depends on the HCCH torsion angle: minimum function at 90 (no interaction of -orbitals) H C
H

3J

HH

[Hz]

Karplus curve

180 3J 12 Hz 60 4 Hz

Fig. 5.7

HH

3J

9. First and second order spectra

- sets of protons in Table 3.8 are chemically and magnetically equivalent give one Contrast: Example for protons that are chemically, but not magnetically equivalent
Br HA HX HX not A2X2 but AAXX system HX and HX: chemically equivalent

show no J

HA

Br

but HA sees HX trans sees HX cis : magnetically inequivalent two different 3J

gives rise to a second-order spectrum: - splitting patterns, intensities and # of lines are wrong - n+1 rule breaks down

9. First and second order spectra continued

- Second-order spectra are also found for sets of nuclei if /J < 10
Y Z

both in Hz A2X2

300 MHz

A2B2

60 MHz

10. Non-equivalence within a group

- coupling within a group (CH2, e.g.) when protons are not chemically equivalent
HB HA O HC Ph

all three 1H are different (chemically and magnetically) all will couple amongst each other this is not
O H2C H Ph

, HC does not couple into a triplet!

- observed coupling here: 3JAC 3JBC, 2JAB - we expect - three different coupling constants - signals of different multiplicity than so far - we can analyse coupling constants - appearance of a signal through tree-diagrams

10. Non-equivalence within a group continued

- analysis with a tree-diagram simple system: coupling to one type of 1H
H
X

H C

doublet for HA
HA undisturbed signal signal split by HX

HX C HX C

HA

triplet for HA
HA

advanced system: coupling to two types of 1H

H
M

H C

AMX system one doublet for HA with HM, one doublet for HA with HX doublet of doublets for HA, dd
doublet with HX doublet with HM HA
3J 3J

C HX

AX AM

1 signal, 4 lines

10. Non-equivalence within a group continued

- two uses of a tree-diagram towards a spectrum: what does the signal look like? - use larger J first
HA HA

not like this:

- stay symmetrical

: not like this, either!

from a spectrum: what are the coupling constants? - take distance within and between multiplets
HA between

within

for a dd, measure within: distance of lines 1 and 2 or 3 and 4 between: distance of lines 1 and 3 or 2 and 4

10. Non-equivalence within a group continued

- appearance of the spectrum
HB HA O HC Ph

tree-diagram analysis

in Hz: can use for J directly!

dd 1H dd 1H HC HB HA in ppm: can use for J (300 MHz spectrum)

dd 1H

example: JAC appears twice: - in the signal for HA - in the signal for HC note: 3J AC 3J BC but 2JAB

10. Non-equivalence within a group continued

- two practice patterns
Br CH CH2 C Br H O

spin system:

CH CH2 CH2 C(CH3)3

spin system:

multiplicities: tree-diagram (assume J1 > J2):

multiplicities: tree-diagram:

How do you determine which J is which?

10. Non-equivalence within a group continued

- the appearance of a dt as J changes
HA HA

J1 14 Hz J2 3 Hz

J1 14 Hz J2 6 Hz

HA

HA

J1 8 Hz J2 3 Hz

J1 6 Hz J2 3 Hz

10. Non-equivalence within a group continued

- coupling examples in alkenes
R H R H H R R R' H R H R H R' H R' H H H H

1H

are chemically and magnetically equivalent s, no splitting 2 d, 3J 16 Hz (large) 2 d, 3J 8 Hz 2 d, 2J 0-5 Hz 3 dd

5.25 + 1.35 + 0.44 = 7.04
H H3C COOH H

5.25 + 1.00 - 0.29 = 4.96

Table A6.2

11. Non-equivalence for geminal groups

- two protons in CH2 groups - two CH3 in i-propyl groups can be homotopic, enantiotopic, diastereotopic

: which of the three is important for the appearance of the spectrum - homotopic protons: replacement of either 1H gives identical molecules
H X H X D X H X and H X D X

protons are equivalent, give a singlet

- enantiotopic protons: replacement of either 1H gives enantiomers

H X H Y D X H Y and H X D Y

protons appear to be equivalent, give a singlet only in achiral solvents

11. Non-equivalence for geminal groups continued

- diastereotopic protons: replacement of either 1H gives diastereomers
H X H Y* D X H Y* and H X D Y*

Y* contains a C*

protons are not equivalent, have different , often split with 2J coupling

Example
Cl Cl
Cl Cl HH

dd

dd
2J 3J 3J AB AC BC

11 Hz 8 Hz 5 Hz

not a regular CH2 group, H are diasterotopic

11. Non-equivalence for geminal groups continued

- diastereotopic protons: replacement of either 1H gives diastereomers Example

OH

CH3 H3C

*
OH
(d)

not a regular i-propyl group, CH3 are diasterotopic 2 d, not t!

12. Protons on oxygen

Read by yourself: Chapter 6.1 , so that you can explain why CH3CH2OH has these two different spectra

ordinary sample

ultrapure sample