C8953
NMR structural analysis
seminar
Information about classes + 1D 1H-NMR
Jan Novotny
176003@mail.muni.cz
February 26, 2024
Information about classes
Credit:
▶ active attendance (2 absences tolerated)
▶ midterm test and final project/test
Study materials:
https://is.muni.cz/auth/el/1431/jaro2024/C8953/um
E-tests:
https://is.muni.cz/auth/el/1431/jaro2024/C8953/odp
Energy levels splitting
α
β
B0
E
B0ms=+1/2
α
ms=‐1/2
β
s=1/2
ΔE
Nα>Nβ
Behavior of nuclear spin after irradiation by RF pulse
y
x
z
Mz
B0
B0
Bloc
Precession frequency: ω = ‐γB0
Precession frequency affected by nuclear shielding: ω = ‐(1+σ)B0
Chemical shift: δ = ω ‐ ωref
Definition of th relative scale of the chemical shift: δ = (ω ‐ ωref)/ωref.106
ppm
B0 induces local mag. field
Bloc, which affects against B0
Nuclear shielding
RfpulseB1
Characteristic intervals of chemical shifts values
Increase of chemical shift
Increase of shielding
Higher ω Lower ω
12 10 8 6 4 2 0ppm
H
H
H
H
H
H
R H
O
R O
O
H
R1
R2
H
H
R Cl
HH
R H
R
O
H
R N
O
H
H
Trends in chemical shifts
▶ Electronegativity, inductive and mesomeric effects of
substituents
▶ Hybridisation
▶ Relative position towards the ring, double bond
H I
H H
H Cl
H H
H Br
H H
H OR
H H
Cl Cl
H H
Cl Cl
Cl H
H NO2
H H
3 ppm
5,3 ppm
7,3 ppm
2,1 ppm 2,3 ppm 3,1 ppm 4,5 ppm Substituents with ‐I effect
=N+
R2>‐N+
R3>‐NO2>‐NR2
‐SO2R>‐SO3>‐SOR>‐SR
‐F>‐OR>‐NR2>‐CR3
‐F>‐Cl>‐Br>‐I
=N>=NR>‐NR2
‐C=CH>‐CH=CH2>‐CH2‐CH3
=
=
Substituents with +I effects
‐N‐R>‐O‐>S‐
‐C(CH3)3>‐CH(CH3)2>‐CH2CH3>‐CH3
metals
Mesomeric effect
5,29
5,29
6,11
6,52
3,74
3,93
‐M +M
7,24
6,55
7,08
6,70
8,15
7,55
7,70
MM ‐+
Substituents with ‐M effects
‐F, ‐Cl, ‐Br, ‐I, ‐OH, ‐OR, ‐NH2, ‐NHR, ‐NR2, ‐SH, ‐SR
Substituents with +M effect
‐CH=O, ‐RC=O, ‐C(OH)=O, ‐C(OR)=O, ‐C(NH2)=O, ‐NO2, ‐SO3H, ‐C=N=
Spin-spin interaction, J-coupling
H H H
B0 ‐ Bloc
Bloc
Nucleus H: spin α ‐Bn
spin β +Bn
B0 ‐ Bloc + Bn
B0 ‐ Bloc ‐ Bn
H
R R R R
H
Interaction constant J
ωaωb ωc
=ωa+1/2J =ωa‐1/2J
J=ωb‐ωc
B0
Interaction constant J
– CH2 – CH3
▶ Multiplicity of the nucleus I with the spin 1/2 is given by:
m = n + 1, n = number of interacting nuclei with nucleus I
▶ Intensity of lines in multiplet follows Pascal’s triangle
1
1 1
1 2 1
1 3 3 1
1 4 6 4 1
1 5 10 10 5 1
1D 1
H NMR spectrum
HO – CH2 – CH3
3J1
3J2
3J2
3J2
3J2
3J1
3J1
3J1
3J2
3J2
3J2
3J2
3J2
3J2
3J1
3J1
3J1
3J1
Values of J-constants - trends
R1
R2
H
H
R1
H
H
R2
C13
H
C13
H
C13
H
3JHH = 13 ‐ 18 Hz 5JHH = 7 ‐ 12 Hz
1JCH = 125 Hz 1JCH = 160 Hz 1JCH = 250 Hz
N
N
NH2
O
H
H
H
H
H
2JHH= ‐12,5 Hz
3JHH= 12 Hz
CH3
H
C
13
H
OH O
2JCH= 3.1 Hz
5JHH= 2 ‐ 3 Hz
Values of J-constants - trends
H
H
A
B B H
H
A
B
H
H
A
3JHH = 7,5 Hz 4JHH = 1,5 Hz 5JHH = 0,7 Hz
X= Li H Cl OMe F
2JHH (Hz) 7,1 2,5 ‐1,4 ‐2,0 ‐3,2
1D 1
H NMR spectroscopy
▶ the fastest measuring, the highest sensitivity
▶ complicated interpretation in case of more complex
systems
We are looking for:
▶ position of the signal (ppm)
▶ multiplicity (2J, 3J, 4J)
▶ intensity (integral)
▶ halfwidth
We are considering:
▶ chemical/magnetic equivalence
▶ enantiotopicity/diastereotopicity
▶ averaging of signals (dynamics, chemical exchange)
1D 1
H NMR spectrum of methyl-5-acetylsalicylate
1
2
6
3
5
4
7
O
CH3
8
9 O
O
CH3
10
OH
1D 1
H NMR spectrum of methyl-5-acetylsalicylate
1
2
6
3
5
4
7
O
CH3
8
9 O
O
CH3
10
OH
6
4
3
10
8
Notes:
▶ two singlets in the spectrum - two
isolated groups in the structure CH3
groups; Met-8 neighboring
carbonyl has lowest shift than ester
Met-10
▶ doublet of doublets (cca 8.0 ppm) proton
signal splitted by two
neighbors - H-4
▶ two doublets in interaction with H-4 based
on the J-interaction: doublet
with larger J-constant belongs to
close proton - H-3, smaller
J-constant - more distant proton -
H-6
1D 1
H NMR spectrum of cinnamic acid
1
2
6
3
5
4
7
8
9 OH
OH
H
1D 1
H NMR spectrum of cinnamic acid
1
2
6
3
5
4
7
8
9 OH
OH
H
2,6 3,5
7 4
8
Notes:
▶ H-8 - doublet with large coupling, in
range of shifts of protons on double
bond, integral = 1
▶ H-7 - doublet with the same coupling
like doublet H-8, deshielded due to
-M effect of carboxyl and due to
nearby aromatic ring
▶ more intensive signal between 7.7
and 7.8 ppm has integral: 3-1=2
protons - H-2,6, symmetrical, highest
shift due to -M effect of substituent in
ortho position on aromatic ring
▶ signal with integral = 3 around 7.5
ppm - less intensive signal - only one
proton, highest shift due to -M effect
of substituent in para position - H-4;
more intensive signal with highest
shift - H-3,5
Draw approximate 1D 1
H NMR spectrum of the
following compound
Draw approximate 1D 1
H NMR spectrum of the
following compound
Notes:
▶ H-2 - meta- and ortho- interaction
with H-1 a H-3 - doublet of doublets
▶ H-1 - only meta- interaction with H-2
- smaller coupling than H-3 in orthointeraction
with H-2
▶ chemical shifts are result of overall
effects of substituents on the
aromatic ring
1D 1
H NMR spectrum of ethyl glutarate
1D 1
H spectrum of ethyl glutarate
2
3
4
1
Notes:
▶ symmetrical molecule - equivalent
groups will give rise to only one
signal
▶ splitting corresponds to n+1 rule
▶ signal integrals correspond to
number of protons in groups
H-1:H-2:H-3:H-4 in the ratio 6:4:4:2
▶ chemical shifts depend on chemical
environment of atoms
1D 1
H NMR spectrum of benzyl butyrate
1D 1
H NMR spektrum benzylbutyrátu
5,6,7
4
3
2
1
Notes
▶ highest shift - aromatic ring, which is
flexible - H-5, H-6, H-7 are under one
signal, integral value corresponds to
five protons
▶ lowest shifts - alifatic chain H-1, H-2
a H-3: H-1 - integral equals to three
protons, splitted only by H-2 to
triplet; H-2 - integral equals to two
protons, splitted by both H-1 and H-3
to triplet of quartets, which is due to
similar J-coupling values fused into
sextet; H-3 - integral equals to two
protons, splitted by H-2 to triplet
▶ H-4 - integral equals to two protons,
isolated signal - singlet, highest shift
among all alifatic protons due to
neighboring carboxyl and aromatic
ring
:
▶ lowest shift - methyl H-3, splitted due
to neighboring stereogenic center
C-2
▶ last splitted signal - H-2 - splitted by
H-3 to quartet, highest shift due to
neighboring carboxyl groups
▶ two singlets - highest shift H-4 next
to carboxylic oxygen; lowest shift H-1
next to carboxylic carbon
▶ integrals corresponds to number of
protons
Notes:
▶ highest shift - NH, least intensive
and broad signal because there is
dynamical exchange of the proton
with the solvent, it is visible in the
spectrum thanks to CDCl3 used as
solvent
▶ lowest shifts - alifatics - signal at 1.5
ppm splitted to triplet - methyl H-6
splitted by H-5; singlet around 2 ppm
- methyl H-7 - isolated, highest shift
than H-6 thanks to nitrogen; quartet
at 4 ppm - H-5 - splitted by methyl
H-6, highest shift thanks to oxygen
▶ two doublets in aromatic region
around 7 ppm - H-1,4 a H-2,3 symmetrical,
shifts are resulting from
effects of both substituents on
aromatic ring
1D 1
H NMR spectrum of cartilagineal
1D 1
H NMR spectrum - cartilagineal
Notes:
▶ highest shift - H-2 - proton of aldehydic
group, splitted to doublet with J = 2 Hz
(small value, interacting partner is
relatively far away)
▶ the same J = 2 Hz belongs to doublet of
doublets of doublets around 6.5 ppm,
other Js: J = 1 Hz and J = 15.5 Hz three
J-constants - three partners - H-3
▶ large J-value 15.5 Hz suggests near
neighbor - other signal with the same
constant is doublet of doublets around 7
ppm - H-4
▶ last constant of multiplet at 6.5 ppm - J
= 1 Hz - partner distant from H-3: either
H-1 or H-5, the same J- constant
belongs to doublet of doublets at 4,5
ppm - two constants, two partners which
is not the case for H-1 - therefore signal
at 4,5 ppm belongs to H-5
▶ just for check: both multiplets H-4 and H-5 are coupled with H-3 and with each other as well (J = 8.5 Hz)
▶ the only singlet in the spectrum is isolated H-1
▶ last unasigned doublet of doublets (6,1 ppm) must be H-6 because it is the only proton from the trio H-6, H-7, H-8 with two
unequivalent neighbors - larger coupling comes from interaction with H-8 in trans position, smaller coupling comes from
interaction with cis oriented H-7
▶ signal of the methyl group is not present in this spectrum
Next session:
1D 13C-NMR spectra