Proton Nuclear Magnetic Resonance

(1H-NMR) Spectroscopy

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 1H-NMR Spectroscopy
Background and Theory

Fundamental principle
The energy required to cause nuclear spin flip is a function of the magnetic
environment of the nucleus.

•Protons, electrons, neutrons have “spin” (I)

•Motion of charged particle creates magnetic field
•In absence of external influence, magnetic poles (spin axis) randomly oriented
•Add external magnetic field (Bo): spins align

Bo
add magnetic field

No external magnetic field With external magnetic field

Spin alignment random Spins aligned
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 Background and Theory
Nuclear Spin Flip
•I = +1/2 parallel to Bo (lower energy); I = -1/2 antiparallel to Bo (higher energy)
•Addition of energy results in nuclear spin flip
Increasing energy

I = -1/2
Absorb energy
DE ~ 0.02 cal mol-1
Release energy = radio wave photons
(relaxation)
I = +1/2

Ground state Excited state

Nuclear spin parallel to Bo Nuclear spin antiparallel to Bo
Lower energy Higher energy

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 Background and Theory
Magnetic Field Controls DE
• DE influenced by magnetic field strength at nucleus

I = -1/2
Spin state energy

Small magnetic field  small DE

DE DE
Large magnetic field  large DE

I = +1/2

Magnetic field strength at nucleus

Energy required for spin flip (DE)


Information about magnetic field strength at nucleus

Information about chemical structure 4
 Background and Theory
The NMR Spectrum
•Spectrum = plot of photon energy versus photon quantity

NMR signal
Intensity of signal
(photon quantity)

Spin flip energy (photon energy)

Deshielded (downfield) Shielded (upfield)
Low magnetic field strength High magnetic field strength
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 Background and Theory
The NMR Spectrum

Nuclear: manipulation of nuclear spin

Magnetic: magnetic field strength influences DE

Resonance: tendency of a system to oscillate at maximum

amplitude at a certain frequency

NMR C O
X C O

1H nucleus = a proton  1H-NMR = proton NMR

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 Background and Theory
Spectrum  Structure

How do we deduce structure from NMR spectrum?

Information from NMR spectrum

•Number of signals  number of nonequivalent proton groups in molecule
•Position of signals (chemical shift)  magnetic environment of protons
•Relative intensity of signals (integration)  ratio of equivalent proton types
•Splitting of signals (spin-spin coupling)  proton neighbors

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 Number of Signals
Proton Equivalency
•NMR signal due to photon absorption
•Photon energy controlled by magnetic environment of nucleus
•Nuclei in same magnetic environment = equivalent
•Multiple magnetic environments  multiple signals
•Number of signals = number of equivalent proton sets

O H H
H H

Cl CN

Protons equivalent Protons not equivalent

One NMR signal Two NMR signals

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 Number of Signals
Proton Equivalency
How to test for equivalency?
•Equivalent = proton magnetic environments identical in every way
•Nonequivalent = proton magnetic environments not identical in one or more ways
•Easier to test for nonequivalency than for equivalency
•Models:
Build two copies; label protons in question
Superpose protons in question
If rest of molecule superposable then protons in question are equivalent

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 Number of Signals
Proton Equivalency

Proton Equivalency Examples

not equivalent not equivalent

H H H
rapid equilibrium
H C Cl H C C Cl

H H H

One signal Two signals ? equivalent

equivalent

•NMR = “slow camera”

•NMR detects only average if rotation is fast
•Thousands of H3C-CH3 rotations per second
•Ha, Hb, Hc appear equivalent
•In general single bond rotation in acyclic molecules allows equivalency
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 Number of Signals
Proton Equivalency

More Proton Equivalency Examples

H H F Cl H F

H C C OH H C C H H C C Cl

H H F Cl F Cl

Three signals Two signals One signal

H H H H
C C H
C C
H C C C H mirror plane H C C H
C C H C C
H H H H

Four signals One signal

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 Number of Signals
Proton Equivalency
Sample Spectra
•Verify what we have learned about equivalent protons
•How many signals in 1H-NMR spectra of these molecules?
H H

CH3

CH3 C CH2OH HO OH

CH3
H H

Three proton sets  three signals Two proton sets  two signals

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 Ringkasan sebelumnya :

•Atomic nucleus has spin, and therefore generates a magnetic field

•Nuclear spin axis can be parallel or antiparallel to external magnetic field (Bo)
•Spin parallel to Bo (I = +1/2) lower energy than spin antiparallel to Bo (I = -1/2)
•Energy difference between spin states (DE) controlled by magnetic field at nucleus
•Absorption of radio wave photon with energy = DE causes nuclear spin flip
•NMR spectrum = plot of photon energy (spin flip energy) versus photon quantity

Information from NMR spectrum

•Number of signals reveals number of equivalent protons
Equivalency: protons must be identical in all ways to be equivalent
Nonequivalency: protons can be different in just one way
Example: 1H-NMR spectrum of CH3CH2OH has three signals
•Position of signal (chemical shift)
•Relative intensity of signals (integration)
•Splitting of signals (spin-spin coupling)
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 Position of Signals
The Chemical Shift
How does spin flip energy relate to molecular structure?
•Spin flip energy depends on magnetic field strength:

I = -1/2
Spin state energy

Small magnetic field  small DE

DE DE
Large magnetic field  large DE

I = +1/2

Magnetic field strength at nucleus

•High magnetic field = higher spectral resolution (more spectral detail)

•Magnetic field strength varies between NMR spectrometers
•Need a scale that is independent of magnetic field strength
•Chemical shift: spin flip energy scale normalized to be independent of field strength
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 Position of Signals
The Chemical Shift
How does molecular structure influence chemical shift?
•Chemical shift  DE  magnetic field at nucleus
What contributes to magnetic field at nucleus?
•Earth’s magnetic field (weak: 0.3-0.6 gauss)
•Spectrometer’s magnetic field (strong: typically 94 kilogauss)
•Other atoms in molecule
•Electron cloud of nucleus in question shield it from external magnetic fields
Shielded: nucleus feels weaker magnetic field
Deshielded: nucleus feels stronger magnetic field

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 Position of Signals
The Chemical Shift
Intensity of signal
(photon quantity)

Reference point?
0.00 ppm (CH3)4Si
Tetramethylsilane (TMS)

15 ppm Spin flip

Chemical
energy shift
(photon
scale
energy) 0 ppm
(ppm)
Deshielded (downfield) Shielded (upfield)

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 Position of Signals
The Chemical Shift
•How does molecular structure influence chemical shift?
5.0 4.0 3.0 2.0 1.0 0.0 ppm

CH3OH 3.42 ppm

CH3Cl 3.05 ppm

CH3CH3 0.86 ppm

CH3Br 2.68 ppm

(CH3)4Si 0.00 ppm

1.0
EN of X in CH3-X

2.0 1.8
2.1

2.5 2.5
3.0
2.8
3.0

3.5 Conclusion:  EN of atoms near H  chemical shift

4.0
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4.0
 Position of Signals
The Chemical Shift

How does electronegativity influence chemical shift?

•Chemical shift related to magnetic field strength at nucleus
•Electron cloud shields nucleus from effects of Bo

H X H X H X H X

Increasing EN of X
Decreasing electron density around H
Less shielding
Higher chemical shift

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 Position of Signals
Characteristic Proton NMR Chemical Shifts (pp m)
RCH3 0.9 RCCH 2.5 ArH 6.5 - 8

RCH2R acyclic 1.3 RNHCH3 2–3 RCHO, ArCHO 9.5 – 11

RCH2R cyclic 1.5 RCH2X 3.5 RNH2 1–3

(X = C l, Br, I)

R3CH 1.5 – 2.0 RCH2NR2 2.3 – 2.7 ArNH2 3–5

R CH3 O
R
1.8 OCH3 3.8 R N 5–9
R R H

O
2.0 – 2.6 OCH2 3.3 – 4.1 ROH 1–5
R CH3

O
2.2 – 3.0 R2C=CH2 5.0 ArOH 4–7
CH2R
benzene
ring ArCH3 2.3 RCH=CR2 5.3 RCO2H 10 – 13

ArCH2R 2.6

Do not memorize chemical shifts. Table given on exams. 19

 Position of Signals
Notes On Characteristic Chemical Shifts Table

•Characteristic shifts are typical proton averages. Actual shifts may lie outside given range.
O O O

CH3 Typically 2.0-2.6 ppm CH3O CH3 2.01 ppm

CH3 2.59 ppm

Useful chemical shift trends

•RCH3 < RCH2R < R3CH EN of C (in R) > EN of H
•EN effects decrease with distance:
3.59 ppm 1.53 ppm

CH4 CH3OH CH3CH2OH CH3CH2CH2OH

0.23 ppm 3.39 ppm 1.18 ppm 0.93 ppm 3.49 ppm
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 Position of Signals
Avoid This Common Misconception
•Unlike IR peaks, we cannot assign NMR peaks based only on chemical shift
•Example:
2.2 ppm not always ArCH3

3.8 ppm not always ROCH3

Common exception
6.5-8.0 ppm usually
benzene ring protons

C=O stretch

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 Relative Intensity of Peaks
Integration

•Beer’s Law: amount of energy absorbed or transmitted proportional to moles of stuff present

•NMR: amount of radio wave energy proportional to peak area

•Measurement of peak areas = integration

∫ir I∫aac Newton

Inventor of calculu∫

•Relative intensities of NMR signals proportional to relative number of equivalent protons

•Integrals do not always correspond to exact number of protons
Example: integrals of 2:1 might be 2H:1H or 4H:2H or...

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 Sample Spectra
•Verify what we have learned about equivalent protons, chemical shifts, and integration
•Assign peaks to corresponding hydrogens:
H 4.19 ppm: integral = 1.0 (1 H)
H C OH 3.41 ppm: integral = 3.0 (3 H)
H CH3OH has 4 H

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 Sample Spectra
•Assign peaks to corresponding hydrogens:

OCH3
3.19 ppm: integral = 1.0 (6 H)
H3C C OCH3 1.33 ppm: integral = 1.0 (6 H)
CH3 C5H12O2 has 12 H
Two equal integrals
Two groups of equivalent H

Smallest integral often set = 1

Integration gives proton ratio

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 Sample Spectra
•Assign peaks to corresponding hydrogens:

3.55 ppm: integral = 1.0 (4 H)

CH3OCH2CH2OCH3 3.39 ppm: integral = 1.5 (6 H)
Two groups of equivalent H
Two unequal integrals
C4H10O2 has 10 H
10 H / (1.0 + 1.5) = 4 H per unit

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 Sample Spectra
•Assign peaks to corresponding hydrogens:

CH3CH2Br
Three peaks!

Four peaks!

Homework
•Why the extra peaks? Hint: think about spin and magnetic fields 26
Proton Nuclear Magnetic Resonance
(1H-NMR) Spectroscopy Part 3
Lecture Supplement:
Take one handout from the stage

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 1H-NMR Spectroscopy Part 2 Summary
Information from NMR Spectrum
•Number of signals  how many sets of equivalent protons
•Position of signals (chemical shift)  magnetic environment of nucleus
Deshielding by electronegative atoms  higher chemical shift
•Relative intensity of signals (integration)  how many hydrogens per signal
Integrals give proton ratio; not always equal to absolute proton count (i.e., 1.5:1)
•Splitting of signals (spin-spin coupling)
Example:
3.55 ppm: integral = 1.0 4 H
CH3OCH2CH2OCH3
3.39 ppm: integral = 1.5 6 H
Two groups of equivalent H
Two unequal integrals
C4H10O2 has 10 H
10 H / (1.0 + 1.5) = 4 H per unit

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 Signal Splitting three lines
triplet
1H-NMR spectrum of CH3CH2Br has more details...

Signals
3.43 ppm: are split
integral = 1.0 2 H
CH3CH2Br 1.68 ppm: integral = 1.5 3 H
Two unequal integrals
5 H / (1.0 + 1.5) = 2 H per unit
four lines
quartet

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 Signal Splitting
What is the origin of signal splitting?
Each line in signal...
...has slightly different chemical shift
...represents slightly different spin flip energy
...represents nucleus with slightly different magnetic environment

This nucleus has only one magnetic environment

A singlet

This nucleus has two magnetic environments

A doublet

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 Signal Splitting
How can one nucleus have different magnetic environments?
•Spin direction of adjacent nuclei

Ha C C Hb

Ha feels Bo + Hb
Bo
Ha feels Bo - Hb

NMR signal for Ha

•Ha feels two different magnetic environments
•Ha has two different spin flip DE
•Ha has two different (but very similar) chemical shifts
•Ha signal is split into a doublet

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 Signal Splitting
Some Useful Terms

Spin-spin coupling: one nuclear spin influences spin of another nucleus

Splitting: effect on NMR signal caused by spin-spin coupling

J
Coupling constant (J): spacing between lines in a splitting pattern

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 Signal Splitting
More Than One Neighbor
What is splitting when there is more than one neighbor?
Ha C C Hc

Hb

Ha feels Bo + Hb + Hc

Ha feels Bo - Hb + Hc
Bo
H feels B + H - H
} equal energy
a o b c
NMR signal for Ha
Ha feels Bo - Hb - Hc
1:2:1 because of energy state
•Ha has three different (but very similar) chemical shifts population probabilities
•Ha signal is split into a triplet

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 Signal Splitting
Rules and Restrictions

General rule: the signal for a proton with n neighbors is split into n+1 lines

Rules and Restrictions for Proton-Proton Spin-Spin Coupling

1. Only nonequivalent protons couple

X
•Hb couples with Hc
X Hb Hc Hd H
•Hb and Ha do not couple because they are equivalent
Ha C C C C H

H H H H •Hc and Hd do not couple because they are equivalent

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 Signal Splitting
Rules and Restrictions

2. Protons separated by more than three single bonds usually do not couple
Hb Hd •Ha couples with Hb
X •Ha couples with Hc
Ha C C C
•Ha does not couple with Hd
Hc

Pi bonds do not count toward this bond limit, but J may be too small to observe
free spacer
Hb Hc •Ha couples with Hb
C C •Ha couples with Hc
Ha C •Ha couples with Hd but J may be very small
Hd
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 Signal Splitting
Rules and Restrictions
2. Protons separated by more than three single bonds usually do not couple
Hd
•Benzene ring = one big free spacer
Hc F
•All benzene ring protons may couple with each other but J may be small
•Ha, Hb, Hc, and Hd all couple with each other
Hb Cl
•Jad may be too small to observe
Ha

Benzene ring is a “gated community:” it blocks some coupling that we expect to observe

H X
CH3

X
CH2CH3

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 Signal Splitting
Rules and Restrictions

3. Signals for O-H and N-H are usually singlets

H H

singlet H2N C C OH singlet

H H

triplet triplet

•Splitting of O-H or N-H protons may be observed in rare circumstances

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 Sample Spectra
•Verify what we have learned about equivalency, chemical shifts, integration, and
splitting patterns
•Assign peaks to corresponding hydrogens in structure

BrCH2CH2CH3 3.39 ppm (triplet; integral = 1.0) 2 H

1.87 ppm (sextet; integral = 1.0) 2 H
1.03 ppm (triplet; integral = 1.5) 3 H

7 H / (1.0 + 1.0 + 1.5) = 2 H per unit

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 Sample Spectra
•Assign peaks to corresponding hydrogens in structure

Br

H3C C CH3
3.79 ppm (septet; integral = 1.0) 1H
H 1.31 ppm (doublet; integral = 6.0) 6 H

7 H / (1.0 + 6.0) = 1 H per unit

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 Sample Spectra
•Assign peaks to corresponding hydrogens in structure
5.66 ppm (multiplet; integral = 1.0) 2 H
H H
1.98 ppm (multiplet; integral = 2.0) 4 H
C H
H2C C 1.16 ppm (multiplet; integral = 2.0) 4 H
H2C C
C H 10 H / (1.0 + 2.0 + 2.0) = 2 H per unit
H H

Multiplet: a splitting pattern

that is too complex to decipher

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 Non-First Order Splitting
Why Is Cyclohexene Splitting Not Simple?

First order splitting: all J values in a splitting pattern are equal

•n+1 rule obeyed; “normal” doublets, triplets, etc. result

Non-first order splitting: J values in a splitting pattern are unequal

•More complex splitting patterns result

Example:
Hb

Ha C C Hc Jab = Jac Jab ≠ Jac

“normal” triplet doublet of doublets

For Chem 14C we predict J values equal and “normal” coupling results. Exceptions are plentiful.

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Proton Nuclear Magnetic Resonance
(1H-NMR) Spectroscopy Part 4
Lecture Supplement:
Take one handout from the stage

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 1H-NMR Spectroscopy Part 3 Summary
Information from NMR Spectrum
•Number of signals  how many sets of equivalent protons
•Position of signals (chemical shift)  magnetic environment of nucleus
Deshielding by electronegative atoms  higher chemical shift
•Relative intensity of signals (integration)  how many hydrogens per signal
Integrals give proton ratio; not always equal to absolute proton count (i.e., 1.5:1)
•Splitting of signals (spin-spin coupling)
•The signal of a proton with n neighbors is split into n+1 lines (first order coupling)
Example: CH3CH2Br CH3 is a triplet, CH2 is a quartet
More complex patterns (non first-order coupling) are common

Splitting rules
•Only nonequivalent hydrogens couple with each other
•Hydrogens can be at most three single bonds distant
•Pi bonds and benzene rings are “free spacers”
•Benzene ring “gated community”
•OH, NH usually not split

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 Sample Spectra
Effects of Pi Electron Clouds: Vinyl Protons (C=C-H)

H H 5.83 ppm (doublet of doublets; 1H)

C C 4.88 ppm (multiplet; 2 H)
H C(CH3)3
1.00 ppm (singlet; 9 H)

•Vinyl H splitting often not first order

•Pi electron cloud causes deshielding, downfield shift
•Shift effect by pi electrons = magnetic induction

Three doublets of doublets

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 Sample Spectra
Benzene Ring Protons

H H 10.00 ppm (singlet)

H
7.87-7.56 ppm (multiplet)
C H

H H

9.5-11 ppm 6.5-8.0 ppm

•Magnetic induction causes benzene ring proton chemical shifts ~6.5-8.0 ppm
•Magnetic induction by C=O causes aldehyde proton chemical shift ~9.5-11 ppm
•Due to long range coupling, benzene ring proton signals often multiplets
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 Sample Spectra
Benzene Ring Protons
Benzene ring proton signals can be deceptively simple...

CH3 •7.2 ppm = singlet?

•Benzene ring protons not equivalent

When chemical shifts very similar

J  0; splitting disappears

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