organic chemistry laboratory building a toolset for the identification of organic compounds...

Organic Chemistry LaboratoryBuilding A Toolset

ForThe Identification of Organic Compounds

04/19/23 1

Physical PropertiesMelting PointBoiling PointDensitySolubilityRefractive Index

Chemical TestsHydrocarbons

AlkanesAlkenesAlkynes

HalidesAlcoholsAldehydesKetones

SpectroscopyMass

(Molecular Weight)Ultraviolet

(Conjugation, Carbonyl)

InfraredFunctional Groups

NMR(Number, Type, Location of protons)

Gas Chromatography(Identity, Mole %)

Spectroscopy

The Absorption of Electromagnetic

Radiation and the use of the Resulting

Absorption Spectra to Study the

Structure of Organic Molecules

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SpectroscopySpectroscopy Types:

Mass Spectrometry (MS) –Hi-Energy Electron-Beam Bombardment

Use – Molecular Weight, Presence of Nitrogen, Halogens

Ultraviolet Spectroscopy (UV) – Electronic Energy States

Use – Conjugated Molecules; Carbonyl Group, Nitro Group

Infrared Spectroscopy (IR) – Vibrational & Rotational Movements

Use – Functional Groups; Compound Structure

Nuclear Magnetic Resonance (NMR) – Magnetic Properties of Nuclei

Use – The number, type, and relative position of protons (Hydrogen nuclei) and Carbon-13 nuclei

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The Electromagnetic Spectrum

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MicrowaveInfraredX-RayVacuum

UV

VisibleNear Ultraviolet

VibrationalInfrared

NuclearMagnetic

Resonance

Radio Frequency

400 nm200 nm 800 nm 2.5 15

1 m 5 m

Blue Red

Cosmic&

Ray

0.01 nm

3 x 1019 Hz 3 x 1016 Hz 2 x 1013 Hz

10 nm 30 cm

1 x109cm-1

0.002 cm-1

10 cm-1 3 cm-1 0.01 cm-1

1 mm

Frequency ()

Energy (E)

High

High Low

Low

Wavelength ()Short Long

1 x107cm-1 5 x104cm-1

2.5 x104cm-1

1.25 x104cm-1

667cm-1

4 x103cm-1

6 x 107 Hz

3 x 108 Hz

1.5 x 1015 Hz 1 x 109 Hz3 x 1011 Hz

1.2 x 1014 HzFrequency

Wave Number

Wavelength

NMR

Nuclear Magnetic Resonance Spectroscopy

NMR

04/19/23 5

NMR Nuclear Magnetic Resonance Spectroscopy (NMR)

Nuclear Spin Nuclear Spin State Magnetic Moments Quantized Absorption of Radio Waves Resonance Chemical Shift Chemical Equivalence Integrals (Signal Areas) Chemical Shift - Electronegativity Effects Chemical Shift - Anisotropy (non-uniform) effects

of pi bonds Spin-Spin Splitting

04/19/23 6

NMR NMR

NMR is an instrumental technique to determine the number, type, and relative positions of certain Nuclei in a molecule

NMR is concerned with the magnetic properties of these nuclei

Many Nuclei types can be studied by NMR, but the two most common nuclei that we will focus on are Protons (1H1) and Carbon-13 (13C6)

The magnetic properties of NMR suitable nuclei include: Nuclear Magnetic Moments Spin Quantum Number (I) Nuclear Spin States Externally Applied Magnetic Field Frequency of Angular Precession Absorption of Radio Wave Radiation - Resonance

04/19/23 7

NMR The Magnetic Properties

Many atomic nuclei have a property called “Spin” Since all nuclei have a charge (from the protons in the

nucleus), a spinning nuclei behaves as if it were a tiny magnet, generating its own Magnetic field

The Magnetic Field of such nuclei has the following properties – Magnetic Dipole, Magnetic Moment and Quantized Spin Angular Momentum

The Magnetic Moment (μ) of a nuclei is a function of its Charge and Spin and is defined as the product of the pole strength and the distance between the poles

Only Nuclei with Mass & Atomic number combinations of Odd/Odd, Odd/Even, Even/Odd possess “Spin Properties,” which are applicable to NMR

Note: Nuclei with a Mass & Atomic number combination of

Even/Even do not have “Spin” and are not useful for NMR

04/19/23 8

NMR Nuclear Spin States

Nuclei with spin (Magnetic Moment, Quantized Spin Angular Momentum, Magnetic Dipole) have a certain number of “Spin States.”

The number of “Spin States” a nuclei can have is determined by its “Spin Quantum Number I,” a physical constant, which is an intrinsic (inherent) property of a spinning charged particle.

The Spin Quantum Number (I) is a non-negative integer or half-integer (0, 1/2, 1, 3/2, 2, etc.).

The Spin Quantum Number value for a given nuclei is associated with the Mass Number and Atomic Number of the nuclei. Odd Mass / Odd Atomic No - 1/2, 3/2, 5/2 Spin Odd Mass / Even Atomic No - 1/2, 3/2, 5/2 Spin Even Mass / Even Atomic No - Zero (0) Spin Even Mass / Odd Atomic No - Integral (1, 2, 3)

Spin04/19/23 9

NMR Nuclear Spin States (Con’t)

The number of allowed Spin States for a nuclei is: 2I + 1with integral differences ranging from +I to -I

Ex. For I = 5/2 2I + 1 = 2 * 5/2 + 1 = 5 + 1 = 6

Thus, Spin State Values = 5/2, 3/2, 1/2, -1/2, -3/2, -5/2The Spin Quantum number (I) for either a Proton (1H1) or a Carbon-13 (13C6) nuclei is 1/2

Thus, the number of Spin States allowed for either aProton (1H1) or a Carbon-13 (13C6) nuclei is:

[2 * ½ + 1 = 1 + 1 = 2]

Therefore, the two spins states for either nuclei are:

+ 1/2 & - 1/204/19/23 10

NMR Nuclear Spin States (Con’t)

In the absence of an applied Magnetic field, all the spin states ( + ½ & - ½ ) of a given nuclei are of equivalent energy (degenerate), equally populated, and the spin vectors are randomly oriented

When an external Magnetic Field is applied, the degenerate spin states are split into two opposing states of unequal energy

+ 1/2 spin state of the nuclei is aligned with the applied magnetic field and is in a lower energy state

- 1/2 spine state of the nuclei is opposed to the applied magnetic field and is in a higher energy state

There is a slight majority of the lower energy (+1/2) nuclei

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NMR Two Allowed Spin States for a Proton

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Direction of an Externally Applied Magnetic Field (Ho)

Spin +1/2Aligned

Spin -1/2Opposed

- 1/2 Opposed to Field

+ 1/2 Aligned with Field

E

NoField

Externally AppliedMagnetic Field Ho

Ho

+1/2 Aligned

-1/2 Opposed

Alignments

Ho

Eabsorbed = (E-1/2 state - E+1/2 state) = h

E = f(Ho)The stronger the applied magnetic field (Ho),

the greater the energy difference between the spin states

E

NMR Applied Magnetic Field, Frequency of Angular Precession

Under the influence of an externally applied magnetic field, Nuclei with “Spin Properties,” such as Protons & Carbon-13, begin to Precess about the axis of spin with Angular Frequency ω, similar to a toy top

The Frequency which a proton precesses is directly proportional to the strength of the applied magnetic field

For a proton in a magnetic field of 14,100 gauss (1.41 Tesla), the Frequency of Precession is approximately 60 MHz

That same proton, in a magnetic field of 23,500 gauss (2.35 Tesla), will have a Frequency of Precession of approximately 100 MHz

The stronger the applied magnetic field, the higher the Frequency of Precession and the greater energy difference between the +1/2 and -1/2 spin states

04/19/23 13

NMR NMR Spectrometers

NMR spectrometers are rated according to the frequency, in MHz, at which a proton precesses - 60 MHz, 100 MHz, 300 MHz, 600 MHz, or even higher.

Continuous Wave (CW) NMR instruments are set up so that the externally applied magnetic field strength is held constant while a RF oscillator subjects the sample to the full range of Radio Wave frequencies at which protons (or C-13 nuclei) resonate.

In Fourier Transform (FT) NMR instruments, the RF oscillator frequency is held constant and the externally applied magnetic field strength is changed.

Most NMR instruments today are of the Continuous Wave type

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NMRTypically, Continuous Wave (CV) Spectrometers are used in which the externally applied magnetic field is held constant and RF Radio Oscillator applies a full range of frequencies at which protons or C-13 nuclei resonate

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NMR Energy Absorption, Resonance

If long wave radio radiation (1-5 m) is applied from a RF Oscillator to a sample under the influence of a strong externally applied magnetic field, and the frequency of the oscillating electric field component of the incoming radiation matches the Angular Frequency of Precession of the nuclei, the two fields couple and energy is transferred from the incoming radiation to the protons

This causes the nuclei with +1/2 spin state to absorb energy and change to the -1/2 spin state

When Energy is absorbed at specific frequencies it is referred to as being “Quantized”

When a proton absorbs a radio wave, whose frequency matches its Angular Frequency of Precession, it is said to be in “Resonance” with the incoming signal

04/19/23 16

NMR Electron Density, Frequency of Angular Precession

Protons exist in a variety of chemical and magnetic environments, each represented by a unique electron density configuration

Under the influence of a strong externally applied magnetic field, the electrons around the proton are induced to circulate, generating a secondary magnetic field (local diamagnetic current), which acts in opposition (diamagnetically) to the applied magnetic field

This secondary field shields the proton (diamagnetic shielding or diamagnetic anisotropy) from the influence of the applied magnetic field

Recall from slide # 13 that the Angular Frequency of Precession is directly proportional to the applied Magnetic Field strength

04/19/23 17

NMR Electron Density, Frequency of Angular Precession

(Con’t) As the shielding of the proton increases (increased

electron density) it diminishes the net applied magnetic field strength reaching the proton; thus the Angular Frequency of Precession is lower

If the electron density decreases, more of the applied magnetic field strength impacts the proton and it will precess at a higher Angular Frequency

Thus, each proton with a unique electron density configuration will “Resonate” at a unique “Frequency of Angular Precession

In a 60 MHz NMR Spectrometer all protons will resonate at a magnetic field strength of approximately 60 MHz, but each unique proton will resonate at its own unique frequency, with differences among unique protons of only tens of Hertz in a field of 60 MHz

04/19/23 18

NMR NMR Spectra – Fourier Transform vs. Continuous

Wave Fourier Transform

In a Fourier Transform (FT) NMR, the spectrum produced is a plot of the magnetic field strength – representing the frequency of the resonance signal – on the X-axis – versus the intensity of the absorption on the Y-Axis.

Each signal – consisting of one or more peaks – represents the “Resonance Frequency” of a particular type of proton with a unique chemical & magnetic (electron density) environment.

04/19/23 19


Wave Fourier Transform (Con’t)

As the pen of the recorder moves from left to right, the value recorded on X-axis of the NMR spectrum represents small increments of increasing magnetic field strength.

The right side of the NMR Spectrum is referred to as being “Upfield” (higher magnetic field strength).

The left side of the NMR Spectrum is referred to as being “Downfield” (lower magnetic field strength).

04/19/23 20


Wave (Con’t) Continuous Wave

In a Continuous Wave NMR, the spectrum produced is a plot of the RF Radio Oscillator Frequency versus the intensity of the absorption on the Y-Axis.

As before, each signal – consisting of one or more peaks – represents the “Resonance Frequency” of a particular type of proton with a unique chemical & magnetic (electron density) environment.

As the pen of the recorder moves from left to right, the value recorded on X-axis of the NMR spectrum represents a decreasing RF Oscillator Frequency (Resonance Frequency)

04/19/23 21


Wave (Con’t) Continuous Wave (Con’t)

The Signals on the right side of the NMR Spectrum represent protons (C-13 nuclei) that Resonate at lower frequencies.

The Signals on the left side of the NMR Spectrum represent protons (C-13 nuclei) that Resonate at higher frequencies.

04/19/23 22

NMR NMR Spectra – FT or CW: the spectrum looks the same

A FT or CW spectrometer will produce the same spectrum. The peaks on the right side of the spectrum represent

those protons (or C-13 nuclei) that resonate at the highest externally applied magnetic field strength and the lowest frequency

This statement would appear to be in conflict with the statement on Slide #13:

“The Frequency which a proton Precesses is directlyproportional to the strength of the applied magnetic field”

This apparent conflict is resolved by consideration of the influence of the secondary magnetic field set up by the Diamagnetic Current from circulating valence electrons.

This magnetic field opposes the externally applied field reducing the effect of the applied Magnetic Field on the proton, which in turn lowers the Resonance Frequency

04/19/23 23

NMR NMR Spectra – FT or CW: the spectrum looks the same

(Con’t)

The protons that resonate and produce signals on the right side of the NMR Spectrum (up field) have higher electron density shields than protons that resonate downfield

The net effect of the difference between the externally applied magnetic field and the amount prevented from actually reaching the proton results in a significantly reduced Resonance Frequency

As the NMR spectrum moves from right to left, the electron density about the various proton environments is decreasing, resulting in more of the externally applied magnetic field getting through to the proton

As this net magnetic force is increasing downfield toward the left side of the spectrum, the Resonance Frequency increases in conformance with the statement on Slide #13

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NMR NMR Spectra – Background Summary

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In a continuous Wave NMR, the strength of the externally applied magnetic field is held “constant”.

Protons that produce signals on the right side of the NMR spectrum have a higher amount of valence electron shielding.

The Magnetic Field produced by circulating valence electrons (Diamagnetic Current) opposes the externally applied Magnetic Field.

The Diamagnetic Field diminishes the amount of Applied Magnetic Field reaching the proton.

The net amount of magnetic force impacting the proton is reduced resulting in a lower Resonance Frequency.

As the Electron Density about a proton decreases downfield, the Resonance Frequency increases because more of the applied Magnetic Field impacts the Proton.

Applied Magnetic Field Strength – Ho is held constant

Shielding of Proton by Valence Electrons

Diamagnetic (Anisotropic) Magnetic Field StrengthProduced by Circulation of Valence Electrons

Net Magnetic Field Impacting Proton

Frequency of Angular Precession(Resonance Frequency)

Ab

sorp

tion

Signal

TMS

PPM 013

Applied Radio Frequency - RF

NMR NMR Spectra – The Chemical Shift

The differences in the applied Magnetic Field strength (Angular Frequency of Precession) at which the various proton configurations in a molecule Resonate are extremely small

The differences amount to only a few Hz (parts per million) in a magnetic field strength of 60, 100, 300, .... MHz (megahertz)

It is difficult to make direct precise measurements of resonance signals in the parts per million range

04/19/23 26

NMR NMR Spectra – The Chemical Shift

The typical technique is to measure the difference between the Resonance signals of various sample nuclei and the Resonance signal of a standard reference sample (see slides 25 & 26)

A parameter, called the “Chemical Shift” (), is computed from the observed frequency shift difference (in Hz) of the sample and the “standard resonance signal” divided by the applied Magnetic Field rating of the NMR Spectrometer (in MHz)

Thus, the Chemical Shift () is field-independent of the Magnetic Field rating of the instrument

04/19/23 27

NMR NMR Spectra – The Chemical Shift (Con’t)

The Chemical Shift is reported in units of:

“Parts Per Million” (ppm)

04/19/23 28

Ex: If a proton resonance was shifted downfield 100 Hz relative to the standard in a 60 MHz machine, the chemical shift would be:

= 100 Hz / 60 MHz = 1.7 ppm

By convention, the Proton Chemical Shift values increase from right to left, with a range of 0 – 13

In other words: Chemical Shift values decrease with increasing Magnetic field strength or Chemical Shift values increase with increasing Resonance frequency!

Observed Shift from TMS(Hz) HzChemical Shift = = = PPM

60 MHz MHz

NMR NMR Spectra – The Internal Reference Standard

The universally accepted standard used in NMR is: Tetramethylsilane (TMS)

The 12 protons on the four carbon atoms have the same chemical and magnetic environment and they resonate at the same field strength, i.e., one signal (1 peak) is produced

The protons are highly protected from the applied magnetic field because of high valence electron density

The strength of the Diamagnetic Field generated by the valence electrons in TMS is greater than most other organic compounds

04/19/23 29


Thus, little of the applied magnetic field gets through to the TMS protons reducing the Frequency of Angular Precession (Resonance Frequency) to a value that is lower than most other organic compounds.

For most all other Proton environments, the electron density is less than TMS and slightly more of the applied magnetic field gets through to the protons resulting in a slightly higher frequencies of Angular Precession.

04/19/23 30


The TMS signal appears on the far right hand side of the X-axis.

Small amount TMS in the sample produces large signal

By definition, the Chemical Shift value for TMS is

“0 ppm”

Thus, most all other protons will have Chemical Shifts > 0 and will be downfield from the TMS signal.

04/19/23 31

NMR NMR Spectra – Simple Example

04/19/23 32

All six protons of Ethane are chemically and magnetically equivalent and all resonate at the same frequency producing one signal consisting of “one” peak, i.e., a singlet.

An NMR Signal can consist of one or more “peaks”

Multiple peaks are produced by a phenomenon called “spin-spin splitting”

Note – See slides 53-62 for a discussion of Spin/Spin Splitting

For the chemically equivalent protons in Ethane there is no splitting, thus the signal consists of “one” peak, a singlet

See next slide for more NMR Spectrum examples, showing basic splitting patterns

Typical location (1 ppm) of resonance signal for Methyl group protons not under the influence of an electronegative group (see slide )

Note the “6” at the top of the signal

This is the peak integration value and represents the electronically integrated area under the signal curve and is proportional to the number of Protons generating the signal, i.e., Ethane has 6 chemically and magnetically equivalent protons

See slides 36-39 for a discussion of signal integration

Ab

sorp

tion

Signal(singlet)

Chemical Shift (PPM)

13 12 11 10 9 8 7 6 5 4 3 2 1 0

Ethane TMS

(6)

NMR NMR – Simple Examples

04/19/23 33

The Six (6) equivalent Methyl Protons arerepresented as a Triplet at about 1 ppm.

The 3 Triplet peaks are produced by Spin-Spin splitting based on the 2 protons attached to the Methylene Group (n + 1 rule).

Chemical Shift (PPM)

Propane The Two (2) equivalent Methylene Protonsare represented as a Septet at about 2 ppm.

The 7 Septet peaks are produced by spin-spin splitting based on the 6 protons attached to the two Methyl groups (6 +1 = 7).

13 12 11 10 9 8 7 6 5 4 3 2 1 0

(6)(2)

TMS

Toluene

3 equivalent Protons onMethyl Group Carbon attached to a Benzene

ring Carbon that has no attached protons.

Therefore, the signal is a singlet with no

splitting.

5 unsubstituted Protonson Benzene ring are notequivalent, producing

complex spitting patterns typical of the

resonance structures in aromatic rings.

See slides 60-65.

13 12 11 10 9 8 7 6 5 4 3 2 1 0

(3)(5)The Methyl group donateselectrons to Benzene ringactivating it. The Methylprotons have less electrondensity (deshielded), thus,the Chemical Shift is moveddownfield.

NMR Chemical Equivalence

Protons in a molecule that are in chemically identical environments will often show the same chemical shift

Protons with the same chemical shift are chemically equivalent

Chemical equivalence can be evaluated through symmetry

Protons in different chemical environments have different chemical shifts, i.e. a signal is produced for each.

04/19/23 34

Chemicals giving rise to 1 NMR signalChemicals giving rise to 2 NMR signalsH

H H

H

H

H

H H

H

CH3

H

CH3

O

CH3 C O CH3

CH3 O CH2ClCH3 CH3

C

O

Cyclopentane

Acetone

Benzene Methyl Acetate 1,4 dimethyl benzene (p-xylene)

1-Chloro Methyl Ether

NMR An Isomer Example – C5H12O

04/19/23 35

2-Dimethyl Propanol

Signals Rel Area Value of Signal

a ~ 1 9

b > 2 2 c ~ 2 1

t-Butyl Methyl Ether

Signals Rel Area Value of Signal

a ~ 1 9

b >>1 3

9 protons on 3 Methyl groups are equivalent and are not under the influence of the electronegative OH group.2 protons on Methylene group are equivalent and are influenced by electronegative OH group.The proton on OH group is concentration and hydrogen bonding dependent. Location on spectrum variable.Note: All signals are “singlets”, i.e., no adjacent protons to produce spin-spine splitting.

3 2 0.9 0

tms

a

9

c1

b2

3 2 1 0

tms

a

9

b3

(a)

CH3

CH3

CH3 C O CH3

(b)(a)

(a)

CH3 C CH2OH

CH3

CH3

(a)

(b) (c)(a)

(a)

9 protons on 3 Methyl groups are equivalent and not under the influence of electronegative group.3 protons on single Methyl groups are equivalent and are under influence of electronegative oxygen.

NMR Integrals (Signal Area)

An NMR spectrum also provides means of determining How Many of each type of proton the molecule contains.

The Area under each signal is proportional to the number of protons generating that signal.

In the Phenylacetone example below there are three (3) chemically distinct types of protons: Aryl (7.2 ppm), Benzyl (3.6 ppm), Methyl (2.1 ppm)

The three signals in the NMR spectrum would have Relative Areas in the ratio of 5:2:3.

Thus, 5 Aryl protons, 2 Benzyl protons, and 3 Methyl protons

04/19/23 36

2.1 ppm(3 protons)3.6 ppm

(2 protons)

7.2 ppm(5 protons)

Phenylacetone

NMR NMR Spectrum – Phenylacetone (103-79-7)

04/19/23 37

C9H10O

Methyl3 Protons

Methylene2 Protons

Ring5 Protons

NMR Integrals (Signal Area) (Con’t)

NMR Spectrometer electronically integrates the area under a signal and then traces rising vertical lines over each peak by an amount proportional to the area under the signal – see next slide.

The heights of vertical lines give RELATIVE numbers of each type of hydrogen.

Integrals do not always correspond to the exact number of protons,e.g., integrals of 2:1 might be 2H:1H or 4H:2H or...

Computation Draw Horizontal lines separating the adjacent signals. Measure vertical distance between the Horizontal

lines. Divide each value by the smallest value. Multiple each value by an integer >1 to obtain whole

numbers. See example computation on next Slide.

04/19/23 38

NMR Integrals (Signal Area) (Con’t)

NMR Spectrum – Benzylacetate (C9H10O2)

04/19/23 39

Peak 7.3 ppm (c) - (h1) 55.5 Div

Peak 5.1 ppm (b) - (h2) 22.0 Div

Peak 2.0 ppm (a) - (h3) 32.5 Div

55.5 div

22.0 div

= 2.52

22.0 div

22.0 div

= 1.00

32.5 div

22.0 div

= 1.48

2.52 : 1.00 : 1.48

5 : 2 : 3

c : b : a

Each value multiplied by “2”

to obtain integral values

h1

h2

h3(a)

(b)(c)

NMR Chemical Shift – Impact of Electronic Density

Valence Electrons In the presence of the applied magnetic field, the

valence electrons in the vicinity of the proton are induced to circulate (Local Diamagnetic Current) producing a small secondary magnetic field

The greater the electron density circulating about the nuclei, the greater the induced magnetic shielding effect

The induced magnetic field acts in opposition (diamagnetically opposed) to the applied magnetic field, thus shielding the proton from the effects of the applied field in a phenomenon called Local Diamagnetic Shielding or Diamagnetic Anisotropy

As the Diamagnetic Anisotropy increases, the amount of the applied magnetic field reaching the proton is diminished, decreasing the frequency of Resonance

04/19/23 40

NMR Chemical Shift - Anisotropy (non-uniformity)

For some proton types, the chemical shifts can be complicated by the type of bond present

Aryl compounds (benzene rings), Alkenes (C=), Alkynes (C ), and Aldehydes (O=CH) show anomalous resonance effects caused by the presence of electrons in these structures

The movement of these electrons about the proton generate secondary non-uniform (anisotropic) magnetic fields

The relative shielding and deshielding of protons in groups with electrons is dependent on the orientation of the molecule with respect to the applied magnetic field

04/19/23 41

NMR Chemical Shift - Anisotropy (non-uniformity)

(Con’t) The Diamagnetic Anisotropic effect diminishes

with distance In most cases, the effect of the Diamagnetic

Anisotropic effect is to Deshield the protons, increasing the Chemical Shift

In some cases, such as acetylene hydrogens, the effect of the anisotropic field is to shield the hydrogens, decreasing the Chemical Shift

In a Benzene ring , the electrons are induced to circulate around the ring by the applied magnetic field, creating a ring current, which in turn produces a magnetic field further influencing the shielding of the ring protons

04/19/23 42

NMR Chemical Shift - Anisotropy (non-uniformity) (Con’t)

The presence of ring current causes the applied magnetic field to become non-uniform (diamagnetic anisotropy) in the vicinity of the benzene ring

The effect of the anisotropic field is to further deshield the benzene protons, increasing the chemical shift

Thus, protons attached to the benzene ring are influenced by three (3) magnetic fields: Strong Applied Magnetic Field Local Diamagnetic Shielding by Valence Electrons Anisotropic Effect from the Ring Current

The net effect of the deshielding of the Benzene Ring protons is to increase the Chemical Shift far downfield to about 7.0 ppm

04/19/23 43

NMR Electron Density and Electronegativity

Protons in a molecule exist in many different electronic environments (Methyl group (CH3), Methylene group (CH2), bonds, unsubstituted Benzene ring Protons, Amino protons (NH), Hydroxyl protons (OH), etc.)

Each proton with a unique electron density configuration will have a unique Angular Frequency of Precession

The electron density of a given proton and thus, the frequency of precession, can be further influenced by the presence of electronegative groups in the vicinity of the proton

Electronegative groups (or elements) are electron withdrawing, pulling electron density away from the proton

04/19/23 44

NMR Chemical Shift – Impact of Electronegative Elements

The decrease in electron density about the proton results in a lower secondary magnetic field, a diminished shielding effect, an increase in the strength of the applied magnetic field reaching the nuclei, resulting in an increase in the precession frequency

Electronegative elements are electron withdrawing

When added to a carbon atom with protons attached, the Electronegative element withdraws electron density about the proton

Reducing electron density deshields the proton from the effect of the applied field, allowing more of the magnetic field to impact the proton

04/19/23 45

NMRChemical Shift – Impact of Electronegative Elements

(Con’t) Recall that Deshielding the proton increases the

Resonance Frequency producing a greater chemical shift, i.e., the resonance peak is moved downfield to the left on the spectrum

The chemical shift increases as the electronegativity of the attached element increases

Multiple substitutions have a stronger effect than a single substitution

Electronegativity also affects the Chemical Shift of Protons further down the chain. But the effect is diminished as distance from the Electronegative Element increases

04/19/23 46

NMR Chemical Shift – Impact of Electronegative

Elements

04/19/23 47

Compound CH3X CH3F CH3OH CH3Cl CH3Br CH3I CH4 (CH3)4SiElement X F O Cl Br I H SiElectronegativity of X 4.0 3.5 3.1 2.8 2.5 2.1 1.8Chemical Shift (ppm) 4.26 3.40 3.05 2.68 2.16 0.23 0

CH4 CH3OH CH3CH2OH CH3CH2CH2OH

0.23 ppm 3.39 ppm 1.18 ppm

3.59 ppm

0.93 ppm

1.53 ppm

3.49 ppm

Note: The Chemical Shift of the Proton increases as the distance from the Electronegative Oxygen increases.

NMR

04/19/23 48

Chemical Shift values of typicalProton environments and the effectsof Electronegative Elements on theChemical Shift.

12 11 10 9 8 7 6 5 4 3 2 1 0 (ppm)

CHCl3

-OH, -NH

TMS

H

CH2FCH2ClCH2BrCH2ICH2OCH2NO3

CH2ArCH2NR2

CH2SC C HCH2 C

O

CH2

C CH C C

C CH2 C

C CH3

Acids RCOOH 11.0 - 12.0 ppmAldehydes RCOH 9.0 - 10.0Phenols ArOH 4.0 - 7.0Alcohols ROH 0.5 - 5.0Amines RNH2 0.5 - 5.0Amides RCONH2 5.0 - 8.0Enols CH=CH-OH 15.0

Groups with variable chemical shifts(Protons attached to elements other than Carbon)

Methine (1H)

Methylene (2H)

Methyl (3H)

Effects of Electronegativity

F > O > Cl = N > Br > S > I

Electronegative Elements will pull electron density awayfrom the proton diminishing the electron density. Proton is exposed to increased effects of the applied magnetic field, which increases the frequency of absorbance (Chemical Shift) moving the Resonance Signal downfield to the left.

NMR General Regions of Chemical Shifts

04/19/23 49

12 11 10 9 8 7 6 5 4 3 2 1 0 (ppm)

TMSAldehydic

Aromatic & Heteroaromatic

Alkene

-Disubstituted Aliphatic

-Monosubstituted Aliphatic

Alkyne

-Substituted Aliphatic

Aliphatic Alicyclic (CH2, CH3)

Carboxylic

NMRApproximate Chemical Shifts Protons (1H1) Carbon (13C6)

04/19/23 50

Type of Proton Chemical Shift, (ppm)

a Chemical shifts of these protons vary in different solvents and with temperature

Type of Carbon Atom Chemical Shift , (ppm)

1o Alkyl, RCH3 0.8 - 1.02o Alkyl, RCH2R 1.2 - 1.43o Alkyl, R3CH 1.4 - 1.7Allylic, R2C C CH3 1.6 - 1.9 RKetone, RCCH3 2.1 - 2.6

OBenzylic, ArCH2-R 2.2 - 2.5

Acetylenic, RC CH 2.5 - 3.1Alkyl Iodide, RCH2I 3.1 - 3.3Ether, ROCH2R 3.3 - 3.9

Alcohol, HOCH2R 3.3 - 4.0

Alkyl Bromide, RCH2Br 3.4 - 3.6Alkyl Chloride, RCH2Cl 3.6 - 3.8

Vinylic, RC2 CH2 4.6 - 5.0

Vinylic, RC2 CH2-R 5.2 - 5.7

Aromatic, ArH 6.0 - 9.5Aldehyde, RCH 9.0 - 10.0 OAlcohol hydroxyl, ROH 0.5 - 6.0a

Amino, R NH2 1.0 - 5.0a

Phenolic, ArOH 4.5 - 7.7a

Carboxylic, RCOOH 11 - 12a

1o Alkyl, RCH3 0 - 402o Alkyl, RCH2R 10 - 503o Alkyl, RCHR2 15 - 50Alkyl Halide or Amine, C-X 10 - 65 Alcohol or Ether, C-O 50 - 90Alkyne, C 60 - 90Alkene, C = 100 - 170

Aryl, Ar- 100 - 170

Nitriles, -C N - 120 - 130 OAmides, -C - N - 150 - 180 OCarboxylic Acids, Esters, C O 160 - 185 OAldehydes, Ketones, -C - 182 - 215

C-

NMRFunctional Chemical Functional

ChemicalGroup Shift, ppm Group Shift,

ppm

04/19/23 51

TMS (CH3)4Si 0 AromaticAR – H 6.5 – 8.0

Cyclopropane 0 - 1.0 AR – C –H (benzyl) 2.3 – 2.7

Alkanes FluoridesRCH3 0.9 F – C – H 4.2 – 4.8R2CH2 1.3 ChloridesR3CH 1.5 Cl – C – H 3.1 – 4.1

ClAlkenes Cl – C – H 5.8

C = C – H 4.6 – 5.9C = C – CH3 1.5 – 2.5 Bromides

Br – C – H 2.5 – 4.0Alkynes

C C – H 1.7 – 2.7 IodidesC C – CH3 1.6 – 2.6 I – C – H 2.0 – 4.0

Nitroalkanes O2N – C – H 4.2 – 4.6

NMRFunctional Chemical Functional ChemicalGroup Shift, ppm Group Shift, ppm

04/19/23 52

Alcohols Carboxylic Acids

H – C – O – H 3.4 – 4 O

R – O – H 0.5 – 5.0 H – O – C – C – H 2.1 – 2.6

Phenols O

Ar – O – H 4.0 – 7.0 R – C – O – H 11.0 – 12.0

AminesR – NH2 0.5 – 4.0 Ketones

Ethers O

R – O – C - H 3.2 – 3.8 R – C – C – H 2.1 – 2.4

Acetals

R – O R Aldehydes

C 5.3 O

R – O H R – C – H 9.0 – 10.0

Esters Amides

O O

R – O – C – C – H 3.5 – 4.8 R – C – N – H 5.0 – 9.0

NMR Spin – Spin Splitting

In addition to the Chemical Shift and Signal Area, the NMR spectrum can provide information about the number of the protons attached to a Carbon atom.

Through a process called “Spin-Spin Splitting, a Proton or a group of equivalent Protons can produce “multiple” peaks (multiplets).

Protons on a Carbon atom are affected by the presence of Protons on nearby, generally adjacent atoms.

Spin - Spin splitting is the result of the interaction or coupling of the +1/2 & -1/2 spins of the protons on the adjacent carbon atoms.

Spin - Spin coupling effects are transferred primarily through the bonding electrons

04/19/23 53

NMR Spin – Spin Splitting (Con’t)

Those Protons on the adjacent Protons aligned with the applied magnetic field (+1/2 spin state), will transfer Magnetic Moment to, and thus augment, the strength of the magnetic field applied to the Proton sensing the adjacent Protons.

This increase in the magnetic field strength affecting the sensing Proton makes it more difficult for the “secondary” or “diamagnetic” field produced by the valence electrons to protect the proton; thus, the Proton is “deshielded” causing the Chemical Shift to increase slightly

04/19/23 54

NMR Spin – Spin Splitting (Con’t)

If the spins of the adjacent Protons are opposed to the magnetic field (-1/2 spin state), the strength of the applied magnetic field around the sensing proton is slightly decreased

With a reduced applied magnetic field strength, the secondary diamagnetic field is better able to “shield” the Proton from the applied field resulting in a slight decrease in the Chemical Shift (increased “Resonance Frequency”)

With 2 or more Protons on the adjacent Carbon atoms, there will be mixtures of +1/2 & -1/2 spins states producing unique Chemical Shift effects

04/19/23 55

NMR Each unique Proton or group of equivalent

Protons “senses” the number of Protons on the Carbon atom(s) next to the one it is bonded, and splits its resonance signal into n+1 signals, where “n” is the number of Protons on the adjacent Carbon atom(s)

The “n+1” value represents the number of unique combinations of the +1/2 and -1/2 spin states of the adjacent Protons

04/19/23 56

NMR Spin-Spin Splitting (Con’t)

04/19/23 57

1,1,2-Trichloroethane Tert-Butyl Methyl Ether(a)

(a)

(a) (b)

All protons chemically equivalent

(a) protons & (b) protons are separated by more than three (3) bonds

No signal splitting - 2 signals (a) & (b)

Possible spincombinations of adjacent protons

Net Spin+1 0 -1 1 2 1

+1/2 -1/2 1 1 Signal Intensity

0

TMS

b3H

a9H

NMR Spin-Spin Splitting – An example

04/19/23 58

1,1,2-Trichloroethane

NMR Spin - Spin Splitting - Multiplet Signal Intensities

04/19/23 59

Example Spectrum: Ethyl group

1.833.20

CH3 CH2

Note Relative Signal Intensities

Net Spin +3/2 +1/2 -1/2 -3/2

= spin +1/2

= spin -1/2

There are 3 times as many protons with+1/2 or - 1/2 spin arrangements than +3/2 & -3/2

Therefore, the signal intensities are greater.

1 6 15 20 15 6 1

1 5 10 10 5 1

1 4 6 4 1

1 3 3 1

1 2 1

1 1

1

Pascal’s Triangle

0 Singlet

1 Doublet

2 Triplet

3 Quartet

4 Quintet

5 Sextet

6 Septet

Intensity ratios derived from the n + 1 rule

Each entry is the sum of the two entriesabove it to the left and right.

The relative intensities of the outer signals in sextet & septet multiplets are very weak and sometimes obscured.

(a)

(a)

(b)

(b)

Intensity 1 3 3 1

No.AdjacentProtons

No.PeaksSeen Relative

Intensity

NMR Spin - Spin Splitting - Common Splitting Patterns

04/19/23 60

X CH CH Y (X Y)

CH2 CH

X CH2 CH2 Y (X Y)

CH3 C H

CH3 CH2

CH3

CHCH3

2 signals(see 1)

2 signals(see 1)

3 signals(see 2)

2 signal(see 1)

4 signals(see 3)

4 signals(see 3)

7 signals(see 6)

Singlet

Triplet

Doublet

Quartet

Quintet Sextet

Septet

No. signals produced based on the no. of adjacent protons

2 signals(see 1)

3 signals(see 2)

3 signals(see 2)

2 signals(see 1)

3 signals(see 2)

NMR Spin - Spin Splitting - Isomer Example

04/19/23 61

1-Chloropropane

2-Chloropropane

CH3 CH2 CH2 Cl(a) (b) (c)

ClCH3 CH CH3

(a)

(b)

(a)

3 signals

2 signals

Signal Rel Chem Rel Signal Neighbors Multiplicity Shift Area

a lowest 3 2 3 (Triplet) b middle 2 5 6 (Sextet) c highest 2 2 3 (Triplet)

0 ppm

0 ppm

abc

a

b Signal Rel Chem Rel Signal Neighbors Multiplicity Shift Area a lowest 6 1 2 (Doublet) b highest 1 6 7 (Septet)

NMR Spin - Spin Splitting - Coupling Constant

The Coupling Constant (J) is the spacing between the component signals in a multiplet.

The distance is measured on the same scale as the chemical shift (Hz or cycles per second (CPS)). Note: 60 Hz = 1 ppm in a 60 MHz instrument.

The Coupling Constant has different magnitudes for different types of protons

04/19/23 62

HHH H

C C

H

H

H H

H

H

H C C CH

CH

H

H

H

H

H

O

H

H

H

H

H

H

H

H

H

H

6-8 Hz

11-18 Hz

6-15 Hz

0-5 Hz

4-10 Hz

0-3 Hz

Ortho6-10 Hz

para1-4 Hz

meta0-2 Hz

8-10 Hz

a,a 8-14 Hza,e 0-7 Hze,e 0-5 Hz

cis 6-12 Hztrans 4-8 Hz

cis 2-5 Hztrans 1-3 Hz

5-7 Hz

NMR Magnetic Equivalence

04/19/23 63

They behave as an integral group.Protons attached to the same carbon atom and have the same chemical shift do not show spin-spin splitting.

These protons are coupled to the same extent to all other protons in the molecule.

They have the same Coupling Constant value J to the HA proton.

Protons that have the same chemical shift and are coupled equivalently to all other protons are magnetically equivalent and do not show spin-spin splitting.

In the spin-spin example of 1,1,2-Trichloroethane, the two (geminal) protons attached to the same carbon atom (HB & HC), do not split each other

H H

Cl C C Cl

Cl H

A B

C

H H

Cl C C Cl

Cl HC

BA

NMR Differentiation of Chemical and Magnetic

Equivalence

04/19/23 64

Br

CH3Br HA

HB

CH3

Cyclopropane Compound

Two geminal protons (HA & HB) are chemically equivalent, but not magnetically equivalent

Proton HA is on same side of ring as two halogens

Proton HB is on same side of ring as the two methyls

Protons HA & HB, therefore have different chemical shifts

They couple to one another and show spin-spin splitting

Two doublets will be seen for both HA & HB

Coupling Constant J for them is about 5 Hz

NMR Differentiation of Chemical and Magnetic Equivalence

(Con’t)

04/19/23 65

Geminal protons (HA & HB) are chemically equivalent, but not magnetically equivalent

Protons HA & HB have different chemical shifts

Each has different coupling constant with HC

Constant JAC is a cis coupling constant

Constant JBC is a trans coupling constant

Therefore, HA & HB are not magnetically equivalent

They do not act as group to split proton HC

HB splits HC with constant JBC into a doublet

HA splits each component of doublet into doublets with coupling constant JAC

C = CHB

HA HC

X

Vinyl Compound

NMR Proton (1H) NMR Spectrum and Splitting Analysis of Vinyl

Acetate

04/19/23 66

Ha & Hb chemically equivalent, but not magnetically equivalent.

Each has different chemical shift.

Each has different coupling constantwith Hc.

Hb splits Hc into doublet (Jbc).

Ha then splits each Jbc doublet into a doublet.Similary, Ha splits Hc into doublet (Jac).

Hb then splits each Jac doublet into a doublet.Hc splits Ha & Hb into doublets.

Ha & Hb each then split these doublets.

NMR Aromatic Compounds (Substituted Benzene Rings)

We have previously stated that a magnetic field applied to an Aromatic ring becomes non-uniform (anisotropic) by the stabilizing effect of the Benzene Ring Current resulting in the protons being deshielded (electron density becomes less); thus, increasing the chemical shift. i.e., the absorption signal (Resonance Frequency) moves to the left on the chart – in the vicinity of 7.0 ppm.

Depending on the number and type of groups substituted on an Aromatic ring, the NMR spectra of the remaining protons on the ring are often complex, with the Chemical Shift moving up field or downfield.

04/19/23 67

NMR Some groups, such as – Cyano, Nitro, Carboxyl,

Carbonyl – are electron-withdrawing (deactivate the ring), decreasing the electron density, and resulting in an increase in the Chemical Shift, i.e., resonance frequency moves further down field.

For Electron-Withdrawing groups the Ortho & Para protons lose more electron density that the Meta protons; thus, are less shielded moving (increasing) the chemical shift downfield relative to the Meta protons.

04/19/23 68

NMR Aromatic Compounds (Substituted Benzene Rings) (Con’t)

Electron-donating groups such as – Methyl, Methoxy, Amino, Hydroxy – activate the ring and increase the electron density resulting in a decrease in the Chemical Shift, i.e., resonance frequency moves up field to the right.

For Electron–Donating groups, the Ortho & Para protons gain more electron density than the Meta protons; thus are more shielded moving (decreasing) the chemical shift up field slightly from the Meta protons.

Mono – Substituted Aromatic Rings

When a single substituted group is neither strongly electron-withdrawing (deactivates ring by decreasing electron density about the ring protons) nor strongly electron-donating (activates ring by increasing the electron density) – Methyl & Alkyl groups – , all ring protons (ortho, meta, para) have near identical chemical shifts resulting in a slightly broad singlet (the protons are not quite chemically equivalent).

See pattern “A” on slide 7304/19/23 69

NMR Aromatic Compounds (Substituted Benzene Rings) (Con’t)

Mono – Substituted Aromatic Rings (Con’t) In general, electron withdrawing groups (Cyano, Nitro,

Carboxyl, Carbonyl) decrease the electron density of the Ortho & Para protons more so than the Meta protons, resulting in the signal for the O & P protons being slightly more downfield than the Signal for the Meta protons as seen in pattern “C” on slide 73).

In the case of electron withdrawing groups with double bonds such as Nitro (NO2) and Carbonyl (C=O) groups, or other double bonds attached directly to the ring, Magnetic Anisotropy causes the Ortho protons to be much more deshielded than the Para & Meta protons, resulting in the Ortho protons having a significantly increased Chemical shift as seen in pattern “D” on slide 73.

In the case of electron donating group such as Methyl, Methoxy, Amino, Hydroxy, the Chemical Shift of the Ortho & Para protons, while not exactly the same, will be distinctly up field from the Meta protons as seen in pattern “B” on slide 73.04/19/23 70

NMR Aromatic Compounds (Substituted Benzene Rings) Con’t)

Mono – Substituted Aromatic Rings (Con’t)

For Monosubstituted Electronegative elements, such as Halides, which are electron withdrawing due to the Dipole effect, the electron withdrawing effect is less dominant than the electron donating resonance effect.

Thus, the increased electron density about the Ortho & Para protons would be increased relative to the Meta protons, resulting in an decrease in the Chemical Shift – signal moves up field as seen in pattern “E” on slide 64.

Note: The “m/p” signal is actually an overlapping of the “m” and “p” signals with the “p” signal slightly up field from the “m” signal.

The “o” proton has more electron density than the “p” proton because of the Magnetic Anisotropy effects of the ring current.

04/19/23 71

NMR Aromatic Compounds (Substituted Benzene Rings) Con’t)

Para – Disubstituted Rings

P-Disubstituted patterns are generally easy to recognize.

When the Aromatic ring has two groups substituted in the para position, three distinct patterns are possible, depending on the relative electronegativity of the two groups.

If the two p-substituted groups are identical, the four remaining protons on the ring are chemically and magnetically equivalent producing a singlet as seen in pattern “F (a)” on slide 73.

If the two p-substituted groups are different, the protons on one side of the symmetrically ring split the protons on the other side of the ring into a doublet.

The patterns produced by the two doublets will be different depending on the relative electronegativity of the two substituted groups as seen in patterns F (b) & F (c) on slide 73.

04/19/23 72

NMR Common Aromatic Patterns

04/19/23 73

NMR “Activating” and “Deactivating” groups and the impact of

the changing electron density in the Benzene ring on Chemical Shift of ortho, meta, para protons

04/19/23 74

Methoxyl (0-CH3) group is Electron Donating, activates ring by adding electron density to o/p protons.

Chemical Shifts, , of ring o/p protons are moved up field, i.e., decreasing ppm because of increase electron density.

Note location of “Methyl Protons” absorption at 3.7 ppm (without influence of “O” it would be around1 ppm).

m o, p

m

m

p o

o

3 Methyl Protons

Anisole (C7H8O)



04/19/23 75

m o/p

The Amino group is Electron Donatingand Activates the ring.

Increases electron density aroundOrtho & Para protons relative to Meta.

Chemical Shift, , of ring protons is up field, decreased ppm

o

m

m

op

2 AminoProtons

Aniline (C6H7N)



04/19/23 76

Nitro group is electron withdrawing and deactivates the ring.

Protons in ring are deshielded movingChemical Shift downfield.

Magnetic Anisotropy causes the Ortho protons to be more deshielded than the Para & Meta protons.

p m

o

om

mp

o

Nitrobenzene (C6H5NO2)



04/19/23 77

Ha Ha’

Hb Hb’

Ha&Ha’Hb&Hb’

2 Amino Protons

The Molecular Ion peakfrom Mass Spectrometry would have indicated the presence of the single Chlorine atom and Nitrogen.

Para Di-Substituted Benzene ring Ha & Ha’ have same Chemical Shift Hb & Hb’ have same Chemical Shift Ha is split into doublet by Hb Hb is split into doublet by Ha Two sets of peaks produced by relative

electronegativity of Amino & Cl groups

P-Chloroaniline (C6H6ClN)



04/19/23 78

c

b a

The Methoxy group is moderately activating, while the Nitro groups are strongly deactivating (electron withdrawing)

Net effect is to Decrease the electron density about the ring protons

The a & b protons are Ortho to the strongly deactivating Nitro groups, thus, they have reduced electron density and their Chemical Shift is down field relative to the “c” proton

All protons interact to produce Spin-Spin Coupling.

a b c

3H

2,4-Dinitroanisole (C7H6N2O5)

NMR Protons attached to atoms other than carbon

atoms Widely variable ranges of absorptions. Protons on heteroelements, such as oxygen

(hydroxyl, carboxyl, enols), and nitrogen (amines, amides) normally do not couple with protons on adjacent carbon atoms to give spin- spin splitting.

Solvent effect - The absorption position is variable because these groups undergo varying degrees of hydrogen bonding in solutions of different concentrations.

Amount of hydrogen bonding can radically affect the valence electron density producing large changes in chemical shift.

04/19/23 79

NMR Protons attached to atoms other than carbon

atoms (Con’t) Absorption signals are frequently broad relative

to other singlets, which can be used to help identify the signal.

Protons attached to Nitrogen atoms often show extremely broad signals and can be indistinguishable from the base line.

04/19/23 80

Typical Ranges for Groups with Variable Chemical Shifts

NMR NMR Spectra at Higher Field Strengths

The 60 MHz spectrum for some compounds can be very difficult to read because the chemical shifts of several groups of protons are very similar and they overlap.

Chemical shifts are dependent on the frequency of the applied radiation (or the strength of the applied magnetic field).

Note: Coupling Constants (J) ARE independent.

As the field strength increases, the chemical shifts of proton groups in also increase.

04/19/23 81

NMR NMR Spectra at Higher Field Strengths (Con’t)

For example, a proton group resonating at 60 Hz in a60 Mhz instrument would resonate at 100 Hz in the 100 Mhz instrument.

This effectively stretches the X-axis scale improving resolution.

Note, however, the value in ppm, does not change.

04/19/23 82

NMR Chemical Shift Reagents

Interactions between molecules and solvents, such as those due to hydrogen bonding can cause large changes in resonance positions of certain types of protons, such as hydroxy (OH) and amino (NH2).

Changes in resonance positions can also be affected by changing from the usual NMR solvents, such as chloroform (CCL4) and deuterochloroform (CDCl3) to solvents like benzene which impose local anisotropic effects on the surrounding molecules.

In some cases a solvent change allows partially overlapping multiplets to be resolved.

Most chemical shift reagents are organic complexes of the Lanthanide elements.

04/19/23 83

NMR Chemical Shift Reagents (Con’t)

When added to a compound, these complexes produce profound chemical shifts, sometimes up field and sometimes downfield, depending on the metal.

Europium, erbium, thulium, and ytterbium shift resonances to the lower field (higher ).

Cerium, praseodymium, neodymium, samarium, terbium, and holmium shift resonances to the higher field (lower ).

Another advantage of shift reagents is that shifts similar to those observed at higher fields can be induced without the need to purchase an expensive higher field instrument.

The amount of the shift change depends on the distance separating the lanthanide element from the proton group and the concentration of the shift reagent.

04/19/23 84

NMR Example 1H1 NMR Spectra

04/19/23 85

Suggestions

For

Interpreting NMR Spectra

NMR Example Spectra NMR Spectra Interpretation Procedure

The following 4 slides provide a suggested process to follow in attempting to interpret an NMR Spectra.

The 1st slide is a typical NMR spectra showing 5 signals each consisting of one or more peaks.

Note that each signal has a number associated with it representing the area integration, i.e., the number of protons generating the signal.

Also note the expanded spectra of the signal at 2.6 ppm. Expanded spectra are often provided when the signal lacks sufficient resolution to clearly display the number of peaks being generated by the protons on the carbon atom generating the signal.

04/19/23 86

NMR Example Spectra The 2nd slide presents interpretations of each

signal relative to the number of protons (n) on the carbon atom generating the signal and the number of protons attached to adjacent carbons atoms that produce the n+1 peaks comprising the signal as a result of “spin-spin” splitting.

The 3rd slide shows how the fragments from slide 2 might fit together.

The 4th slide ties it all together.

04/19/23 87

NMR Example Spectra Four slides demonstrating a process for

interpreting an NMR Spectra

04/19/23 88

3H

Chemical Shift () in PPM

Note: Magnetic Field (Ho) increases

Slide 1

NMR Example Spectra

04/19/23 89

Sextet

Quintet

2 protons see 4 protons 5 peaks (quintet) produced

3 protons see 2 protons 3 peaks (triplet) produced

1 proton sees 5 protons 6 peaks (sextet) produced

3 protons see 1 proton 2 peaks (doublet) produced

3H

Mono-substitutedBenzene Ring

Doublet TripletFrom chemical shifts, peak integration values, and splitting patterns, develop substructures for each signal.

NMR Example Spectra

04/19/23 90

Solve the Puzzle

NMR Example Spectra

04/19/23 91

The Solution: 2-Phenylbutane (C10H14)

3H

Integration value (Area under signal)is proportional to No. of Protons

generating the signal

3 + 2 +1 = 6

Spin-Spin SplittingNo. of peaks in a signal is equal to the number of protons on alladjacent carbon atoms plus 1 (N+1 rule)

5 protons on amono-substituted

Benzene Ring

3 protons on aMethyl group

see 2 adjacentprotons

2 protons on aMethylene group

see 4 adjacenprotons

sextet

quintet

doublet

1 proton onMethine groupsees 5 adjacen

protons

3 protons on aMethyl group

see 1 adjacentproton

triplet

NMR Example Spectra

04/19/23 92

Benzyl Acetate (C9H10O2)

Methyl Protons (3)No adjacent protons;no splitting

Methylene Protons (2)No adjacent protons;no splitting

Aromatic Protons (5)

NMR Example SpectraCyclohexene (C6H10)

04/19/23 93

c

c´

b´

b

a

a´c

b

a

3 different chemical environments

Peaks actually show splitting,but is hard to see at this resolution (90Hz)

n+1=2+1=3(triplet)

n+1=3+1=4(quartet)

2H

4H

4H

The single protons on the “c” carbons are equivalent; thus, they do not split each other.The single protons on each “c” carbon split the respective adjacent “b” proton to form two equal overlapping triplets

The “a” protons have a smaller Chemical Shift than the “b” protons because of their relative position to theelectron rich bond.

The sets of 2 protons on each of the adjacent “a” carbons are equivalent and do not split each other.

Each 2 proton set on an “a” carbons splits its respective adjacent 2 “b” protons to form 2 overlapping triplets.

The 2 protons on each of the equivalent “b” carbons split their respective adjacent “protons (1 on the “c” carbon and 2 on the “a” carbon) to form two equal overlapping quartets

n+1=2+1=3(triplet)

NMR Example Spectra2,5-Hexanedione (Acetonylacetone) (C6H10O2)

04/19/23 94

n+1=0+1=1(singlet)

n+1=0+1=1(singlet)

2 Sets Methylene ProtonsChemical & Magnetically Equivalent

They do not split each other

6H

4H

NMR Example Spectra Cis-Stilbene (C14H12)

04/19/23 95

Aromatic Protons (10)(very fine splitting)

Vinyl Protons (2)Chemically & Magnetically Equivalent

Do Not Split

NMR Example SpectraMethyl Phenyl Acetate (C9H10O2)

04/19/23 96

Aromatic Protons (5)

Methylene Protons (2)n+1 = 0 + 1 =1

Chem Shift – 3.65 ppm

Methyl Protons (3)n+1 = 0 + 1 = 1

Chem Shift – 3.60 ppm

Note: 2 Overlapping Absorptions!! Electronegative Carboxyl Oxygen forces shiftof Methyl Proton absorptions downfield to about same location as shift of MethyleneProtons forced downfield byeffects of electronegative Carbonyl group.

NMR Example Spectra4-Heptanone (C7H14O)

04/19/23 97

n+1 = 2+1=3 n+1 = 5+1=6 n+1 = 2+1=3

The Methyl & Methylene groupprotons on the left side of theMolecule are Chemically & MagneticallyEquivalent to their counterparts on theright side, thus, the Chemical Shifts arethe same and signals overlap

NMR Example SpectraIsopropyl Benzene (C9H12)

04/19/23 98

6H

1H

5H

1 proton sees6 protons

Producing Septetn+1=6+1=7

6 protons see1 proton

producingDoublet

n+1=1+1=2

NMR Example SpectraP-Nitrotoluene (C7H7NO2)

04/19/23 99

3H

Nitro group is strongly deactivating andthe Methyl group is weakly activating.The net withdrawing effect on benzene ringmoves the chemical shift downfield, theProtons ortho to the Nitro group more so thanThe protons ortho to the Methyl group.

P- Dibsubstitution

4H

NMR Example SpectraPhenacetin (C10H13NO2)

04/19/23 100

n+1=0+1=1(singlet)

n+1=3+1=4(quartet)

2H

1H

3H

P-Disubstitution

n+1=2+1=3(triplet)

3H

4H

NMR Example SpectraIsobutyric Acid (C4H8O2)

04/19/23 101

n+1=1+1= 2(doublet)

n+1=6+1=7(septet)

CarboxylicProton

6H

1H1H

NMR Example Spectra4-Amino-Acetophenone (C8H9NO)

04/19/23 102

2 2

2

3

P-Disubstitution

3 Methyl protons see0 adjacent protonsproducing singlet

n+1=0+1=1

Chemical Shift moveddownfield because

of proximity toElectronegative

Carbonyl group (C=O)

Withdrawing Donating

NMR Example SpectraButyrophenone (C10H12O)

The Chemical Shift of the Methylene group nearest the moderately deactivating Carbonyl group is greater than the adjacent Methylene group, because the deactivating effect diminishes with distance

04/19/23 103

3

2

Propoxyl group is moderatelydeactivating, deshielding “o” ring protons more so than “p” protons (aniostropic effect)

“m” protons are deshielded least

2

ortho(2)

para, meta(3)

NMR Example SpectraCyclohexanone (C6H10O)

04/19/23 104

4

4

2The 2 (c) protons see the 4 (b) protons producing a 4 + 1 = 5 quintet

The 4 (a) protons, probably 2 identical Methylene groups each of which is attached to a (b) Carbon with 2 protons.The net effect of these equivalent structures is that two protons see two adjacent protons producing a triplet: 2+1 = 3.

The 4 (b) protons represent 2 identical Methylene groups each of which is attached to an equivalent Methylene group.The (b) protons also see the two (c) protons.The net effect of this is that the 4 (b) protons see effectively 2 (a) protons and 2 (c) protons producing a 4 +1 = 5 quintet.

Two quintetsoverlappiing

a a

bb

c

NMR Example SpectraIsobutyl Acetate (C6H12O2)

04/19/23 105

6

2

2

3

Nonet DoubletTriplet

Singlet

1 proton sees 8 adjacent protons

producing (8+1) 9 peaks3 protons see 0 protons on

Carbonyl carbon producing a singlet

6 protons see1 adjacent protonproducing doublet

2 protons see1 adjacent protonproduces doublet

NMR (Carbon–13) Carbon-13 Nuclear Magnetic Resonance

Carbon-13 (13C6) possesses spin (I=1/2); thus it is a candidate for NMR

Carbon-13 resonances are not easy to observe: Natural abundance of of C-13 is 1.08 % Magnetic Moment () is low Resonances are 6000 times weaker than those of

hydrogen Fourier Transform instrumental techniques make it

possible to observe 13C6 nuclear magnetic resonance. Chemical Shift is most useful parameter derived from

13C6 spectra. Integrals (signal areas) are Unreliable and not

necessarily related to the relative number of 13C6 atoms present.

Hydrogens attached to 13C6 atoms cause spin-spin splitting, spin-spin interaction between adjacent carbon atoms is rare.

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NMR (Carbon–13) Carbon-13 Nuclear Magnetic Resonance

The Chemical Shifts for 13C6 spectra are reported by the number of ppm ( units) that the signal is shifted downfield from TMS, just as in the proton NMR.

The 13C6 scale ranges from 0 (TMS) in the upper (higher magnetic)_field to 225 ppm in the lower field.

Resonance signals are more distinct providing more resolution.

Adjacent CH2 carbons have distinct resonance signals.

Unusual to find two carbon atoms in a molecule with the same chemical shift unless they are chemically equivalent by symmetry.

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NMR (Carbon–13) Coupled C-13 Spectra

In coupled C-13 NMR spectra, the spectra diagram exhibits spin-spin splitting, similar to Proton NMR, but with a significant difference

The splitting pattern exhibited by a particular C-13 atom follows the N+1 rule, but the value of N is based on the number of protons attached to the C-13 atom, NOT the number of protons attached to the adjacent carbon atoms.

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NMR (Carbon–13) Coupled C-13 Spectra - Example

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A. In the coupled spectra of Ethyl Phenyl Acetate (Slide 107),the Methyl group at 14.2 ppm is split into quartet by the three hydrogen atoms attached to the carbon itself, not the protons on the adjacent Methylene (CH2) group

B. Each quartet line is split into a triplet by the adjacent CH2 group (not seen on chart).

Ethyl Phenyl Acetate

Carbons1 AromaticAr

1 Benzyl CH2

1 Methylene

CH2

1 Methyl CH3

1 CarboxylO=C-O

(See Slide 113)

CH2 C O CH2 CH3

O

NMR (Carbon–13) Coupled C-13 Spectra - Example (Con’t)

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C. Two CH2 groups

The Methylene (CH2) group with the Ethyl group (60.6 ppm) is deshielded by the adjacent O and forms a triplet because of the two attached hydrogens

The Benzyl (CH2) group at 41.4 ppm is also a triplet

D. The carbonyl appears to be a singlet at 171.1, but it is actually a triplet because of the adjacent -CH2 group (very fine, not easy to see).

E. The aromatic ring carbons have resonances over the range of 127-136 ppm.


Carbons1 AromaticAr

1 Benzyl CH2

1 Methylene

CH2

1 Methyl CH3

1 CarboxylO=C-O

(See Slide 113)

CH2 C O CH2 CH3

O

NMR (Carbon–13) Broad-Band Decoupled 13C6 Spectra

Simple molecules such a Ethyl Phenyl Acetate can yield interesting and useful structural information, namely the number of hydrogens attached to each carbon.

However, for larger molecules the spectra can become very complex with overlapping splitting patterns.

A broader range of 13C6 spectra can be obtained if all the protons are decoupled from the molecule by irradiating them simultaneously with a broad spectrum of frequencies in the appropriate range.

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NMR (Carbon–13) Broad-Band Decoupled 13C6 Spectra (Con’t)

The decoupled spectra are much simpler and easier to interpret.

Each signal represents a different carbon atom.

If two carbon atoms are represent by a single signal, they must be equivalent by symmetry.

In the Aromatic ring of Ethyl Phenyl Acetate, the carbons at positions 2 & 6 produce a single signal, and the carbons at positions 3 & 5 also produce a single signal.

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NMR (Carbon–13) Carbon-13 Spectra for coupled and decoupled


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NMR (Carbon–13) Chemical Shifts for Carbon-13 NMR

Chemical Shift of each Carbon indicates its type and structural environment.

As with proton NMR, electronegativity, hybridization, and anisotropy effects influence the chemical shift.

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Correlation Chart for Carbon-13 (ppm from TMS)

NMR (Carbon–13) Carbon-13 Spectra (Proton Decoupled)

2,2-Dimethylbutane

Six carbon atoms, but only 4 signals + solvent signals for CDCl3 and TMS.

Single Methyl Carbon (a), signal at 8.8 ppm.

Three Methyl Carbons (b) on quaternary Carbon (c), signal at 28.9 ppm.

Quaternary Carbon (c), which has no hydrogens attached, appears as a small (weak) signal at 30.4 ppm.

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Con’t on next slide

NMR (Carbon–13) Carbon-13 Spectra (Proton Decoupled)

2,2-Dimethylbutane (Con’t)

Methylene Carbon (d), signal at 36.5 ppm.

Relative size of signals gives some idea of number of each type of carbon Note: Signal at 28.9 ppm for 3 carbon atoms.

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2,2-Dimethylbutane

NMR (Carbon–13) Aromatic Ring Methyl Substitution

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5 Carbon Types 3 Carbon Types 9 Carbon Types 6 Carbon Types

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

NMR (Carbon–13) Bromocyclohexane & Cyclohexanol

A carbon atom should be deshielded by the presence of an electronegative element.

The ring carbon atoms will resonate at a higher field (smaller shift) as they are located farther away from the electronegative element

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Bromocyclohexane

Cyclohexanol

NMR (Carbon–13) Cyclohexene

Diamagnetic Anisotropy - Carbon atom attached to the double bond (c) is deshielded by the effects of the non-uniform magnetic field produced by the presence of the electrons.

Carbon atoms located farther from the double bond resonate at higher field (less chemical shift).

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Cyclohexene

Chemical Shift

(c) > (b) > (a)

NMR (Carbon–13) Toluene (Hydrogen Coupled Spectrum)

Diamagnetic Anisotropy causes the carbon atom signals of the aromatic ring [ (e) > (d) > (c) > (b) ] to appear at lower field strengths (higher values).

The signal (a) for the Methyl carbon atom attached to the ring located in the higher field ( value about 22) illustrates little anisotropic effect of aromatic ring.

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Toluenea

NMR (Carbon–13) Cyclohexanone

Strong deshielding effect of carbonyl group.

The carbonyl carbon atom (d) resonates at a very low field value – value about 211.3

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NMR (Carbon–13) Symmetry - 1,2- & 1,3-Dichlorobenzene isomers

A plane of symmetry for 1,2-Dichlorobenzene defines three (3) different Carbon atoms, producing three signals.

A plane of symmetry for 1,3-Dichlorobenzene defines four (4) different Carbon atoms, producing four signals

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1,2-Dichlorobenzene

1,3-Dichlorobenzene

NMR Summary NMR Summary Notes

NMR - An instrumental technique to determine the number, type, and relative positions of certain atoms in a molecule.

The technique is based on the nuclear spin properties of the nuclei of certain elements and isotopes.

When the nuclei of these elements are placed in a strong magnetic field and irradiated with low energy radio waves (wavelengths of 1 - 5 meters) they absorb energy through a process called magnetic resonance.

Under these conditions the absorption of energy is quantized producing a characteristic spectrum for the compound.

The absorption of energy does not occur unless the strength of the magnetic field and the frequency of the electromagnetic radiation are at specific values.

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NMR Summary NMR Summary Notes (Con’t)

1H1 and 13C6 have odd atomic number and/or atomic mass; thus they have spin properties and are the two primary isotopes utilized in NMR.

1H1 and 13C6 have two spins states (+1/2 & -1/2).

Nuclei with +1/2 spin state align with an applied magnetic field.

Nuclei with -1/2 spin state oppose magnetic field. Resonance - If radiofrequency (low energy, long

wavelength) waves are applied to nuclei with spin in an applied magnetic field, the lower energy nuclei aligned with the field absorb a quantized amount of energy, reverse direction, and become opposed to the field.

The stronger the magnetic field, the greater the energy absorption (resonance).

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An NMR instrument applies a constant radiofrequency of 60, 100, or 300 MHz and applies an increasing magnetic field strength.

A higher field strength instrument allows for cleaner separation of overlapping signals, i.e., more resolution.

Protons or Carbon-13 atoms of different types (chemical environments electronegativity, anisotropy, etc.) resonate at unique field strengths measured in Hertz (cycles per second) producing a signal (peak) on the chart paper.

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A parameter called the “Chemical Shift ()” has been defined to give the position of the absorption of a proton a quantitative value.

The Chemical Shift values are report in units of “Parts Per Million” (ppm).

Magnetic field, in Hertz, increases from left to right on chart scale, while increases from right to left starting with 0 (for TMS) to 13.

Protons in molecules in chemically equivalent environments will generally have the same chemical shift - one signal is produced.

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Observed Shift from TMS (in Hz) HzChemical Shift () = = = PPM 60 MHz MHz


The area under an NMR signal is proportional to the number of protons generating the signal.

The NMR Spectrometer electronically integrates the area under the signal.

The height the of traced vertical line gives the relative numbers of each type of hydrogen.

Diamagnetic Shielding - Valence electrons shield proton from applied magnetic field.

Electronegative elements produce an electron withdrawing effect, deshielding the proton, resulting in a larger chemical shift, that is, a smaller magnetic field is required to induce resonance.

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The movement of the electrons in aromatic rings (benzene, etc), alkenes C=, Alkynes (C), and aldehydes (O=CH) produce their own magnetic fields causing the applied magnetic field to become non-uniform (diamagnetic anisotropy), which deshields the proton increasing the chemical shift.

In some cases, such as acetylenes, the effect of the anisotropic field is to shield the hydrogens, decreasing the chemical shift.

Protons are affected by the presence of protons on nearby, generally adjacent, carbon atoms.

Each type of proton “senses” the number of equivalent protons (n) on the carbon atom next to the one it is bonded, and splits its resonance signal into n+1 signals, a multiplet – Spin – Spin Splitting.04/19/23 128


Coupling Constant (J) - The spacing, in Hz, between the component signals in multiplet.

The Coupling Constant has different magnitudes for different types of protons.

Protons that have the same chemical shift and are coupled equivalently to all other protons are magnetically equivalent and do not show spin-spin splitting.For example: Protons attached to the same carbon atom that have the same chemical shift do not split each other.

In monosubstituted aromatic rings, all ring protons have near identical chemical shifts resulting in a single, but slightly broader single.

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Electron-withdrawing (electronegative) groups, such as nitro, cyan, carboxyl, and carbonyl, deshield the ring moving the chemical shift downfield (increase ).

Electron-donating groups, such as methoxy, amino, increase the electron density, moving the chemical shift up field (decrease ).

Hydrogen on heteroelements - Protons on elements other than carbon, such as, oxygen (hydroxyl, carboxyl, enols), nitrogen (amines, amides) do not couple with protons on adjacent carbon atoms; thus no spin-spin splitting.

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Solvent effect - The absorption position in variable because these groups undergo varying degrees of hydrogen bonding in solutions of different concentrations.

The amount of hydrogen bonding can radically affect the valence electron density producing large changes in chemical shift.

Chemical Shift Reagents - Chloroform, Deuterochloroform, Organic Complexes of Lanthanide Elements.

When added to the compound in question, these complexes produce profound chemical shifts, sometimes up field and sometimes downfield, depending on the metal.

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Europium, erbium, thulium, and ytterbium shift resonances to the lower field (higher ).

Cerium, praseodymium, neodymium, samarium, terbium, and holmium shift resonances to the higher field (lower ).

Carbon-13 NMR - 13C6 has spin and produces NMR spectra.

Carbon-13 resonances not easy to observe - natural abundance 1.08 %, low magnetic moment, 6000 times weaker than those of hydrogen.

Integrals (signal areas) are not reliable as indicators of the number of carbon atoms.

Chemical shift scale - 0 to 200 (higher resolution).

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Higher resolution produces more distinctive signals making it easier to resolve signal overlapping.

Unusual to find two carbon atoms with same chemical shift unless chemically equivalent.

Except for a few simple molecules, 13C6 spectra can become very complex, making interpretation difficult.

Irradiation of the molecules simultaneously with a broad spectrum of frequencies decouples the hydrogens from the molecule producing a much simpler spectra.

Electronegativity, hybridization, and anisotropy effects influence the chemical shiftt

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