Nmr Lecture

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Organic ChemistryLaboratoryBuilding A Toolset

For

The Identification of Organic Compounds

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Physical Properties

Melting Point

Boiling PointDensity

Solubility

Refractive Index

Chemical Tests

Hydrocarbons

AlkanesAlkenes

Alkynes

Halides

Alcohols

AldehydesKetones

Spectroscopy

Mass

(Molecular Weight)Ultraviolet

(Conjugation, Carbonyl)

Infrared

Functional Groups

NMR(Number, Type, Location

of protons)

Gas Chromatography

(Identity, Mole %)


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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

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The Electromagnetic Spectrum

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MicrowaveInfraredX-RayVacuum

UV

VisibleNear

Ultraviolet

Vibrational

Infrared

Nuclear

MagneticResonance

Radio Frequency

400 nm200 nm 800 nm 2.5 15

1 m 5 m

Blue Red

Cosmic

&

Ray

0.01 nm

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

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 107Hz

3 x 108Hz

1.5 x 1015Hz 1 x 109Hz3 x 1011Hz

1.2 x 1014HzFrequency

Wave Number

Wavelength


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NMR

Nuclear Magnetic Resonance Spectroscopy

NMR

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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 Splitting11/10/2014

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NMR NMR

NMR is an instrumental technique to determine the

number, type, and relative positions of certain Nuclei in amolecule

NMR is concerned with the magnetic properties of thesenuclei

Many Nuclei types can be studied by NMR, but the twomost 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 - Resonance11/10/2014

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NMR The Magnetic Properties

Many atomic nuclei have a property called Spin

Since all nuclei have a charge (from the protons in thenucleus), a spinning nuclei behaves as if it were a tinymagnet, generating its own Magnetic field

The Magnetic Field of such nuclei has the followingpropertiesMagnetic Dipole, Magnetic Moment andQuantized Spin Angular Momentum

The Magnetic Moment ()of a nuclei is a function of itsCharge and Spin and is defined as the product of the polestrength and the distance between the poles

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

Note: Nuclei with a Mass & Atomic number combination ofEven/Even do not have Spin and are not useful for

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NMR Nuclear Spin States

Nuclei with spin (Magnetic Moment, Quantized Spin

Angular Momentum, Magnetic Dipole) have a certainnumber of Spin States.

The number of Spin States a nuclei can have isdetermined by its Spin Quantum Number I, a physicalconstant, 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 ofthe 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) Spin11/10/2014

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NMR Nuclear Spin States (Cont)

The number of allowed Spin States for a nuclei is:2I + 1

with 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, -5/2 The 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 a

Proton (1H1) or a Carbon-13 (13C6) nuclei is:

[2 * + 1 = 1 + 1 = 2]

Therefore, the two spins states for either nuclei are:

1/2 & - 1/211/10/2014

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NMR Nuclear Spin States (Cont)

In the absence of an applied Magnetic field, all the spinstates of a given nuclei are of equivalent energy(degenerate), equally populated, and the spin vectorsare randomly oriented

When an external Magnetic Field is applied, the

degenerate spin states are split into two opposing statesof unequal energy

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

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

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

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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 +1/2

Aligned

Spin -1/2

Opposed

-1/2 Opposed to Field

+1/2 Aligned with Field

E

No

Field

Externally Applied

Magnetic 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


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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-13atoms, begin to Precess about the axis of spin with AngularFrequency , 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 60MHz

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

The stronger the applied magnetic field, the higher theFrequency of Precession and the greater energy difference

between the +1/2 and -1/2 spin states11/10/2014

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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 sothat the externally applied magnetic field strength is held

constant while a RF oscillator subjects the sample to thefull 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 externallyapplied magnetic field strength is changed.

Most NMR instruments today are of the Continuous Wavetype

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NMRTypically, Continuous Wave (CV) Spectrometers are used inwhich the externally applied magnetic field is held constant

and RF Radio Oscillator applies a full range of frequenciesat 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 strongexternally 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 transferredfrom 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 isreferred 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.11/10/2014

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NMR Electron Density, Frequency of Angular Precession

Protons exist in a variety of chemical and magnetic

environments, each represented by a unique electrondensity configuration.

Under the influence of a strong externally appliedmagnetic field, the electrons around the proton are

induced to circulate, generating a secondary magneticfield (local diamagnetic current), which acts inopposition (diamagnetically)to the applied magneticfield.

This secondary field shields the proton (diamagneticshielding or diamagnetic anisotropy)from the influenceof the applied magnetic field.

Recall from slide # 13 that the Angular Frequency ofPrecession is directly proportional to the applied

Magnetic Field strength.11/10/2014

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NMR Electron Density, Frequency of Angular Precession (Cont)

As the shielding of the proton increases (increased

electron density)it diminishesthe net applied magneticfield strength reaching the proton; thus the AngularFrequency of Precession is lower

If the electron density decreases, more of the applied

magnetic field strength impacts the proton and it willprecess at a higher Angular Frequency

Thus, each proton with a unique electron densityconfiguration willResonateat a unique Frequency ofAngular Precession

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

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NMR NMR SpectraFourier Transform vs. Continuous Wave

Fourier Transform

In a Fourier Transform (FT) NMR, the spectrumproduced is a plot of the magnetic field strengthrepresenting the frequency of the resonance signalon the X-axisversus the intensity of the

absorption on the Y-Axis.

Each signalconsisting of one or more peaksrepresents the Resonance Frequency of aparticular type of proton with a unique chemical &

magnetic (electron density) environment.

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Fourier Transform (Cont)

As the pen of the recorder moves from left to right,the value recorded on X-axis of the NMR spectrumrepresents small increments of increasing magneticfield strength.

The right side of the NMR Spectrum is referred toas being Upfield (higher magnetic field strength).

The left side of the NMR Spectrum is referred to asbeing Downfield (lower magnetic field strength).

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(Cont)

Continuous Wave

In a Continuous Wave NMR, the spectrum producedis a plot of the RF Radio Oscillator Frequencyversus the intensity of the absorption on the Y-Axis.

As before, each signalconsisting of one or morepeaksrepresents the Resonance Frequency of aparticular 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 spectrumrepresents a decreasing RF Oscillator Frequency(Resonance Frequency)

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(Cont)

Continuous Wave (Cont)

The Signals on the right side of the NMR Spectrumrepresent protons (C-13 nuclei) that Resonate atlower frequencies.

The Signals on the left side of the NMR Spectrumrepresent protons (C-13 nuclei) that Resonate athigher frequencies.

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NMR NMR SpectraFT 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 representthose protons (or C-13 nuclei) that resonate at the highestexternally applied magnetic field strength and the lowestfrequency.

This statement would appear to be in conflict with thestatement 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 theinfluence of the secondary magnetic field set up by theDiamagnetic Current from circulating valence electrons.

This magnetic field opposes the externally applied fieldreducing the effect of the applied Magnetic Field on the

proton, which in turn lowers the Resonance Frequency11/10/2014

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NMR NMR SpectraFT or CW: the spectrum looks the same (Cont)

The protons that resonate and produce signals on the right

side of the NMR Spectrum (up field) have higher electrondensity shields than protons that resonate downfield

The net effect of the difference between the externallyapplied magnetic field and the amount prevented from

actually reaching the proton results in a significantly reducedResonance Frequency

As the NMR spectrum moves from right to left, the electrondensity about the various proton environments isdecreasing, resulting in more of the externally appliedmagnetic field getting through to the proton

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

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NMR NMR SpectraBackground Summary

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In a continuous Wave NMR, thestrength of the externally applied

magnetic field is held constant.

Protons that produce signals on theright side of the NMR spectrumhave a higher amount of valenceelectron shielding.

The Magnetic Field produced by

circulating valence electrons(Diamagnetic Current) opposes theexternally applied Magnetic Field.

The Diamagnetic Field diminishesthe amount of Applied MagneticField reaching the proton.

The net amount of magnetic forceimpacting the proton is reducedresulting in a lower ResonanceFrequency.

As the Electron Density about aproton decreases downfield, theResonance Frequency increasesbecause more of the applied

Magnetic Field impacts the Proton.

Applied Magnetic Field StrengthHois held constant

Shielding of Proton by Valence Electrons

Diamagnetic (Anisotropic) Magnetic Field Strength

Produced by Circulation of Valence Electrons

Net Magnetic Field Impacting Proton

Frequency of Angular Precession

(Resonance Frequency)

Signal

TMS

PPM 013

Applied Radio Frequency - RF

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NMR NMR SpectraThe Chemical Shift

The differences in the applied Magnetic Field strength(Angular Frequency of Precession) at which thevarious proton configurations in a molecule Resonateare 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 ofresonance signals in the parts per million range.

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NMR NMR SpectraThe Chemical Shift

The typical technique is to measure the differencebetween the Resonance signals of various samplenuclei and the Resonance signal of a standardreference sample (see slides 25 & 26).

A parameter, called the Chemical Shift (), is

computed from the observed frequency shiftdifference (in Hz) of the sample and the standardresonance signal divided by the applied MagneticField rating of the NMR Spectrometer (in MHz).

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

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NMR NMR SpectraThe Chemical Shift (Cont)

The Chemical Shift is reported in units of:

Parts Per Million (ppm)

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Ex: If a proton resonance was shifted downfield 100 Hz relative tothe 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 013 In other words: Chemical Shift values decrease with increasing

Magnetic field strength or Chemical Shift values increase withincreasing Resonance frequency!

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

60 MHz MHz

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NMR NMR SpectraThe Internal Reference Standard

The universally accepted standard used in NMR is:

Tetramethylsilane (TMS)

The 12 protons on the four carbon atoms have the samechemical and magnetic environment and they resonate atthe same field strength, i.e., one signal (1 peak) isproduced

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

The strength of the Diamagnetic Field generated by thevalence electrons in TMS is greater than most otherorganic compounds

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Thus, little of the applied magnetic field gets through to

the TMS protons reducing the Frequency of AngularPrecession (Resonance Frequency) to a value that islower than most other organic compounds.

For most all other Proton environments, the electron

density is less than TMS and slightly more of the appliedmagnetic field gets through to the protons resulting in aslightly higher frequencies of Angular Precession.

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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> 0and will be downfieldfrom the TMS signal.

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NMR NMR SpectraSimple Example

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All six protons of Ethane are

chemically and magnetically

equivalent and all resonate at thesame 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 aphenomenon called spin-spin

splitting

NoteSee 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 groupprotons 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 electronicallyintegrated area under the signal curve and is proportional to thenumber of Protons generating the signal, i.e., Ethane has 6 chemicallyand magnetically equivalent protons

See slides 36-39 for a discussion of signal integration

Signal(singlet)

Chemical Shift (PPM)

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

Ethane TMS

(6)

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NMR NMRSimple Examples

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

The 3 Triplet peaks are produced by Spin-Spinsplitting based on the 2 protons attached tothe 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-spinsplitting based on the 6 protons attached tothe 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 on

Methyl Group Carbonattached to a Benzenering Carbon that has no

attached protons.

Therefore, the signal is asinglet with no splitting.

5 unsubstituted Protons

on Benzene ring are notequivalent, producingcomplex spitting

patterns typical of theresonance 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 donates

electrons to Benzene ringactivating it. The Methyl

protons have less electron

density (deshielded), thus,

the Chemical Shift is moved

downfield.

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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 differentchemical shifts, i.e. a signal is produced for each.

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

H H

H

H

H

H H

H

CH3

H

CH3

O

CH3 C O CH3

CH3 O CH2Cl

CH3 CH3

C

O

Cyclopentane

Acetone

Benzene Methyl Acetate 1,4 dimethyl benzene

(p-xylene)

1-Chloro Methyl Ether

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NMR An Isomer ExampleC5H12O

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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 theelectronegative 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 onspectrum variable.Note: All signals are singlets, i.e., no adjacent protons to produce spin-spine splitting.

3 2 0.9 0

tms

a

9

c

1

b

2

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.

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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

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2.1 ppm

(3 protons)3.6 ppm

(2 protons)

7.2 ppm

(5 protons)

Phenylacetone

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NMR NMR SpectrumPhenylacetone (103-79-7)

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C9H

10O

Methyl

3 Protons

Methylene

2 Protons

Ring

5 Protons

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NMR Integrals (Signal Area) (Cont)

NMR Spectrometer electronically integrates the area under a

signal and then traces rising vertical lines over each peak by anamount proportional to the area under the signalsee nextslide.

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

Integrals do not always correspond to the exact number ofprotons,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 wholenumbers.

See example computation on next Slide.

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NMR Integrals (Signal Area) (Cont)

NMR SpectrumBenzylacetate (C9H10O2)

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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)

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NMR Chemical ShiftImpact of Electronic Density

Valence Electrons

In the presence of the applied magnetic field, thevalence electrons in the vicinity of the proton areinduced to circulate (Local Diamagnetic Current)producing a small secondary magnetic field

The greater the electron density circulating about thenuclei, the greater the induced magnetic shieldingeffect

The induced magnetic field acts in opposition(diamagnetically opposed) to the applied magnetic

field, thus shielding the proton from the effects of theapplied field in a phenomenon called LocalDiamagnetic Shielding or Diamagnetic Anisotropy

As the Diamagnetic Anisotropy increases, the amountof the applied magnetic field reaching the proton is

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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) showanomalous 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 ingroups with electrons is dependent on theorientation of the molecule with respect to the appliedmagnetic field

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NMR Chemical Shift - Anisotropy (non-uniformity) (Cont)

The Diamagnetic Anisotropic effect diminishes with

distance

In most cases, the effect of the DiamagneticAnisotropic effect is to Deshield the protons,increasing the Chemical Shift

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

In a Benzene ring , the electrons are induced tocirculate around the ring by the applied magneticfield, creating a ring current, which in turn produces amagnetic field further influencing the shielding of thering protons

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NMR Chemical Shift - Anisotropy (non-uniformity) (Cont)

The presence of ring current causes the applied

magnetic field to become non-uniform (diamagneticanisotropy) in the vicinity of the benzene ring

The effect of the anisotropic field is to further deshieldthe benzene protons, increasingthe chemical shift

Thus, protons attached to the benzene ring areinfluenced 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 Ringprotons is to increase the Chemical Shift far downfield

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NMR Electron Density and Electronegativity

Protons in a molecule exist in many different electronicenvironments (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 configurationwill have a unique Angular Frequency of Precession

The electron density of a given proton and thus, thefrequency of precession, can be further influenced by

the presence of electronegativegroups in the vicinity ofthe proton

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

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NMR Chemical ShiftImpact 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 electrondensityabout the proton

Reducing electron density deshieldsthe proton from

the effect of the applied field, allowing more of the

magnetic field to impact the proton11/10/2014

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NMRChemical ShiftImpact of Electronegative Elements

(Cont)

Recall that Deshieldingthe proton increasestheResonance Frequency producing a greater chemicalshift, i.e., the resonance peak is moved downfield tothe left on the spectrum

The chemical shift increasesas the electronegativityof the attached element increases

Multiple substitutions have a stronger effect than asingle substitution

Electronegativity also affects the Chemical Shift ofProtons further down the chain. But the effect isdiminished as distance from the ElectronegativeElement increases

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NMR Chemical ShiftImpact of Electronegative Elements

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Compound CH3X CH3F CH3OH CH3Cl CH3Br CH3I CH4 (CH3)4SiElement X F O Cl Br I H Si

Electronegativity of X 4.0 3.5 3.1 2.8 2.5 2.1 1.8

Chemical 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.

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NMR

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Chemical Shift values of typical

Proton environments and the effects

of Electronegative Elements on the

Chemical Shift.

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

(ppm)

CHCl3

-OH, -NH

TMS

H

CH2FCH2Cl

CH2Br

CH2I

CH2O

CH2NO3

CH2ArCH2NR2

CH2S

C C H

CH2 C

O

CH2

C CH CC

C CH2 C

C CH3

Acids RCOOH 11.0 - 12.0 ppmAldehydes RCOH 9.0 - 10.0

Phenols ArOH 4.0 - 7.0

Alcohols ROH 0.5 - 5.0

Amines RNH2 0.5 - 5.0

Amides RCONH2 5.0 - 8.0

Enols 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 away

from 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.

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NMR General Regions of Chemical Shifts

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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

NMR


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NMRApproximate Chemical Shifts

Protons (1H1) Carbon (13C6)

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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)

1oAlkyl, RCH3 0.8 - 1.0

2o Alkyl, RCH2R 1.2 - 1.4

3oAlkyl, R3CH 1.4 - 1.7

Allylic, R2C C CH3 1.6 - 1.9

R

Ketone, RCCH3 2.1 - 2.6

O

Benzylic, ArCH2-R 2.2 - 2.5Acetylenic, RC CH 2.5 - 3.1

Alkyl Iodide, RCH2I 3.1 - 3.3

Ether, ROCH2R 3.3 - 3.9

Alcohol, HOCH2R 3.3 - 4.0

Alkyl Bromide, RCH2Br 3.4 - 3.6

Alkyl Chloride, RCH2Cl 3.6 - 3.8

Vinylic, RC2 CH

2 4.6 - 5.0

Vinylic, RC2 CH2-R 5.2 - 5.7

Aromatic, ArH 6.0 - 9.5

Aldehyde, RCH 9.0 - 10.0

O

Alcohol hydroxyl, ROH 0.5 - 6.0a

Amino, R NH2 1.0 - 5.0a

Phenolic, ArOH 4.5 - 7.7a

Carboxylic, RCOOH 11 - 12a

1oAlkyl, RCH3 0 - 402o Alkyl, RCH2R 10 - 50

3oAlkyl, RCHR2 15 - 50

Alkyl Halide or Amine, C-X 10 - 65

Alcohol or Ether, C-O 50 - 90

Alkyne, C 60 - 90

Alkene, C = 100 - 170

Aryl, Ar- 100 - 170

Nitriles, -C N - 120 - 130

O

Amides, -C - N - 150 - 180

O

Carboxylic Acids, Esters, C O 160 - 185

O

Aldehydes, Ketones, -C - 182 - 215

C-

NMR


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NMRFunctional Chemical Functional Chemical

Group Shift, ppm Group Shift, ppm

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TMS (CH3)4Si 0 AromaticARH 6.58.0Cyclopropane 0 - 1.0 ARCH (benzyl) 2.32.7Alkanes Fluorides

RCH3 0.9 FCH 4.24.8R

2

CH2

1.3 ChloridesR3CH 1.5 ClCH 3.14.1

ClAlkenes ClCH 5.8

C = CH 4.65.9C = CCH3 1.52.5 Bromides

BrCH 2.54.0

AlkynesC CH 1.72.7 IodidesC CCH3 1.62.6 ICH 2.04.0

NitroalkanesO2NCH 4.24.6

NMR


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NMRFunctional Chemical Functional Chemical

Group Shift, ppm Group Shift, ppm

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Alcohols Carboxylic AcidsHCOH 3.44 O

ROH 0.55.0 HOCCH 2.12.6

Phenols O

ArOH 4.07.0 R COH 11.012.0

AminesRNH2 0.54.0 Ketones

Ethers O

ROC - H 3.23.8 RCCH 2.12.4

Acetals

RO R Aldehydes

C 5.3 O

RO H RCH 9.010.0

Esters Amides

O O

ROCCH 3.54.8 RCNH 5.09.0

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NMR SpinSpin Splitting

In addition to the Chemical Shift and Signal Area, the

NMR spectrum can provide information about thenumber of the protons attached to a Carbon atom.

Through a process called Spin-Spin Splitting, a Protonor 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 adjacentatoms.

Spin - Spin splitting is the result of the interaction orcoupling of the +1/2 & -1/2 spins of the protons onthe adjacent carbon atoms.

Spin - Spin coupling effects are transferred primarilythrough the bonding electrons

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NMR SpinSpin Splitting (Cont)

Those Protons on the adjacent Protons aligned with

the applied magnetic field (+1/2 spin state), willtransfer 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 toincrease slightly

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NMR SpinSpin Splitting (Cont)

If the spins of the adjacent Protons are opposed to

the magnetic field (-1/2 spin state), the strength ofthe applied magnetic field around the sensing protonis slightly decreased

With a reduced applied magnetic field strength, the

secondary diamagnetic field is better able to shieldthe Proton from the applied field resulting in a slightdecrease in the Chemical Shift (increased ResonanceFrequency)

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

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NMR


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NMR Spin-Spin Splitting (Cont)

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1,1,2-Trichloroethane Tert-Butyl Methyl Ether

(a)

(a)

(a) (b)

All protons chemically equivalent(a) protons & (b) protons are separated by more thanthree (3) bonds

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

Possible spincombinations ofadjacent protons

Net Spin+1 0 -11 2 1

+1/2 -1/21 1 Signal Intensity

0

TMS

b

3H

a

9H

NMR


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NMR Spin-Spin SplittingAn example

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1,1,2-Trichloroethane

NMR


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NMR Spin - Spin Splitting - Multiplet Signal Intensities

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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

Pascals Triangle

0 Singlet

1 Doublet

2 Triplet

3 Quartet

4 Quintet

5 Sextet

6 Septet

Intensity ratios derived from the n + 1rule

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

The relative intensities of the outersignals in sextet & septet multiplets arevery weak and sometimes obscured.

(a)

(a)

(b)

(b)

Intensity 1 3 3 1

No.

AdjacentProtons

No.

PeaksSeen Relative

Intensity

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NMR Spin - Spin Splitting - Common Splitting Patterns

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X CH CH Y(X Y)

CH2 CH

X CH2 CH2 Y(X Y)

CH3 C H

CH3 CH2

CH3CH

CH3

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)

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NMR Spin - Spin Splitting - Isomer Example

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1-Chloropropane

2-Chloropropane

CH3 CH2 CH2 Cl

(a) (b) (c)

Cl

CH3 CH CH3

(a)

(b)

(a)

3 signals

2 signals

Signal Rel Chem Rel Signal Neighbors MultiplicityShift Area

a lowest 3 2 3 (Triplet)

b middle 2 5 6 (Sextet)

c highest 2 2 3 (Triplet)0 ppm

0 ppm

a

bc

a

bSignal Rel Chem Rel Signal Neighbors Multiplicity

Shift Areaa lowest 6 1 2 (Doublet)b highest 1 6 7 (Septet)

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Spin - Spin Splitting - Coupling Constant

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

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

The Coupling Constant has different magnitudes fordifferent types of protons

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H

HH 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

Ortho

6-10 Hz

para

1-4

Hz

meta

0-2 Hz

8-10 Hz

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

e,e 0-5 Hz

cis 6-12 Hz

trans 4-8 Hz

cis 2-5 Hz

trans 1-3 Hz

5-7 Hz

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Magnetic Equivalence

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They behave as an integral group.

Protons attached to the same carbon atom and have the same chemicalshift 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 HAproton.

Protons that have the same chemical shift and are coupled equivalentlyto 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


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Differentiation of Chemical and Magnetic Equivalence

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Br

CH3Br HA

HBCH3

Cyclopropane Compound

Two geminal protons (HA& HB) are chemically equivalent, butnot magnetically equivalent

Proton HAis on same side of ring as two halogens

Proton HBis 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

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Differentiation of Chemical and Magnetic Equivalence (Cont)

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

Protons HA& HBhave different chemical shifts

Each has different coupling constant with HC

Constant JACis a ciscoupling constant

Constant JBCis a transcoupling constant

Therefore, HA& HBare not magnetically equivalentThey do not act as group to split proton HC

HBsplits HCwith constant JBC into a doublet

HAsplits each component of doublet into doublets with coupling constantJAC

C = C

HB

HA HC

X

Vinyl Compound

NMR


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

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Ha& Hbchemically equivalent, butnot magnetically equivalent.

Each has different chemical shift.

Each has different coupling constantwith Hc.

Hbsplits Hcinto doublet (Jbc).

Hathen splits each Jbcdoublet into adoublet.

Similary, Hasplits Hcinto doublet (Jac).

Hbthen splits each Jacdoublet into adoublet.

Hcsplits Ha& Hb into doublets.

Ha& Hbeach then split thesedoublets.

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Aromatic Compounds (Substituted Benzene Rings)

We have previously stated that a magnetic fieldapplied to an Aromatic ring becomes non-uniform(anisotropic) by the stabilizing effect of the BenzeneRing Current resulting in the protons beingdeshielded(electron density becomes less); thus,

increasing the chemical shift. i.e., the absorptionsignal (Resonance Frequency) moves to the left onthe chartin the vicinity of 7.0 ppm.

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

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NMR


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Some groups, such asCyano, Nitro, Carboxyl,Carbonylare electron-withdrawing(deactivate the

ring), decreasing the electron density, and resultingin an increase in the Chemical Shift, i.e., resonancefrequency moves further down field.

For Electron-Withdrawing groups the Ortho & Para

protons lose more electron density that the Metaprotons; thus, are less shielded moving (increasing)the chemical shift downfieldrelative to the Metaprotons.

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NMR


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Aromatic Compounds (Substituted Benzene Rings) (Cont)

Electron-donating groups such asMethyl, Methoxy, Amino,Hydroxyactivatethe ring and increase the electron densityresulting in a decrease in the Chemical Shift, i.e., resonancefrequency moves up field to the right.

For ElectronDonating groups, the Ortho & Para protons gainmore electron densitythan the Meta protons; thus are moreshieldedmoving (decreasing) the chemical shift up field slightly

from the Meta protons.

MonoSubstituted 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 nearidentical chemical shifts resulting in a slightly broad singlet(the protons are not quite chemically equivalent).

See pattern A on slide 7311/10/201

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NMR


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Aromatic Compounds (Substituted Benzene Rings) (Cont)

MonoSubstituted Aromatic Rings (Cont)

In general, electron withdrawing groups (Cyano, Nitro,Carboxyl, Carbonyl) decrease the electron density of theOrtho & Para protons more so than the Meta protons,resulting in the signal for the O & P protons being slightlymore downfield than the Signal for the Meta protons as seenin pattern C on slide 73).

In the case of electron withdrawing groups with double bondssuch as Nitro (NO2) and Carbonyl (C=O) groups, or otherdouble bonds attached directly to the ring, MagneticAnisotropy causes the Ortho protons to be much moredeshielded than the Para & Meta protons, resulting in theOrtho protons having a significantly increased Chemical shiftas 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 upfield from the Meta protons as seen in pattern B on slide 73.

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NMR


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Aromatic Compounds (Substituted Benzene Rings) Cont)

MonoSubstituted Aromatic Rings (Cont)

For Monosubstituted Electronegative elements, such asHalides, which are electron withdrawing due to the Dipoleeffect, the electron withdrawing effect is less dominant thanthe 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 Shiftsignal movesup field as seen in pattern E on slide 64.

Note: The m/p signal is actually an overlapping of the mand p signals with the p signal slightly up field from

the m signal.The o proton has more electron density than the pproton because of the Magnetic Anisotropy effects of thering current.

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NMR


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Aromatic Compounds (Substituted Benzene Rings) Cont)

ParaDisubstituted Rings

P-Disubstituted patterns are generally easy to recognize.

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

If the two p-substituted groups are identical, the fourremaining protons on the ring are chemically and magneticallyequivalent producing a singlet as seen in pattern F (a) onslide 73.

If the two p-substituted groups are different, the protons onone 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 differentdepending on the relative electronegativity of the twosubstituted groups as seen in patterns F (b) & F (c) on slide73.

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NMR


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Common Aromatic Patterns

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NMR


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Activating and Deactivating groups and the impact ofthe changing electron density in the Benzene ring on

Chemical Shift of ortho, meta, para protons

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Methoxyl (0-CH3) group is ElectronDonating, activates ring by addingelectron density to o/p protons.

Chemical Shifts,

, of ring o/pprotons are moved up field, i.e.,

decreasing ppm because ofincrease electron density.

Note location of Methyl Protonsabsorption at 3.7 ppm (withoutinfluence of O it would be around1 ppm).

m o, p

m

m

p o

o

3 Methyl Protons

Anisole (C7H8O)

NMR


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m o/p

The Amino group is Electron Donatingand Activates the ring.

Increases electron density aroundOrtho & Paraprotons relative to Meta.

Chemical Shift,,of ring protons is up

field, decreased ppm

o

m

m

op

2 Amino

Protons

Aniline (C6H7N)

NMR


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Nitro group is electron withdrawing anddeactivates the ring.

Protons in ring are deshielded movingChemical Shift downfield.

Magnetic Anisotropy causes the Orthoprotonsto be more deshielded than the Para & Metaprotons.

p m

o

o

m

m

p

o

Nitrobenzene (C6H5NO2)


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NMR


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Activating and Deactivating groups and the impact ofthe changing electron density in the Benzene ring onChemical Shift of ortho, meta, para protons

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c

b a

The Methoxy group ismoderately activating,while the Nitro groups arestrongly deactivating

(electron withdrawing) Net effect is to Decrease

the electron density aboutthe ring protons

The a & b protons areOrtho to the stronglydeactivating Nitro groups,thus, they have reducedelectron density and theirChemical Shift is down

field relative to the cproton

All protons interact toproduce Spin-SpinCoupling.

ab c

3H

2,4-Dinitroanisole (C7H6N2O5)

NMR


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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 adjacentcarbon atoms to give spin- spin splitting.

Solvent effect - The absorption position is variablebecause these groups undergo varying degrees ofhydrogen bonding in solutions of differentconcentrations.

Amount of hydrogen bonding can radically affect thevalence electron density producing large changes inchemical shift.

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NMR


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Protons attached to atoms other than carbon atoms(Cont)

Absorption signals are frequently broad relative toother singlets, which can be used to help identify thesignal.

Protons attached to Nitrogen atoms often show

extremely broad signals and can be indistinguishablefrom the base line.

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Typical Ranges for Groups with Variable Chemical Shifts


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NMR


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NMR Spectra at Higher Field Strengths (Cont)

For example, a proton group resonating at 60 Hz in a

60 Mhz instrument would resonate at 100 Hz in the100 Mhz instrument.

This effectively stretches the X-axis scale improvingresolution.

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

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NMR


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Chemical Shift Reagents

Interactions between molecules and solvents, such as

those due to hydrogen bonding can cause largechanges in resonance positions of certain types ofprotons, such as hydroxy (OH) and amino (NH2).

Changes in resonance positions can also be affected

by changing from the usual NMR solvents, such aschloroform (CCL4) and deuterochloroform (CDCl3) tosolvents like benzene which impose local anisotropiceffects on the surrounding molecules.

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

Most chemical shift reagents are organic complexes ofthe Lanthanide elements.

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NMR


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Chemical Shift Reagents (Cont)

When added to a compound, these complexesproduce profound chemical shifts, sometimes up fieldand sometimes downfield, depending on the metal.

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

Cerium, praseodymium, neodymium, samarium,

terbium, and holmium shift resonances to the higherfield (lower ).

Another advantage of shift reagents is that shiftssimilar to those observed at higher fields can beinduced 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 theproton group and the concentration of the shiftreagent.

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NMR


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Example 1H1NMR Spectra

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Suggestions

For

Interpreting NMR Spectra

NMR Example Spectra


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NMR Spectra Interpretation Procedure

The following 4 slides provide a suggested process to

follow in attempting to interpret an NMR Spectra.

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

Note that each signal has a number associated with itrepresenting the area integration, i.e., the number ofprotons generating the signal.

Also note the expanded spectra of the signal at 2.6ppm. Expanded spectra are often provided when the

signal lacks sufficient resolution to clearly display thenumber of peaks being generated by the protons onthe carbon atom generating the signal.

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NMR Example Spectra


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The 2ndslide presents interpretations of each signalrelative to the number of protons (n) on the carbon

atom generating the signal and the number of protonsattached to adjacent carbons atoms that produce then+1 peaks comprising the signal as a result of spin-spin splitting.

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

The 4thslide ties it all together.

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NMR Example Spectra


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Four slides demonstrating a process for interpreting anNMR Spectra

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3H

Chemical Shift (

) in PPM

Note: Magnetic Field (Ho) increases

Slide 1

NMR Example Spectra


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Slide 2

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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-substituted

Benzene Ring

Doublet TripletFrom chemical shifts, peak

integration values, and splitting

patterns, develop substructures for

each signal.

NMR Example Spectra


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Slide 3

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Solve the Puzzle

NMR Example Spectra


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Slide 4

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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 Splitting

No. of peaks in a signal is equal

to the number of protons on all

adjacent carbon atoms plus 1

(N+1 rule)

5 protons on a

mono-substitutedBenzene Ring

3 protons on a

Methyl group

see 2 adjacent

protons

2 protons on a

Methylene group

see 4 adjacen

protons

sextet

quintet

doublet

1 proton on

Methine groupsees 5 adjacen

protons

3 protons on a

Methyl group

see 1 adjacentproton

triplet

NMR Example Spectra


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Benzyl Acetate (C9H10O2)

Methyl Protons (3)

No adjacent protons;

no splitting

Methylene Protons (2)

No adjacent protons;

no splittingAromatic Protons (5)

NMR Example Spectra


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Cyclohexene (C6H10)

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c

c

b

b

a

ac

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 the

electron rich bond.

The sets of 2 protonson 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 2overlapping triplets.

The 2 protons on each of

the equivalent b carbonssplit 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 Spectra


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2,5-Hexanedione (Acetonylacetone) (C6H10O2)

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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 SpectraCi Stilb (C H )


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Cis-Stilbene (C14H12)

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Aromatic Protons (10)

(very fine splitting)

Vinyl Protons (2)

Chemically & Magnetically Equivalent

Do Not Split

NMR Example Spectra


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Methyl Phenyl Acetate (C9H10O2)

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Aromatic Protons (5)

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

Chem Shift3.65 ppm

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

Chem Shift3.60 ppm

Note: 2 OverlappingAbsorptions!! Electronegative

Carboxyl Oxygen forces shift

of Methyl Proton absorptions

downfield to about same

location as shift of Methylene

Protons forced downfield by

effects of electronegative

Carbonyl group.

NMR Example Spectra4 H t (C H O)


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4-Heptanone (C7H14O)

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

The Methyl & Methylene group

protons on the left side of the

Molecule are Chemically & MagneticallyEquivalent to their counterparts on the

right side, thus, the Chemical Shifts are

the same and signals overlap

NMR Example SpectraI l B (C H )


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Isopropyl Benzene (C9H12)

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6H

1H

5H

1 proton sees6 protons

Producing Septetn+1=6+1=7

6 protons see

1 proton

producing

Doublet

n+1=1+1=2

NMR Example SpectraP Nit t l (C H NO )


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P-Nitrotoluene (C7H7NO2)

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3H

Nitro group is strongly deactivating and

the Methyl group is weakly activating.The net withdrawing effect on benzene ring

moves the chemical shift downfield, the

Protons ortho to the Nitro group more so than

The protons ortho to the Methyl group.

P- Dibsubstitution

4H

NMR Example Spectra


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Phenacetin (C10H13NO2)

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n+1=0+1=1

(singlet)

n+1=3+1=4

(quartet)

2H

1H

3H

P-Disubstitutionn+1=2+1=3

(triplet)

3H

4H

NMR Example SpectraIsobutyric Acid (C H O )


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Isobutyric Acid (C4H8O2)

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n+1=1+1= 2

(doublet)

n+1=6+1=7

(septet)

CarboxylicProton

6H

1H1H

NMR Example Spectra4 Amino Acetophenone (C H NO)


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4-Amino-Acetophenone (C8H9NO)

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2 2

2

3

P-Disubstitution

3 Methyl protons see

0 adjacent protons

producing singlet

n+1=0+1=1

Chemical Shift moved

downfield because

of proximity toElectronegative

Carbonyl group (C=O)

Withdrawing Donating

NMR Example SpectraButyrophenone (C H O)


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Butyrophenone (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

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3

2

Propoxyl group is moderately

deactivating, deshielding oring protons more so than p

protons (aniostropic effect)

m protons are deshielded least

2

ortho

(2)

para, meta

(3)

NMR Example SpectraCyclohexanone (C H O)


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Cyclohexanone (C6H10O)

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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 quintets

overlappiing

a a

bb

c

NMR Example SpectraIsobutyl Acetate (C H O )


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Isobutyl Acetate (C6H12O2)

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6

2

2

3

Nonet DoubletTriplet

Singlet

1 proton sees

8 adjacent protons

producing (8+1) 9 peaks

3 protons see 0 protons on

Carbonyl carbon producing a singlet

6 protons see

1 adjacent proton

producing doublet

2 protons see1 adjacent proton

produces doublet

NMR (Carbon13) Carbon-13 Nuclear Magnetic Resonance


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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 13C6nuclear magnetic resonance.

Chemical Shift is most useful parameter derived from 13C6spectra.

Integrals (signal areas) are Unreliable and not necessarilyrelated to the relative number of 13C6atoms present.

Hydrogens attached to 13C6atoms cause spin-spin splitting,spin-spin interaction between adjacent carbon atoms israre.

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NMR (Carbon13) Carbon-13 Nuclear Magnetic Resonance


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Carbon-13 Nuclear Magnetic Resonance

The Chemical Shifts for 13C6spectra are reported by the

number of ppm (units) that the signal is shifted downfieldfrom TMS, just as in the proton NMR.

The 13C6scale ranges from 0 (TMS) in the upper (highermagnetic)_field to 225 ppm in the lower field.

Resonance signals are more distinct providing moreresolution.

Adjacent CH2 carbons have distinct resonance signals.

Unusual to find two carbon atoms in a molecule with thesame chemical shift unless they are chemically equivalentby symmetry.

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NMR (Carbon13) Coupled C 13 Spectra


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Coupled C-13 Spectra

In coupled C-13 NMR spectra, the spectra diagram

exhibits spin-spin splitting, similar to Proton NMR, butwith a significant difference

The splitting pattern exhibited by a particular C-13atom 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 adjacentcarbon atoms.

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NMR (Carbon13) Coupled C-13 Spectra - Example


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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

Carbons

1 Aromatic Ar1 Benzyl CH21 Methylene CH21 Methyl CH31 Carboxyl O=C-O

(See Slide 113)

CH2 C O CH2 CH3

O


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NMR (Carbon13) Broad-Band Decoupled 13C6 Spectra


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Broad Band Decoupled C6Spectra

Simple molecules such a Ethyl Phenyl Acetate can

yield interesting and useful structural information,namely the number of hydrogens attached to eachcarbon.

However, for larger molecules the spectra can become

very complex with overlapping splitting patterns. A broader range of 13C6spectra can be obtained if all

the protons are decoupledfrom the molecule byirradiating them simultaneously with a broad spectrum

of frequencies in the appropriate range.

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NMR (Carbon13) Broad-Band Decoupled 13C Spectra (Cont)


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Broad Band Decoupled C6Spectra (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, thecarbons at positions 2 & 6 produce a single signal,and the carbons at positions 3 & 5 also produce asingle signal.

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NMR (Carbon13) Carbon-13 Spectra for coupled and decoupled Ethyl


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p p p yPhenyl Acetate

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NMR (Carbon13) Chemical Shifts for Carbon-13 NMR


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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 (Carbon13) Carbon-13 Spectra (Proton Decoupled)


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Carbon 13 Spectra (Proton Decoupled)

2,2-Dimethylbutane

Six carbon atoms, but only 4 signals + solventsignals for CDCl3and 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 hydrogensattached, appears as a small (weak) signal at 30.4

ppm.

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Cont on next slide

NMR (Carbon13) Carbon-13 Spectra (Proton Decoupled)


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Carbon 13 Spectra (Proton Decoupled)

2,2-Dimethylbutane (Cont)

Methylene Carbon (d), signal at 36.5 ppm.

Relative size of signals gives some idea of numberof each type of carbon

Note: Signal at 28.9 ppm for 3 carbon atoms.

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2,2-Dimethylbutane

NMR (Carbon13) Aromatic Ring Methyl Substitution


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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 (Carbon13) Bromocyclohexane & Cyclohexanol


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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 fromthe electronegative element

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Bromocyclohexane

Cyclohexanol


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NMR (Carbon13) Toluene (Hydrogen Coupled Spectrum)


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( y g p p )

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

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

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Toluenea

NMR (Carbon13) Cyclohexanone


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y

Strong deshielding effect of carbonyl group.

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

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NMR (Carbon13) Symmetry - 1,2- & 1,3-Dichlorobenzene isomers


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y y , ,

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

signals. A plane of symmetry for 1,3-Dichlorobenzene defines

four (4) different Carbon atoms, producing foursignals

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1,2-Dichlorobenzene

1,3-Dichlorobenzene

NMR Summary NMR Summary Notes


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y

NMR - An instrumental technique to determine thenumber, type, and relative positions of certain atoms ina molecule.

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

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

Under these conditions the absorption of energy is

quantized producing a characteristic spectrum for thecompound.

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

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NMR Summary NMR Summary Notes (Cont)


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y ( )

1H1and

13C6have odd atomic number and/or atomic

mass; thus they have spin properties and are the twoprimary isotopes utilized in NMR.

1H1and

13C6have two spins states (+1/2 & -1/2).

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

Nuclei with -1/2 spin state oppose magnetic field.

Resonance - If radiofrequency (low energy, longwavelength) waves are applied to nuclei with spin inan applied magnetic field, the lower energy nucleialigned with the field absorb a quantized amount ofenergy, reverse direction, and become opposed to thefield.

The stronger the magnetic field, the greater the

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y ( )

An NMR instrument applies a constant radiofrequency

of 60, 100, or 300 MHz and applies an increasingmagnetic field strength.

A higher field strength instrument allows for cleanerseparation 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 aproton a quantitative value.

The Chemical Shift values are report in units of PartsPer Million (ppm).

Magnetic field, in Hertz, increases from left to right onchart 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 chemicalshift - one signal is produced.

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

60 MHz MHz



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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 shieldproton from applied magnetic field.

Electronegative elements produce an electronwithdrawing effect, deshielding the proton, resultingin a larger chemical shift, that is, a smaller magneticfield is required to induce resonance.

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

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

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

Each type of proton senses the number ofequivalent protons (n) on the carbon atom next tothe one it is bonded, and splits its resonance signalinto n+1 signals, a multipletSpinSpin Splitting.

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

The Coupling Constant has different magnitudes fordifferent types of protons.

Protons that have the same chemical shift and arecoupled equivalently to all other protons are

magnetically equivalent and do not show spin-spinsplitting.

For example: Protons attached to the same carbonatom that have the same chemical shift do not spliteach other.

In monosubstituted aromatic rings, all ring protonshave near identical chemical shifts resulting in asingle, but slightly broader single.

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Electron-withdrawing (electronegative) groups, such

as nitro, cyan, carboxyl, and carbonyl, deshield thering moving the chemical shift downfield (increase ).

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

Hydrogen on heteroelements - Protons on elementsother than carbon, such as, oxygen (hydroxyl,carboxyl, enols), nitrogen (amines, amides) do notcouple with protons on adjacent carbon atoms; thus

no spin-spin splitting.

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Solvent effect - The absorption position in variablebecause these groups undergo varying degrees ofhydrogen bonding in solutions of differentconcentrations.

The amount of hydrogen bonding can radically affectthe valence electron density producing large changes

in chemical shift. Chemical Shift Reagents - Chloroform,

Deuterochloroform, Organic Complexes of LanthanideElements.

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

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

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

Carbon-13 NMR - 13C6

has spin and produces NMRspectra.

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

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

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

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

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

Except for a few simple molecules, 13C6spectra canbecome very complex, making interpretation difficult.

Irradiation of the molecules simultaneously with abroad spectrum of frequencies decouples thehydrogens from the molecule producing a muchsimpler spectra.

Electronegativity, hybridization, and anisotropy effectsinfluence the chemical shiftt

Nmr Lecture

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