Organic Chemistry Laboratory

1
Organic Chemistry Laboratory

• Building A Toolset
• For
• The Identification of Organic Compounds

Physical Properties Melting Point Boiling Point Density Solubility Refractive Index Chemical Tests Hydrocarbons Alkanes Alkenes Alkynes Halides Alcohols Aldehydes Ketones Spectroscopy Mass (Molecular Weight) Ultraviolet (Conjugation, Carbonyl) Infrared Functional Groups NMR (Number, Type, Location of protons) Gas Chromatography (Identity, Mole )
2
Spectroscopy

• The Absorption of Electromagnetic
• Radiation and the use of the Resulting
• Absorption Spectra to Study the
• Structure of Organic Molecules

3
Spectroscopy

• Spectroscopy 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

4
The Electromagnetic Spectrum
Frequency (?)
High
Low
Energy (E)
High
Low
Wavelength (?)
Short
Long
3 x 108 Hz
1.2 x 1014 Hz
Frequency
3 x 1019 Hz
3 x 1016 Hz
2 x 1013 Hz
6 x 107 Hz
1.5 x 1015 Hz
1 x 109 Hz
3 x 1011 Hz
4 x103cm-1
1.25 x104cm-1
Wave Number
0.002 cm-1
2.5 x104cm-1
1 x109cm-1
10 cm-1
3 cm-1
1 x107cm-1
5 x104cm-1
667cm-1
0.01 cm-1
Cosmic ? Ray
Vacuum UV
Microwave
Infrared
X-Ray
Radio
Frequency
1 m
5 m
0.01 nm
10 nm
30 cm
1 mm
Wavelength
400 nm
200 nm
800 nm
2.5 ?
15 ?
Visible
Near Ultraviolet
Nuclear Magnetic Resonance
Vibrational Infrared
Blue
Red
5
NMR

• Nuclear Magnetic Resonance Spectroscopy
• NMR

6
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

7
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

8
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

9
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)
  Spin

10
NMR

• Nuclear Spin States (Cont)
• 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, -5/2
• 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 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 - 1/2

11
NMR

• Nuclear Spin States (Cont)
• 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

12
NMR

• Two Allowed Spin States for a Proton

Direction of an Externally Applied Magnetic Field
(Ho)
Ho
Spin 1/2 Aligned
Spin -1/2 Opposed
- 1/2 Opposed to Field
1/2 Aligned
E
?E
1/2 Aligned with Field
Ho
-1/2 Opposed
No Field
Externally Applied Magnetic Field Ho
Alignments
Eabsorbed (E-1/2 state - E1/2 state)
h? ?E f(Ho)
The stronger the applied magnetic field (Ho), the
greater the energy difference between the spin
states
13
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 ?,
  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

14
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

15
NMR

• Typically, 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

16
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

17
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

18
NMR

• Electron Density, Frequency of Angular Precession
  (Cont)
• 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

19
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.

20
NMR

• NMR Spectra Fourier Transform vs. Continuous
  Wave
• Fourier Transform (Cont)
• 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).

21
NMR

• NMR Spectra Fourier Transform vs. Continuous
  Wave (Cont)
• 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)

22
NMR

• NMR Spectra Fourier Transform vs. Continuous
  Wave (Cont)
• Continuous Wave (Cont)
• 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.

23
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

24
NMR

• NMR Spectra FT 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 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

25
NMR

• NMR Spectra Background Summary

• 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
26
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

27
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

28
NMR

• NMR Spectra The Chemical Shift (Cont)
• The Chemical Shift is reported in units of
• Parts Per Million (ppm)

• 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!

29
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

30
NMR

• NMR Spectra The Internal Reference Standard
• 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.

31
NMR

• NMR Spectra The Internal Reference Standard
• 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 gt 0 and will be downfield from the TMS
  signal.

32
NMR

• NMR Spectra Simple Example

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
(6)
Signal(singlet)
Absorption
Ethane
TMS
13 12 11 10 9 8 7 6 5 4
3 2 1 0
Chemical Shift ? (PPM)
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
33
NMR

• NMR Simple Examples

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).
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.
Toluene
34
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.

Chemicals giving rise to 1 NMR signal
Chemicals giving rise to 2 NMR signals
H
CH3
H
H
H
H
H
H
H
H
H
CH3
Cyclopentane
Benzene
Methyl Acetate
1,4 dimethyl benzene (p-xylene)
Acetone
1-Chloro Methyl Ether
35
NMR

• An Isomer Example C5H12O

Signals ? Rel Area
Value of Signal a
1 9 b gt 2
2 c 2
1
2-Dimethyl Propanol
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.
t-Butyl Methyl Ether
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.
36
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 523.
• Thus, 5 Aryl protons, 2 Benzyl protons, and 3
  Methyl protons

Phenylacetone
2.1 ppm (3 protons)
7.2 ppm (5 protons)
3.6 ppm (2 protons)
37
NMR

• NMR Spectrum Phenylacetone (103-79-7)

Methyl 3 Protons
Ring 5 Protons
Methylene 2 Protons
C9H10O
38
NMR

• Integrals (Signal Area) (Cont)
• 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 21 might
  be 2H1H or 4H2H 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 gt1 to obtain
  whole numbers.
• See example computation on next Slide.

39
NMR

• Integrals (Signal Area) (Cont)
• NMR Spectrum Benzylacetate (C9H10O2)

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
2.52 1.00 1.48 5 2 3 c
b a Each value multiplied by 2 to
obtain integral values
40
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

41
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 (OCH) 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

42
NMR

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

43
NMR

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

44
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

45
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

46
NMR

• Chemical Shift Impact of Electronegative
  Elements (Cont)
• 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

47
NMR

• Chemical Shift Impact of Electronegative
  Elements

Compound CH3X CH3F CH3OH CH3Cl CH3Br CH3I CH4 (CH
3)4Si Element X F O Cl Br
I H SiElectronegativity 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
0.93 ppm
3.49 ppm
Note The Chemical Shift of the Proton increases
as the distance from the
Electronegative Oxygen increases.
48
NMR
Chemical Shift values of typical Proton
environments and the effects of Electronegative
Elements on the Chemical Shift.
-OH, -NH
TMS
12 11 10 9 8
7 6 5 4
3 2 1 0 ? (ppm)
CH2F CH2Cl CH2Br CH2I CH2O CH2NO3
Methine (1H)
CH2Ar CH2NR2 CH2S C C H CH2 C
C CH C C
H
C CH2 C
Methylene (2H)
CHCl3
Methyl (3H)
O
Effects of Electronegativity
F gt O gt Cl N gt Br gt S gt 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.
49
NMR

• General Regions of Chemical Shifts

TMS
12 11 10 9 8
7 6 5 4
3 2 1 0 ? (ppm)
50
NMR

• Approximate Chemical Shifts
• Protons (1H1)
  Carbon (13C6)

Type of Proton Chemical Shift, ? (ppm)
Type of Carbon Atom Chemical Shift , ? (ppm)
a Chemical shifts of these protons vary in
different solvents and with temperature
51
NMR

• Functional Chemical Functional
  Chemical
• Group Shift, ppm Group Shift, ppm

TMS (CH3)4Si 0 Aromatic AR H 6.5
8.0 Cyclopropane 0 - 1.0 AR C H (benzyl) 2.3
2.7 Alkanes Fluorides RCH3 0.9 F C
H 4.2 4.8 R2CH2 1.3 Chlorides R3CH 1.5 Cl
C H 3.1 4.1 Cl Alkenes Cl
C H 5.8 C C H 4.6 5.9 C C CH3 1.5
2.5 Bromides Br C H 2.5
4.0Alkynes C ? C H 1.7 2.7 Iodides C ? C
CH3 1.6 2.6 I C H 2.0 4.0 Nitroalkane
s O2N C H 4.2 4.6
52
NMR

• Functional Chemical Functional Chemical
• Group Shift, ppm Group Shift, ppm

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 Amines R 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
53
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

54
NMR

• Spin Spin Splitting (Cont)
• 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

55
NMR

• Spin Spin Splitting (Cont)
• 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

56
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 n1 signals, where n
  is the number of Protons on the adjacent Carbon
  atom(s)
• The n1 value represents the number of unique
  combinations of the 1/2 and -1/2 spin states of
  the adjacent Protons

57
NMR

• Spin-Spin Splitting (Cont)

1,1,2-Trichloroethane
Tert-Butyl Methyl Ether
(a)
(a)
(b)
(a)
All protons chemically equivalent (a) protons
(b) protons are separated by more than three (3)
? bonds ?No signal splitting - 2 signals (a)
(b)
a 9H
b 3H
Possible spin combinations of adjacent protons
TMS
0
Net Spin
1 0 -1 1 2 1
1/2 -1/2 1 1
Signal Intensity
58
NMR

• Spin-Spin Splitting An example

1,1,2-Trichloroethane
59
NMR

• Spin - Spin Splitting - Multiplet Signal
  Intensities

Pascals Triangle
(a)
(b)
No.AdjacentProtons
No.PeaksSeen
Example Spectrum Ethyl group
CH3 CH2
RelativeIntensity
(a)
(b)
0 Singlet 1 Doublet 2
Triplet 3 Quartet 4 Quintet 5
Sextet 6 Septet
Note Relative Signal Intensities
?
1.83
3.20
spin 1/2
spin -1/2
Net Spin 3/2 1/2 -1/2 -3/2
Intensity
1 3 3 1
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.
There are 3 times as many protons with1/2 or -
1/2 spin arrangements than 3/2 -3/2 Therefore,
the signal intensities are greater.
60
NMR

• Spin - Spin Splitting - Common Splitting Patterns

Singlet
Doublet
No. signals produced based on the no. of adjacent
protons
2 signals (see 1)
2 signal(see 1)
?
?
Triplet
Quartet
2 signals(see 1)
3 signals(see 2)
?
?
3 signals(see 2)
3 signals(see 2)
Quintet
Sextet
2 signals(see 1)
CH3 C H
4 signals(see 3)
?
?
CH3 CH2
3 signals(see 2)
4 signals(see 3)
CH3 CH CH3
Septet
2 signals(see 1)
7 signals(see 6)
?
61
NMR

• Spin - Spin Splitting - Isomer Example

3 signals
1-Chloropropane
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)
a
b
c
0 ppm
2-Chloropropane
2 signals
a
Signal Rel Chem Rel Signal Neighbors
Multiplicity Shift
Area a lowest 6
1 2 (Doublet) b highest 1
6 7 (Septet)
b
0 ppm
62
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

H
H
a,a 8-14 Hz a,e 0-7 Hz e,e 0-5 Hz
H
Ortho 6-10 Hz
6-8 Hz
H
11-18 Hz
para 1-4 Hz
cis 6-12 Hz trans 4-8 Hz
6-15 Hz
H
meta 0-2 Hz
cis 2-5 Hz trans 1-3 Hz
0-5 Hz
H
4-10 Hz
8-10 Hz
5-7 Hz
H C C CH
0-3 Hz
63
NMR

• Magnetic Equivalence

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
B
A
C
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.
64
NMR

• Differentiation of Chemical and Magnetic
  Equivalence

Br
CH3
Br
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
65
NMR

• Differentiation of Chemical and Magnetic
  Equivalence (Cont)

HA
HC
C C
HB
X
Vinyl Compound
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
66
NMR

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

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.
67
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.

68
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.

69
NMR

• Aromatic Compounds (Substituted Benzene Rings)
  (Cont)
• 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 ElectronDonating 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 73

70
NMR

• Aromatic Compounds (Substituted Benzene Rings)
  (Cont)
• Mono Substituted Aromatic Rings (Cont)
• 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
  (CO) 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.

71
NMR

• Aromatic Compounds (Substituted Benzene Rings)
  Cont)
• Mono Substituted Aromatic Rings (Cont)
• 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.

72
NMR

• Aromatic Compounds (Substituted Benzene Rings)
  Cont)
• 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.

73
NMR

• Common Aromatic Patterns

74
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

Anisole (C7H8O)
75
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

Aniline (C6H7N)
76
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

o

• 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
Nitrobenzene (C6H5NO2)
77
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

78
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

2,4-Dinitroanisole (C7H6N2O5)
79
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.

80
NMR

• Protons attached to atoms other than carbon atoms
  (Cont)
• 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.

81
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.

82
NMR

• NMR Spectra at Higher Field Strengths (Cont)
• 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.

83
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.

84
NMR

• Chemical Shift Reagents (Cont)
• 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 f