CHAPTER 14

MASS SPECTROMETRY

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Learning Objectives
• Understand the origin of mass spectral data
• Understand what data mass spectrum instrumentation
provides to the chemist
• Interpret mass spectral data and propose reasonable
structures for small organic molecules

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Chapter Outline
• A mass spectrometer (14.1)
• Features of a mass spectrum (14.2)
• Interpreting mass spectra (14.3)
• Mass spectrometry in the organic synthesis laboratory
and other applications (14.4)

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14.1 Mass Spectrometry (MS)

• Analytical technique for measuring the mass-to-charge

ratio (m/z) of ions
• Most valuable analytical tool today for determining
accurate molecular masses
• Information about molecular formula and structure of a
compound can be obtained by analyzing its mass spectrum
• Allows sequencing of proteins to determine their
structures on a virtually single-cell scale

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14.1 Mass Spectrometry (MS)

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14.1 Mass Spectrometer

• Designed to do the following things:

• Convert neutral atoms or molecules into a beam of positive or
negative ions
• Separate the ions on the basis of their mass-to-charge (m/z)
ratio
• Measure the relative abundance of each type of ion

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14.1 First-Generation Mass Spectrometers

• Electron ionization mass spectrometry (EI-MS)

• Vaporized sample is bombarded with high-energy
electrons (70 eV) in an evacuated ionization
chamber
• Causes the stripping of electrons from sample molecules
• Positively charged ions that are accelerated by a series of
negatively charged accelerator plates
• Ions move into an analyzing chamber inside a magnetic
field that causes the ion beam to curve
• Radius of curvature of each ion depends on the charge
on the ion (z), its mass (m), the accelerating voltage,
and the strength of the magnetic field
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14.1 Mass Spectrometry Techniques
• Electron ionization mass spectrometry (EI-MS)
• Fast-atom bombardment mass spectrometry (FAB)
• Matrix-assisted laser desorption ionization mass
spectrometry (MALDI)
• Chemical ionization mass spectrometry (CI)
• Electrospray ionization mass spectrometry (ESI-MS)

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14.1 Introducing Samples

• Samples of less volatile liquids and solids may be

placed on the tip of a heated probe and then inserted
directly into the ionization chamber
• One can link a gas chromatograph (GC) or liquid
chromatograph (LC) directly to the mass spectrometer
• GC and LC can separate complex mixtures into pure fractions
that can enter the ionization chamber of the mass
spectrometer directly
• Enables mass determination of individual components

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14.1 Molecular Ion
• Radical cation formed by removal of a single electron
from a parent molecule in a mass spectrometer
• Radical cation: Species formed when a neutral molecule
loses one electron
• Example - When methane is bombarded with high-
energy electrons, an electron is dislodged from a
molecule to give a molecular ion at m/z 16

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14.1 Molecular Ion
• Electron lost in forming the molecular ion is determined
by the ionization potential of the atom or molecule
• Ionization potentials for most organic molecules are between
8 and 15 eV
• Radical cation is delocalized throughout the molecule
• Molecular formula of the parent molecule is written in
brackets with a plus sign to show that it is a cation and a dot
to show that it has an odd number of electrons

• At times, it is useful to depict the radical cation at a certain

position in order to better understand its reactions
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14.2 Mass Spectrum
• Plot of the relative abundance of ions versus their mass-
to-charge (m/z) ratio
• Cations with larger values of m/z are deflected less than those
with smaller m/z values
• Base peak: Results from the most abundant cation
• Assigned an arbitrary intensity of 100
• Relative abundances of all other cations are reported as
percentages of the base peak

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14.2 Mass Spectrum of Dopamine

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14.2 Partial Mass Spectrum of Dopamine

• Number of peaks recorded in the mass spectrum

depends on the detector sensitivity

HO NH 2

HO

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14.2.A Resolution
• Measure of how well a mass spectrometer separates
ions of different mass
• Low-resolution mass spectrometry
• Instruments capable of distinguishing among ions of different
nominal mass [ions that differ by one or more atomic mass
units (amu)]
• High-resolution mass spectrometry
• Instruments capable of distinguishing among ions that differ
in precise mass by as little as 0.0001 amu

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14.2 Resolution - Example
• C3H6O and C3H8O have nominal masses of 58 and 60
and can resolved by low-resolution mass spectrometry
• C3H8O and C2H4O2 both have nominal masses of 60
and can be distinguished by high-resolution MS

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14.2.B Presence of Isotopes
• Elements common to organic compounds, including H,
C, N, O, S, Cl, and Br, are mixtures of isotopes
• Exceptions - Fl, P, and I
• Example - Naturally occurring carbon is 98.90% 12C and
1.10% 13C
• There are 1.11 atoms of carbon-13 in nature for every 100
atoms of carbon-12

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Figure 14.3 - Mass Spectrum of Chloroethane

• Chlorine in nature is 75.77% 35Cl and 24.23% 37Cl

• Ratio of M to M + 2 peaks of approximately 3:1 indicates the
presence of a single chlorine in chloroethane, as seen in the
figure below

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Figure 14.4 - Mass Spectrum of 1-Bromopropane

• Bromine in nature is 50.5% 79Br and 49.5% 81Br

• Ratio of M to M + 2 peaks of approximately 1:1 indicates the
presence of a single bromine atom in 1-bromopropane, as
seen in the figure below

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14.2.B Mass Spectrum of Dopamine
• The mass spectrum of dopamine

• The small peak at m/z 154 from an ion 1 amu heavier

than the molecular ion of dopamine is the sum of four
separate peaks, each of amu 154
• Each peak corresponds to the presence in the ion of a single
heavier isotope of H, C, N, or O in dopamine
• Called an M + 1 peak as its peak corresponds to an ion 1 amu
heavier than the molecular ion
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Table 14.2 - Precise Masses and Natural Abundances of Isotopes
Relative to 100 Atoms of the Most Abundant Isotope

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14.2.C M, M + 2, and M + 1 Peaks
• Common elements giving rise to significant M + 2
peaks are chlorine, bromine, and oxygen
• Oxygen makes the major contribution to the M + 2 peak in
compounds containing only C, H, N, and O
• Sulfur is the only other element common to organic
compounds that gives a significant M + 2 peak
• Sulfur in nature is 95.02% 32S and 4.21% 34S

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14.2.C Comparison of M + 2 and M + 1 Peaks

• M + 1 peaks are not useful for accurate determinations

of molecular formulas
• Relatively low in intensity compared to the molecular ion
peak and are difficult to measure with any precision
• M + 2 peaks can be useful for getting a rough idea of
the number of carbons, oxygens, sulfurs, and halogens

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14.2.D Fragmentation of Molecular Ions
• Electrons with energies of 70 eV [approximately 6750
kJ (1600 kcal)/mol] are commonly used in EI to:
• Attain high efficiency of molecular ion formation
• Give reproducible mass spectra
• 70 eV energy is sufficient to dislodge one or more
electrons from a molecule and cause extensive
fragmentation
• Fragments may be unstable as well and, in turn, break apart to
even smaller fragments

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14.2.D Fragmentation of Molecular Ions

• Under a given set of ionizing conditions, fragmentation

pattern and relative abundances of ions are unique for
each compound and are characteristic of that compound
• Fragmentation patterns provide valuable information about
molecular structure
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14.2 Fragmentation of Molecular Ions
• Chemistry of ion fragmentation can be understood in
terms of the formation and relative stabilities of
carbocations in solution
• Where fragmentation occurs to form new carbocations, the
mode that gives the most stable carbocation is favored
• Thus, the probability of fragmentation to form new
carbocations increases in the following order:

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14.3 Interpreting a Mass Spectrum
• If no large M + 2 peak is present, the elements 18O, 34S,
37Cl, and 81Br are absent

• These are the only elements to give significant M + 2 peaks

• Find if the mass of the molecular ion is odd or even
using the nitrogen rule
• Nitrogen rule: If a compound has an:
• Even number (including zero) of nitrogen atoms, its
molecular ion will appear at an even m/z value
• Odd number of nitrogen atoms, its molecular ion will
appear at an odd m/z value

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14.3.A Mass Spectra of Alkanes
• Rules for interpreting mass spectra
• Fragmentation tends to occur toward the middle of
unbranched chains rather than at the ends
• Differences in energy among allylic, benzylic, 3°, 2°, 1°,
and methyl carbocations in gas phase are much greater than
the differences among comparable radicals
• Where alternative modes of fragmentation are possible, the
more stable carbocation tends to form in preference to the
more stable radical
• Unbranched alkanes fragment to form a series of
cations differing by 14 amu (a CH2 group), with each
fragment formed by a one-bond cleavage having an odd
mass number
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Figure 14.5 - Mass Spectrum of Octane

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Figure 14.6 - Mass Spectrum of 2,2,4-Trimethylpentane

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Figure 14.7 - Mass Spectrum of Methylcyclopentane

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14.3.B Mass Spectra of Alkenes
• Alkenes show a strong molecular ion peak and cleave
readily to form resonance-stabilized allylic cations
+
+
[CH 2=CHCH 2 CH2 CH3 ] • CH2 =CHCH2 + •CH2 CH3

• Cyclohexenes undergo fragmentation to give a 1,3-

diene and an alkene in a process that is the reverse of a
Diels-Alder reaction (Section 20.5)

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Figure 14.8 - Mass Spectrum of 1-Butene

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14.3.C Alkynes
• Alkynes show a strong molecular ion peak
• One of the most prominent peaks is from the delocalization-
stabilized 3-propynyl (propargyl) cation (m/z 39) or a
substituted propargyl cation

Mass Spectrum of 1-Pentyne

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14.3.D Alcohols
• Loss of H2O to give a peak that corresponds to M – 18
• Loss of an alkyl group from the carbon bearing the
—OH to give a delocalization stabilized oxonium ion
and an alkyl radical
• Oxonium ion is stable because of delocalization of charge

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Figure 14.10 - Mass Spectrum of 1-Butanol

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14.3.E Aldehydes and Ketones

• Characteristic pattern of aliphatic aldehydes and

ketones is cleavage of a bond to the carbonyl group
(α-cleavage)
• α-Cleavage of the aldehyde proton gives an M + 1 peak,
which helps distinguish an aldehyde from a ketone

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Mechanism 14.1
• Reaction occurs through a six-membered ring transition
state

• Example - McLafferty rearrangement of 2-octanone

gives 1-pentene and a radical cation at m/z 58, which is
the enol of acetone

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Figure 14.11 - Mass Spectrum of 2-Octanone

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14.3.F Carboxylic Acids
• α-Cleavage of the carboxyl group to give the ion
[COOH]+ at m/z 45

• McLafferty rearrangement
• Base peak is often the result of the McLafferty rearrangement
product

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Figure 14.12 - Mass Spectrum of Butanoic Acid

• m/z 88 - Molecular ion

• m/z 45 - [COOH]+
• m/z 60 - McLafferty rearrangement product

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Characteristic Fragmentation Patterns of Esters

• α-Cleavage

• McLafferty rearrangement

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Figure 14.13 - Mass Spectrum of Methyl
Butanoate

• m/z 102 - Molecular ion

• m/z 74 - McLafferty rearrangement
• m/z 71 and 59 - Result of a-cleavage

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14.3.G Aromatic Hydrocarbons
• Most of them show an
intense molecular ion
peak
• Toluene and most
alkylbenzenes show a
fragment ion at m/z 91

Mass spectrum of toluene

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14.3.H Amines
• Pattern for 1°, 2°, and 3° amines is β-cleavage

Mass spectrum of 3-methyl-1-butanamine

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14.4 Applications of Mass Spectrometry
• Routine molecule identification in the organic synthesis
laboratory in both industrial and academic settings
• Uses gas chromatography (GC-MS) and liquid
chromatography (LC-MS) as the primary methods
• Drug testing of athletes and advanced forensic science
• Use GC-MS to identify traces of pharmaceuticals or illicit
drugs in blood samples
• Luggage screening devices to identify traces of known
explosives

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