MASS

SPECTROMETRY

Prepared by:
Camille C. Abendanio, R.Ch.
College of Science
Pamantasan ng Lungsod ng Maynila

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OBJECTIVES
• To describe the different processes and techniques in mass spectrometry.

• To propose fragmentation mechanisms of different functional groups.

• To identify important peaks in the mass spectrum and assign molecular fragments to
these peaks.

• To obtain structural information given the exact molecular weight or the molecular formula
of an unknown compound.

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OUTLINE
I. Mass Spectrometers

II. Fragmentations of Functional Groups

III. Other types of Mass Spectrometry

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MASS SPECTROMETRY
• Determination of the structure of molecules on the basis of their fragmentation
patterns and fragment ions formed.

• Fragment ions – mass to charge (m/z) ratio

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MASS SPECTROMETER
• It is possible to determine the masses of individual ions in the gas phase.

The components of Mass Spectrometer

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MASS SPECTROMETER
I. Sample introduction

II. Ion Separation Methods

a. Electron Ionization (EI)

b. Chemical Ionization (CI)

c. Desorption ionization techniques (SIMS, FAB, MALDI)

d. Electrospray Ionization (ESI)

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MASS SPECTROMETER
I. Mass Analyzer
a. Magnetic Sector Mass Analyzer

b. Double-Focusing Mass Analyzer

c. Quadrupole Mass Analyzer

d. Time-of-flight Mass Analyzer

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MASS SPECTROMETER

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INTERPRETATION OF MASS
SPECTRA

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ODD- AND EVEN-ELECTRON IONS
• ODD-ELECTRON IONS
o Formed when a molecule loses electron
o Positively charged and a radical

• EVEN-ELECTRON IONS
o More stable fragment ions
o All electrons in the outer shell are fully paired
o Formed from odd-electron ions undergoing fragmentation
CH4+· → CH3+ + H·

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MASS SPECTRUM

Partial EI-MS of dopamine

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MOLECULAR ION AND BASE PEAK
• Molecular Ion Peak (M+ or M•+)
o Most valuable info of the mass
spectrum
o Molecular weight of the sample
molecule

• Base Peak
o Most stable fragment in the molecule
o Stability is dictated by certain factors
(e.g. hyperconjugation, resonance)

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FRAGMENT IONS
• M+1 and M+2 Peak
o Peaks due to isotopes

• Fragment Ion Peaks

o Due to fragmentation processes on
the molecules

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FRAGMENTATION PROCESS
I. Initial ionization event

Loss of electron from molecular orbitals:

1. Non-bonding orbital

2. Pi-bonding orbital

3. Sigma-bonding orbital

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FRAGMENTATION PROCESS
II. Fundamental Fragmentation Processes
A. Stevenson’s Rule
The most probable fragmentation is the one that leaves the positive charge on
the fragment with the lowest ionization energy.

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FRAGMENTATION PROCESS
II. Fundamental Fragmentation Processes
B. Radical-Site-Initiated Cleavage:
The bond to the next neighboring atom from the radical site is cleaved.

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FRAGMENTATION PROCESS
II. Fundamental Fragmentation Processes
B. Radical-Site-Initiated Cleavage:
The bond to the next neighboring atom from the radical site is cleaved.

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FRAGMENTATION PROCESS
II. Fundamental Fragmentation Processes
C. Charge-Site-Initiated Cleavage: Inductive Cleavage
Inductive cleavage involves the attraction of an electron pair by an electronegative
heteroatom that ends up as a radical or as a closed-shell neutral molecule.

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FRAGMENTATION PROCESS
II. Fundamental Fragmentation Processes
D. Two-Bond Cleavage
This involves cleavage of two bonds simultaneously. Elimination of a small,
even-electron neutral fragment.

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FRAGMENTATION PROCESS
II. Fundamental Fragmentation Processes
E. Retro Diels-Alder Cleavage
Unsaturated six-membered rings can undergo a retro Diels–Alder
fragmentation to produce the radical cation of a diene and a neutral alkene.

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FRAGMENTATION PROCESS
II. Fundamental Fragmentation Processes
F. McLafferty Rearrangement
A Hydrogen atom on a carbon 3 bonds atoms away from the radical cation of
a π-system is transferred to the charge site.

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GENERAL RULES FOR PREDICTING
PROMINENT PEAKS
1. The relative height of the molecular ion peak is greatest for the straight-chain
compound and decreases as the degree of branching increases.

2. The relative height of the molecular ion peak usually decreases with increasing
molecular weight in a homologous series. Fatty esters appear to be an exception.

3. Cleavage is favored at alkyl-substituted carbon atoms: the more substituted, the

more likely is cleavage.

4. Double bonds, cyclic structures, and especially aromatic (or heteroaromatic) rings
stabilize the molecular ion and thus increase the probability of its appearance.

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GENERAL RULES FOR PREDICTING
PROMINENT PEAKS
5. Double bonds favor allylic cleavage and give the resonance-stabilized
allylic carbocation. This rule does not hold for simple alkenes because of the
ready migration of the double bond, but it does hold for cycloalkenes.

6. Saturated rings tend to lose alkyl side chains at the α-bond. This is merely a
special case of branching (rule 3). The positive charge tends to stay with the
ring fragment.

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GENERAL RULES FOR PREDICTING
PROMINENT PEAKS
7. In alkyl-substituted aromatic compounds, cleavage is very probable at the
bond β to the ring, giving the resonance-stabilized benzyl ion or, more likely,
the tropylium ion.

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GENERAL RULES FOR PREDICTING
PROMINENT PEAKS
8. The C-C bonds next to a heteroatom are frequently cleaved, leaving the charge
on the fragment containing the heteroatom whose nonbonding electrons
provide resonance stabilization.

9. Cleavage is often associated with elimination of small, stable, neutral

molecules, such as carbon monoxide, olefins, water, ammonia, hydrogen
sulfide, hydrogen cyanide, mercaptans, ketene, or alcohols, often with
rearrangement.

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FRAGMENTATION PATTERNS
OF FUNCTIONAL GROUPS
Electron Ionization (EI) Method

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ALKANES, ALKENES, ALKYNES
• Strong M+ for linear compounds
• More stable carbocations (fragment ions)
leads to the base peak
• Cycloalkanes – loss of ethene (m/z = 28)
• Alkenes – loss of allyl carbocation (m/z =
41)
• Alkynes – loss of propargyl group (m/z =
39)
o Terminal alkynes – M – 1 (loss of H)

Mass spectrum of isobutane

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ALKANES, ALKENES, ALKYNES

Mass spectrum of cyclopentane

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ALKANES, ALKENES, ALKYNES

Mass spectrum of 1-pentene Mass spectrum of 1-pentyne

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AROMATIC HYDROCARBONS
• Tropylium ion (m/z = 91) for
substituted benzenes
• For larger substituents, a
McLafferty rearrangement is likely
to occur.

Mass spectrum of toluene

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AROMATIC HYDROCARBONS

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AROMATIC HYDROCARBONS

Mass spectrum of isopropylbenzene

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ALCOHOLS, PHENOLS, THIOLS
• Cleavage = C-C bond next to the O or
S group
• M+ peak is usually low for 1° and 2°
alcohols; absent for 3°
• Loss of –H2O group (m/z = 18)
• Phenols: loss of CO (m/z = 28)
• Peak at m/z = 31 – diagnostic peak for
1° ROH
• Thiols – characteristic peak at m/z =
47; loss of m/z = 34 (H2S)

Mass spectrum of 1-pentanol

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ALCOHOLS, PHENOLS, THIOLS

Mass spectrum of 2-methyl-2-butanol

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ALCOHOLS, PHENOLS, THIOLS

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ETHERS AND SULFIDES
• Aliphatic ethers have weak M+ peaks
• Modes of fragmentation:
o Cleavage of the C-C bond next to the oxygen atom (α-cleavage)
o C-O bond cleavage (loss of alkoxy radicals)
o Rearrangement of the fragment ions
• Fragmentation is more favorable in acetals and ketals than in ethers.

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ETHERS AND SULFIDES

Mass spectrum of diisopropyl ether

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ETHERS AND SULFIDES

Mass spectrum of 4-methylphenetole

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CARBONYL COMPOUNDS
Aldehydes
• M+ peak – observable, relatively weak
• M-1 due to loss of aldehydic H
• α-cleavage – acylium ion (R-C≡O+)
• Inductive cleavage
• McLafferty Rearrangement
• Aromatic aldehydes – loss of formyl
radical

Mass spectrum of pentanal

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CARBONYL COMPOUNDS
Ketones
• M+ peak – intense
• α-cleavage – acylium ion (R-C≡O+)
• Inductive cleavage
• McLafferty Rearrangement
• Base peak often results in the loss of
the larger alkyl group

Mass spectrum of butanone

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CARBONYL COMPOUNDS
Ketones
• Aromatic ketones
o Ortho effect - When a substituent and a hydrogen are in close proximity to
form a six-membered transition state, the loss of neutral molecules of H2O,
ROH or NH3 occurs.

o McLafferty Rearrangement
o Characteristic ArC≡O+

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CARBONYL COMPOUNDS
Esters
• Loss of the alkoxy group to form
R-C≡O+
• McLafferty Rearrangement

Mass spectrum of methyl butanoate

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CARBONYL COMPOUNDS
Carboxylic Acids
• M+ peak – generally weak but
observable
• Loss of –OH (m/z = 17)
• McLafferty Rearrangement for acids
containing γ-hydrogens
• COOH+ ion

Mass spectrum of butanoic acid

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AMINES
• M+ peak – weak or absent
• α-cleavage

• Loss of the largest branch from the α-C

atom is preferred
• Presence of m/z = 30 suggests 1° amine

Mass spectrum of ethanamine

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AMINES

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AMINES

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AMINES

Mass spectrum of diethylamine

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AMIDES
• M+ peak – observable
• α-cleavage
• Presence of m/z = 44 suggests 1° amide
• McLafferty Rearrangement for amides
with long acyl chains

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NITRILES
• M+ peak – too weak
• Loss of α-H – characteristic fragment of
nitriles
• For straight-chain nitriles (C8 and higher),
a peak at m/z = 97 is prominent
• McLafferty Rearrangement

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NITRILES

Mass spectrum of hexanenitrile

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NITRO COMPOUNDS
• M+ peak – too weak
• Presence of nitro group is indicated
by peaks at m/z = 30 (NO+) and m/z
= 46 (NO+2)

Mass spectrum of 1-nitropropane

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HALOGEN COMPOUNDS
• Alkyl chlorides and alkyl bromides: M++2 peak
o For Cl, M/M+2 is 3:1
o For Br, M/M+2 is 1:1
• Loss of –Br or –Cl
• Loss of HCl
• Rearrangement and loss of alkyl radical

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HALOGEN COMPOUNDS

Mass spectrum of 1-bromohexane

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HALOGEN COMPOUNDS

Mass spectrum of 2-chloroheptane

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