CH 908: Mass Spectrometry
Lecture 3
Interpreting Electron Impact Mass
Spectra – Continued…
Recommended: Read chapters 5,8 of
McLafferty
Prof. Peter B. O’Connor
Objectives for this lecture
•
Fragmentation pathways for radical molecular ions
– Alpha cleavage
– Inductive cleavage
– Elimination
– Rearrangements
• Fragmentation series
–
–
–
–
–
Alkanes
Aldehydes/Ketones
Alcohols/sulfides
amines
esters/amides
• Isomer differentiation
• The McLafferty rearrangement
Fragmentation Pathways
Radical Site Initiation
(a-Cleavage) - 1



This is particularly important for ions that
contain N or O atoms.
Electron pairing occurs by the transfer of an
odd electron from the bond alpha to the
atom carrying the charge and the transfer of
the odd lone pair electron to form a new
bond.
The remaining electron from the alpha bond
is lost on the radical that is eliminated as a
result of the bond breaking.
Radical Site Initiation
(a-Cleavage) - 2


In this type of fragmentation, the charge site
does not move but the radical site moves as
a result of the alpha bond breaking. In the
example below, C - X is the alpha bond
broken.
An example is the fragmentation of carbonyl
compounds:

C - X CO+ + X.
||
O+.

(X = H, R, OH, OR, Cl, NH2) aldehydes,
ketones, acids, esters, acid halides, amides
Mechanisms of Alpha Cleavage




X = H, R, OH, OR, Cl, NH2 for
aldehydes, ketones, acids, esters,
acid halides and amides.
m/z 30 is the base peak in primary
amine spectra
Primary alcohols give the m/z 31,
ethers often give m/z 45, 59 . . by
this reaction
The ease of loss of alkyl groups is
R1>R2>R3 where this is also the
order of decreasing size.
C4H3+.
C6H5+.
[M-H.]+
M+.
Charge Site Initiation
(Inductive Cleavage)
i-cleavage, C3H7+
α-cleavage, -C3H7•
i-cleavage, C2H5+
α-cleavage, -C2H5•
M+.
-O•
α-cleavage, -C2H5•
α-cleavage, -NH2•
M+.
[M-16]+.
characteristic of amides
[CH2OH]+
-C2H4 from 84
[M-H2O]+.
-CH3
M+. absent
α-Cleavage, -C3H7
[CH2OH]+
i-Cleavage
[C2H4OH]+
3 examples of [CH2OR]+ ions at
m/z 31, 59 and 87
?
α-Cleavage, -CH3
M+.
[CH2NH2]+ base peak of
primary amines
M+.
Loss of the
Largest Alkyl Radical -1
Where there is a choice of alkyl radicals that
can be lost in an alpha-cleavage, the largest
radical is lost preferentially followed by the next
largest, etc.
 Thus, the most intense peaks should be derived
from the loss of the largest alkyl radical.

Loss of the Largest Alkyl Radical - 2




The loss of H or an alkyl radical gives rise to
the following series of ions for different
classes of compounds
Aldehydes and ketones m/z 29, 43, 57, 71 .
..
Aldehydes usually give a fairly prominent
m/z 29 peak (CHO+) and a weaker [M - 1]+
peak.
Methyl ketones often give m/z 43 (CH3CO+)
as the base peak.
Loss of the Largest Alkyl Radical - 3

Alcohols and ethers m/z 31, 45, 59, 73 . . .
Primary alcohols typically give a m/z 31
peak (CH2OH+), often of fairly low
intensity.

Methyl ethers give m/z 45 peaks, again
often of low intensity (charge induced
fragmentation usually predominates).

Amines m/z 30, 44, 58, 72 . . . n-alkyl
amines often give m/z 30 as the base peak
whereas secondary and tertiary amines
often give m/z 44 and 58 as base peaks
together with m/z 30
C3H7 loss
C2H5 loss
CH3 loss
M+. absent
Loss of the largest alkyl radical
[M-C5H11]+
[M-C3H7]+
[M-CH3]+
M+.
Fragmentation Pathways
Fragmentation: Alkanes
Hexane shows the same fragmentation pattern as other
unbranched alkanes. Alkyl carbocations at m/z=15, 29, 43 and
57 Da provide the dominant peaks in the spectrum. The
m/z=57 butyl cation (M-29) is the base peak, and the m/z=43
and 29 ions are also abundant.
Chain branching clearly influences the fragmentation of this
isomeric hexane. The molecular ion at m/z=86 is weaker than
that for hexane itself and the M-15 ion at m/z=71 is stronger.
The m/z=57 ion is almost absent (try to find a simple
cleavage that gives a butyl group). An isopropyl cation
(m/z=43) is very strong, and the corresponding propene
radical-cation at m/z=42 (colored orange), produced by
elimination of propane, gives the base peak.
By having the six carbons of hexane closed to a ring, the
fragmentation is profoundly changed. To begin with, the
molecular ion at m/z=84 is much stronger than the
corresponding ions in the previous acyclic compounds. The
base peak at m/z=56 is produced by loss of ethene, so it is an
odd-electron ion (colored orange). The alkenyl cations at
m/z=41 & 27 are stronger than the corresponding alkyl
cations (m/z=43 & 29). The loss of methyl (m/z=69), and a
corresponding small m/z=15 ion obviously require some
hydrogen rearrangements.
Fragmentation: aldehydes and ketones
Pentanal displays a set of ions associated with the alkyl chain
(e.g. m/z=57, 43, 41, 29 & 27). The molecular ion at m/z=86 is
very weak, as is the M-1 ion at m/z=85 (aldehydes generally
show fragment ions involving loss of groups attached to the
carbonyl function). Thus, the m/z=29 ion is probably composed
of both ethyl and HCO cations. Odd-electron rearrangement ions
are observed at m/z=58 (possibly loss of CO) & 44
(rearrangement involving loss of propene).
The molecular ion at m/z=86 is more abundant than in the
previous aldehyde spectrum. The directive effect of the
carbonyl group on fragmentation is also apparent here. Loss of
carbonyl substituents by alpha-fragmentation include: loss of
methyl (M-15 at m/z=71) and loss of a propyl radical (M-43 at
m/z=43). These comprise the most prominent fragment ions.
The molecular ion at m/z=86 is about as strong as in 2pentanone. Because of the symmetry, ethyl groups are the
only carbonyl substituents that can be lost by an alphafragmentation. The strongest fragment ions are found at
m/z=57 (loss of an ethyl group) and m/z=29 (an ethyl
cation).
Fragmentation: Alcohols and Sulfides
In 1-pentanol the hydroxyl group is at the end of the fivecarbon chain. There are two significant odd-electron
fragment ions, one at m/z=70 (loss of water), and the other
at m/z=42 (loss of water and ethene). The fragment ion at
m/z=55 is probably due to a methyl radical loss from the
m/z=70 ion. The m/z=31 ion may be a protonated
formaldehyde ion, formed by alpha-fragmentation.
3-Pentanol shows three significant fragment ions. Alphafragmentation (loss of an ethyl radical) forms the m/z=59
base peak. Loss of water from this gives a m/z=41 fragment,
and loss of ethene from m/z=59 gives a m/z=31 fragment.
The molecular ion (m/z=90) is strong, and the presence of
sulfur is indicated by a larger than usual M+2 (m/z=92)
peak. This is true for the m/z=75 & 47 peaks as well. Loss
of methyl and ethyl radicals generate ions at m/z=75 & 61.
The odd-electron rearrangement ion at m/z=62 results from
loss of ethene. Finally, m/z=47 may be formed from
m/z=62 by loss of a methyl radical.
Fragmentation: Amines
The mass spectrum of 1-aminopentane is remarkably simple,
thanks to the directive influence of nitrogen. Alphafragmentation generates the m/z=30 even-electron cation,
which is the only significant fragment ion. The molecular ion
(m/z=87) is rather weak.
The mass spectrum of 3-aminopentane is only slightly more
complex than its isomer above. The molecular ion is very weak,
and alpha-fragmentation again provides the base peak
(m/z=58). Loss of ammonia from this ion generates the
m/z=41 ion.
The cyclic secondary amine, piperidine, has a more complex
mass spectrum. The molecular ion at m/z=85 is relatively
strong. Alpha-fragmentation of a hydrogen gives the M-1 base
peak. Because of the ring, alpha-fragmentation of a carbon
group does not result in a change of mass. This ring-opened
cation-radical may then lose an ethyl radical or ethene to give
respectively m/z=56 & 57 ions. Loss of an allyl radical from the
ring-opened molecular ion would produce the m/z=44 ion.
Fragmentation: Esters and amides
The molecular ion in the mass spectrum of ethyl acetate is
rather weak. The base peak results from an alphafragmentation of ethoxyl radical to give an m/z=43 ion. It is
interesting that the alternative alpha-cleavage to an M-15 ion is
very weak. The loss of water to generate the odd-electron ion
at m/z=70 is curious. Small methyl and ethyl ions are found at
m/z=15 & 29.
The isomeric ester, methyl propanoate, has a more abundant
molecular ion than ethyl acetate. The alpha fragmentation of
methoxyl radical generates the strong m/z=57 ion. Alphafragmentation of the ethyl group leads to both m/z=59 & 29. A
smaller methyl peak is also seen.
The stability of dimethylformamide (DMF) is evident in the
abundance of its molecular ion (m/z=73), which is also the base
peak. A small M-15 peak is observed, but the second most
abundant ion is loss of HCO by an alpha-cleavage (m/z=44).
Other ions at m/z=42, 30 & 28 are probably derived from the
m/z=44 ion.
What are these?
Isomer Differentiation
1,1,2,2-tetrafluoroethane. The
nearest large fragment ion to the
small molecular ion is at m/z=83, a
loss of 19 amu. This suggests loss of
fluorine. The m/z=51 ion represents
half the molecule. A hydrogen shift
is necessary to explain the m/z=33
ion.
1,1,1,2-tetrafluoroethane. Important
differences from isomer 1 are that
the m/z=51 ion is much smaller,
m/z=33 is much larger, and a new
strong ion at m/z=69 has appeared.
Since fluorine is present, this may
be assigned as a trifluoromethyl
cation.
Allylic Cleavage


This is a major type of fragmentation for alkenes
leading to alkyl radical loss. Unfortunately, migration
of the double bond occurs before fragmentation so
that the observation of ions of this type is of little
structural value. The mass spectra of many alkenes,
especially polyenes, tend to be independent of the
position of the double bond so that isomers cannot
be distinguished.
The m/z 41 ion is the most common ion observed in
the mass spectra of aliphatic compounds, together
with homologues of m/z 55, 69, 83 . . .
Allylic ions at m/z 41, 55, 69, 83
M+.
Charge Site Initiation
(Inductive Cleavage)
Pentene
elimination
followed by
alpha cleavage
[HOCH2]+
[-C2H5]+
3e rearrangement
Pentene
elimination
followed by
H• loss
C3H7+
C2H5+
i
i
M+.
[-CH3]
α
Pentene elimination
[-C2H5]
3e rearrangement
C3H7+
i
[C2H3]+
α
[-CH3]
M+.
i
[-CH3]
α
Rearrangement Reactions
McLafferty Rearrangement – 1
γ-H rearrangement
McLafferty Rearrangement – 2
γ-H rearrangement
Deuterium labelling studies show that a g-H atom
is transferred quite specifically through a sixmembered transition state. If there are no g-H
atoms, the rearrangement does not occur.
 Note that substituents on the a-carbon atom are
retained in the ion but substituents on the b- and gcarbon atoms are lost as part of the alkene - useful
in locating site of branching in an alkyl chain.

[C2H5CO]
+
No alkyl chain 3 or more C atoms
long so no McLafferty
Rearrangement leading to alkene
loss
[C2H5]
+
M+.
[C3H7]+,
[CH3CO]
+
C2H4 loss from C3H7 alkyl chain
CH3 loss
M+.
Loss of C4H8 from
C5H11 alkyl chain
[MC5H11]+
[M-OCH3]+
M+.
Loss of C4H8 from
C5H11 alkyl chain
[M-NH2]+
M+.
McLafferty Rearrangement – 3
γ-H rearrangement


If an even mass fragment ion is found which
could be formed from the molecular ion by
the loss of 28, 42, 56, 70, . . . Da., always
suspect that it results from a McLafferty
rearrangement or of a related process.
The driving force for the rearrangement is
the formation of a strong bond between the
H atom and the unsaturated heteroatom
carrying the charge. Similar reactions
occur with H-transfer to other heteroatoms.
Self Assessment
• In a long chain fatty acid, draw an inductive cleavage
mechanism and an alpha cleavage mechanism.
• Also draw the Mclafferty rearrangment for the long
chain fatty acid. What masses would be expected?
• A peak at m/z 31 suggests what moiety? 47?
• List two ways that isomers can be differentiated in
mass spectrometry.
• Can stereoisomers be differentiated using MS?