Mass Spectrometry

i. Introduction

Mass spectrometry is the technique most commonly

used to measure the mass of molecules (usually
organic molecules, including biomolecules), and can
therefore help to characterize a particular molecule
or to identify an unknown. Mass spectrometry can
also be used to generate information about the
structure of a molecule.
In electron ionization (EI) mass spectrometry, a
small sample of a chemical compound is
vaporized, bombarded with high energy
electrons to ionize the sample, and the ions
produced are detected based on the mass to
charge (m/z) ratio of the ions.
The electron ionization (EI) mass spectrum of an
organic compound can provide valuable information
regarding the molecular mass of the compound in
question determined from the molecular ion (M+) signal
(usually the most intense high molecular weight signal in
the spectrum), and the presence (or absence) of a given
functional group or groups plus structural details from
an analysis of the major fragment ions revealed in the
spectrum.
For many classes of organic compounds, however,
the molecular ion is quite unstable and decomposes
before it can reach the detector. As a result,
molecular ions for these types of compounds are
absent from the spectrum, and valuable
information is lost. To overcome this potential
problem, another type of mass spectrometry can be
used. In chemical ionization (CI) mass
spectrometry, the sample is vaporized along with a
reagent gas, usually methane.
The ionization chamber ionizes the methane and
not the sample. Ion-molecule collisions result in
the formation of CH5+, a strong Lewis acid. This
acid can protonate the sample yielding an ion
that is one mass unit heavier than the molecule
itself. This new ion can be detected, resulting in
an M+1 signal (which is the molecular weight of
the sample plus one).
 ii. Instrumentation
A mass spectrometer is composed of an inlet system
(which introduces the sample to the instrument and
vaporizes the sample), a molecular leak (which produces a
steady stream of the vapor), an ionization chamber (where a
beam of high energy electrons bombards the vapor), a mass
analyzer (a series of charged plates which focuses and
accelerates the beam of ions into a curved tube with an
applied magnetic field which separates the ions by mass), a
detector (a simple counter which produces a current every
time an ion strikes it), and a recorder (which produces the
mass spectrum. A schematic for a typical mass spectrometer
is shown in Figure 1.
 iii. The Molecular Ion
Perhaps the most crucial piece of information obtained
from the mass spectrum is the molecular mass of the
compound in question. Structure elucidation requires
knowledge of the chemical formula, and this can
often be ascertained from the mass. The molecular ion
(M+, that ion detected in mass spectrometry due to the
loss of one electron from the molecule) provides the
molecular mass of the compound directly. The sections
below enumerate salient points to consider when
interpreting EI mass spectra containing this important
ion.
 A. The ionization process
In mass spectrometry, a small sample of a
chemical compound is vaporized, bombarded
with high energy electrons to ionize the sample,
and the ions produced are detected based on
the mass to charge ratio (m/z) of the ions. A
typical ionization process is shown in Scheme 1
for benzamide.
Scheme 1.
Several different types of ions can be produced during this
process. If the compound loses only one electron, then a
molecular ion (frequently symbolized by M+), having the
same mass as the original compound, is produced (see
Scheme 1).
This m/z of the molecular ion gives the nominal
molecular weight of the compound. The stream of high
energy electrons is sufficiently powerful so that chemical
bonds in the molecule may be broken, producing a series
of molecular fragments.
These positively charged fragments are also
detected by the instrument, producing the mass
spectrum. Organic chemical compounds will often
fragment in very specific ways depending upon
what functional groups are present in the molecule
(see Scheme 2 for the common fragments produced
by benzamide). Analysis of the fragmentation
pattern can lead to the determination of the
structure of the molecule.
Scheme 2. Fragments produced from the
molecular ion of benzamide.
The complete mass spectrum of benzamide is given
in Figure 1. Notice the appearance of the predicted
molecular ion (Scheme 1) and the various fragment
ions (Scheme 2) that are revealed in the spectrum.
Note also that there are many other fragments with
various m/z values that are not necessarily readily
interpretable. The main goal of any analysis should
be the explanation of at least the most abundant
ions revealed by the mass spectrum.
Figure 1. Mass spectrum of benzamide.
The observed % abundance (we usually refer to
intensity when we are speaking of signals) of the
suspected molecular ion must correspond to
expectations based on the assumed molecular
structure.
Molecules containing - or non-bonding electrons
are less likely to fragment readily and will often
yield intense signals for M+ ions in the spectrum.
Conversely, highly branched molecules (which can
generate relatively unstable tertiary radical cations)
or molecules that can lose neutral stable radicals
(like halides) will give less intense or completely
absent signals for M+. The relative abundance of
the molecular ion will usually correspond to the
following sequence:
 B. The Nitrogen Rule
If a compound contains an even number of nitrogen
atoms (or no nitrogen atoms), its molecular ion will
appear at an even mass number. If, however, a
compound contains an odd number of nitrogen
atoms, then its molecular ion will appear at an odd
mass value. This rule is very useful for determining
the nitrogen content of an unknown compound. In
the case of benzamide (Figure 1), the molecular ion
appears at m/z 121, indicating an odd number of
nitrogen atoms in the structure.
 C. Molecular Formula Determination
The molecular ion gives the nominal molecular weight of
the substance. To determine the chemical formula (or a
series of possible chemical formulas), one can use the rule
of 13.
The Rule of Thirteen is so named because, to generate a
base formula (containing only carbon and hydrogen); the
molar mass of the substance is divided by 13. The
numerator from division gives the number of carbon
atoms in the base formula. The remainder, when added
to the numerator, gives the number of hydrogens in the
base formula.
 MW / 13 = n + r / 13
The base formula becomes CnHn+r that is a
combination of carbons and hydrogens having
the desired molecular weight, MW. One can
then calculate the Index of Hydrogen Deficiency
(IHD) for this formula using the following
equation:
The index of hydrogen deficiency (unsaturation
index),U, that corresponds to the preceding
formula is calculated easily by applying the
relationship
Special attention should be paid to the IHD calculation,
because impossible IHDs (negative or fractional) can lead
to the rejection of one or more possible chemical
formulas. Of course, the compound may contain other
elements besides carbon and hydrogen. To account for
other elements present, the appropriate number of
carbons and hydrogens that equals the molar mass of the
desired element is subtracted from the base formula to
account for the added element(s). Table 1 shows the
carbon/hydrogen equivalents for some of the more
common elements.
Table 1. Carbon/Hydrogen equivalents for some of the more
common elements found in organic compounds .

Subtract
Add Element DIHD
Element
C H12 7
H12 C -7
O CH4 1
O2 C2H8 2
O3 C3H12 3
N CH2
N2 C2H4 1
S C2H8 2
35Cl C2H11 3
79Br C6H7 -3
79Br C5H19 4
F CH7 2
Si C2H4 1
P C2H7 2
I C9H19 0
I C10H7 7
In the benzamide example, applying the rule of
thirteen results in a base formula of C9H13 (IHD =
3.5). Since this formula has an impossible IHD
and the M+ is shown to have an odd mass, it is
reasonable to add nitrogen to the formula
(subtracting CH2) resulting in a new formula of
C8H11N (IHD = 4).
Other possible formulas (involving nitrogen and oxygen
are C6H7N3 (IHD = 5) and C7H7NO (IHD = 5).
Other spectral evidence (for instance IR and NMR data)
can be very useful in identifying specific elements to
include in this analysis.
Further analysis of the mass spectrum, the accurate mass,
or isotope ratio data is required to settle upon the correct
formula.
 D. Isotope Ratio Data

1. COMMON ELEMENTS IN ORGANIC

COMPOUNDS
ISOTOPE RATIO DATA
There are molecules present in the sample that contain
less abundant isotopes of carbon (13C), hydrogen (2H),
nitrogen (15N), and oxygen (18O), for example. Because
the mass spectrometer counts individual ions, those
ions derived from molecules with heavier than normal
isotopes will have heavier masses. These ions give rise
to additional observed ions at M + 1, M + 2, etc. In
Figure 1, ions at m/z 122 (M + 1) and 123
(M + 2) are easily observed.
These are due to the presence of isotopes of
carbon, hydrogen, nitrogen, and oxygen in
benzamide, and are forms of the molecular ion
(the lowest m/z ion is called monoisotopic
because it contains the lightest isotopes of the
constituent atoms).
In Figure 1, the ion found at m/z 122 can arise in
several ways: one carbon out of the seven
present could be 13C, one hydrogen out of the
seven present could be 2H, or the nitrogen atom
in the molecule could be 15N.
From the relative abundances of these isotopes
(see Table 3), it is straightforward to determine how
intense the signal for this M + 1 ion should be if the
chemical formula were C7H7NO: (7 x 1.11) + (7 x 0.016) +
(1 x 0.38) = 8.2%. In words, the M + 1 ion signal (m/z 122)
should be approximately 8% of the height of the signal for
the M+ ion (m/z 121). In Figure 1, the M+ ion signal has a
height of approximately 43.5 mm, and the M + 1 ion is
approximately 3.5 mm; thus, the M + 1 ion signal is 8%
relative height with respect to that of the M+.
Table 3. Relative isotope abundances for the elements most
common to organic compounds.

Relative Relative
Element Isotope Abundance Isotope Abundance
* *

Carbon 13C 1.11

Hydrogen 2H 0.016
Nitrogen 15N 0.38
Oxygen 17O 0.04 18O 0.2
Silicon 29Si 5.1 30Si 3.35
Sulfur 33S 0.78 34S 4.4
*As a percentage of the most common isotope.
The relative intensity of the M + 2 ion signal observed in
the mass spectrum is not as straightforward to determine.

There are multiple ways for a molecule of benzamide to

have a mass of 123: two of the carbon atoms could be 13C,
two hydrogen atoms could be 2H, one carbon atom as 13C
and one hydrogen as 2H, or the oxygen atom could be 18O.

For the sake of simplicity, the following equations can be

used to determine the relative intensities (with respect to
the M+) of the M + 1 and M + 2 ions:
%(M + 1) = (1.11 x #C atoms) + (0.016 x #H atoms) +
(0.38 x #N atoms) + ...

%(M + 2) = [%(M + 1)2 / 200] + (0.20 x #O atoms) +

(3.35 x #Si atoms) + (4.4 x #S atoms) + ...
For the benzamide example,
the %(M + 1) = (1.1 x 7) + (0.016 x 7) + (0.38 x 1)
= 8.2% and
the %(M + 2) = [(8.2)2 / 200] + (0.20 x 1) = 0.54%
according to these equations.
2. Bromine and Chlorine
When one bromine or chlorine is present in a compound,
the M + 2 ion becomes very significant. This is because
bromine is comprised of two isotopes (79Br and 81Br) in a
nearly 1:1 ratio in naturally occurring substances, and
chlorine has two isotopes (35Cl and 37Cl) in a 3:1 ratio.
If a compound contains bromine, the M+ and M + 2 ions are
present at almost equal intensities. Additionally, if a
compound contains chlorine, the M+ and M + 2 ions will be
present in a 3:1 ratio.
The presence of these M+ and M + 2 ions in these
ratios is indicative of brominated and chlorinated
compounds, and the patterns of the molecular ions
are a strong indicator of the presence of multi-
istopic elements (these patterns are particularly
useful in organometallic chemistry because many of
the metallic elements consist of a variety of
isotopes). Figure 2 contains the mass spectra of
chloroethane and bromoethane, respectively, to
illustrate the point.
Figure 2. Mass spectrum of chloroethane.
Notice the 3:1 of the M+:M + 2 ions
Figure 2.Mass spectrum of bromoethane.
Notice the 1:1 ratios of the M+:M + 2 ions
IV. Fragmentation Patterns for
Organic Functional Groups
Organic molecules will fragment in very specific
ways depending upon what functional groups
are present in the molecule. These fragments (if
positively charged) are detected in mass
spectrometry. The presence or absence of
various mass peaks in the spectrum can be used
to deduce the structure of the compound in
question.
A. Alkanes
 1. Straight Chain Alkanes
When an alkane is ionized by EI, it will lose an
electron to form a radical cation. This radical
cation has the same mass as the parent
compound (minus one electron) and is the
molecular ion (M+). The type of radical formed
follows the stability of radicals:
3o > 2o > 1o > methyl
The alkane molecular ion can further fragment
to form a homologous series of cations of mass
CnH2n+1. These cations arise from the loss of
methyl radical (M - 15), ethyl radical (M - 29),
etc. Scheme 3 shows a possible mechanism of
fragmentation for pentane; the corresponding
mass spectrum of pentane is given in Figure 3.
Scheme 3. Mechanism of fragmentation
for pentane
Notice the appearance of M - 15, M - 29, M - 43,
and M - 57 ions in Scheme 3. Table 5 shows the
typical fragments lost by acyclic alkanes and
their respective masses.
Table 5. Typical fragments lost from straight
chain alkanes.

Mass Lost Fragment Lost

1 H
2 2 H
15 CH3
29 C2H5

43 C3H7 -or- C2H4 & CH3

57 C4H9 -or- C2H4 & C2H5

71 C5H11 -or- C3H6 & C2H5

Figure 3. Mass spectrum of pentane.
Ions observed in the mass spectra of straight chain
alkanes will usually appear in groups of 14 mass unit
intervals (corresponding to one CH2 group difference).
The most abundant fragment ion is usually the 3 carbon
fragment, with the abundances of higher mass ions
decreasing with increasing mass. Often, the M - 15 ion
(formed by loss of methyl radical) will be absent. The
series of fragments to look for in these spectra are of
CnH2n+1+, CnH2n+, and CnH2n-1+. The mass spectrum of
n-hexadecane (Figure 4) illustrates these points.
Figure 4. Mass spectrum of n-hexadecane.
 2. Branched Alkanes
Branched alkanes tend to fragment very easily owing to
the presence of 2o, 3o, and 4o carbon atoms in the structure.
When branched alkanes fragment, stable secondary and
tertiary carbocations can form.
For this reason, the molecular ion is much less abundant
than for straight-chain alkanes. The most important mode
of fragmentation in branched alkanes usually occurs at the
branch point.
 Scheme 4 shows the mechanism of
fragmentation for isobutane, and the mass
spectrum for isobutane is contained in Figure 5.
Notice the reduced intensity of the molecular ion
(m/z 58).
Scheme 4. Mechanism of fragmentation for
isobutane.
Figure 5. Mass spectrum of isobutane.
 3.Cyclic Alkanes
The fragmentation patterns of cycloalkanes may show
mass clusters in a homologous series, as for the alkanes.
However, the most significant mode of cleavage of the
cycloalkanes involves the loss of ethylene from the parent
molecule or from intermediate radical-ions.
Additionally, if the cycloalkane has a side chain, loss of that
side chain is also a favorable mode of fragmentation.
Scheme 5 provides the mechanism for the fragmentation
for cyclohexane. The mass spectrum of cyclohexane (Figure
6) has an abundant ion of m/z 56 arising by the loss of
ethylene.
Scheme 5. Mechanism of fragmentation
for cyclohexane.
Figure 6. Mass spectrum of cyclohexane
Cycloalkanes will also give ions akin (similar) to
those arising from alkanes. For instance, the ion
of m/z 69 is due to the loss of methyl radical.
The ions of m/z 15, 29, and 43 are due to
methyl, ethyl, and propyl cations, respectively.
B. Unsaturated Hydrocarbons
 1. Straight Chain Alkenes
The mass spectra of most alkenes show distinct
molecular ions. This is probably due to the loss of a p-
bonding electron, leaving the carbon skeleton relatively
undisturbed. The most important fragmentation events
for alkenes involve cleavage of the allylic (favored) and
vinylic (less favored) carbon-carbon bonds. For terminal
alkenes, allylic fragmentation forms an allylic carbocation
of m/z 41. The fragmentation mechanism for 1-butene
shown in Scheme 6 illustrates these points. The complete
mass spectrum of 1-butene is given in Figure 8.
 Scheme 6. Mechanism of
fragmentation for 1-butene.
Figure 8. Mass spectrum of 1-butene.
Alkenes usually form fragments corresponding to
CnH2n+1+, CnH2n+, and CnH2n-1+ (the latter two
fragment ion series are more abundant). It is very
difficult to locate the position of the double bond in
an alkene because of the easy migration of the
double bond by hydride and hydrogen atom shifts. For
this reason, the mass spectra of alkene isomers are nearly
identical and almost impossible to distinguish, as is
illustrated in Figure 9, which contains the mass spectra
for 2- and 3-heptene, respectively.
Figure 9. Mass spectra of 2-heptene
Figure 9. Mass spectra of 3-heptene
 2. Cyclic Alkenes
The mass spectra of cycloalkenes show distinct molecular
ions. It may be impossible to locate the position of a
double bond due to migration. The mechanism of
fragmentation for cyclic alkenes is virtually the same as
for straight chain alkenes. One noteworthy characteristic
is the fragmentation of cyclohexenes to undergo a
reverse Diels-Alder reaction as indicated in Scheme 7. This
rearrangement is characteristic of many isoprenoid natural
products and of tetralin derivatives, and is useful for assigning
structure and distinguishing isomers. The complete mass
spectrum of cyclohexene is given in Figure 10.
Scheme 7. Mechanism of fragmentation
for cyclohexene
Figure 10. Mass spectrum of cyclohexene.
 3. Alkynes
The mass spectra of alkynes are virtually identical to
those of alkenes. The molecular ion is usually more
abundant, and fragmentation parallels that of the
alkenes. Two differences are worth mentioning:
terminal alkynes fragment to form propargyl ions
(m/z 39), and can also lose the terminal (or an a-)
hydrogen, yielding a strong M - 1 ion. These two
modes of fragmentation are outlined in Scheme 8
for 1-butyne, and the complete mass spectrum of
1-butyne is given in Figure 11.
Scheme 8. Mechanism of fragmentation for
1-butyne.
An alternative way to describe the loss of
hydrogen radical from an alkyne would involve a
1,2-hydride shift (converting a vinylic radical
cation to a more stable allylic radical cation)
that subsequently loses hydrogen radical to give
the M - 1 ion. This alternate mechanism is
outlined in Scheme 9.
Scheme 9. Alternate mechanism of
fragmentation for 1-butyne.
Figure 11. Mass spectrum of 1-butyne.
 Problems

Given the MS Spectra Draw the

structure of each
C. Aromatic Compounds
The mass spectra of most aromatic compounds
show distinct and abundant molecular ions. This
is probably due to the loss of an electron from
the system, leaving the carbon skeleton
relatively undisturbed.
When an alkyl side-chain is attached to the ring,
fragmentation usually occurs at the benzylic position,
producing initially a benzyl ion, which often rearranges to
the tropylium ion (m/z 91). However, fragmentation can
also occur at the attachment point to the ring producing
the phenyl cation (m/z 77).
If the side-chain is a propyl group or larger, then the
McLafferty rearrangement is a possibility, producing
a fragment of m/z 92. Formation of a substituted
tropylium ion is typical for alkyl-substituted
benzenes producing an ion of m/z 105. Each of
these possible fragmentation events is described in
Scheme 10.
Scheme 10. Mechanism of fragmentation for
propylbenzene.
The phenyl cation will fragment further. One route
involves the loss of acetylene yielding a fragment
with formula C4H3+ (m/z 51). Another route involves
the loss of presumably an allene diradical with
formula C3H2, forming probably the simplest
aromatic species of the formula C3H3+ (m/z 39), namely
the cyclopropenyl ion. A proposed mechanism for the
formation of these fragments is given in Scheme 11. Note
that this mechanism is complete conjecture, and only
serves as one possible explanation.
The complete mass spectrum of propylbenzene is given in
Figure 12, which illustrates all of these points.
Scheme 11. Proposed mechanism for
phenyl cation fragmentation.
Figure 12. Mass spectrum of propylbenzene.
D. Carbonyl Compounds
There are three important fragmentation
pathways for carbonyl containing compounds:
cleavage of bonds on either side of the
carbonyl group (-cleavage),
cleavage of the ,-bond ( -cleavage),
 and (if an alkyl chain of three carbons or more is
attached to the carbonyl carbon) transfer of a -
hydrogen to the carbonyl oxygen followed by alkene
elimination; this rearrangement is one of the few
name reactions in mass spectrometry and is known
as the McLafferty rearrangement.
The most important fragment results from -
cleavage, as this process results in the formation of
a resonance stabilized acylium ion.
 1. Aldehydes
The molecular ion is usually observable,
although it can be of low relative abundance.
The important a- and-patterns (as
well as the McLafferty rearrangement) are
illustrated in Scheme 12.
Scheme 12. Mechanism of fragmentation
for hexanal.
Figure 13. Mass spectrum of hexanal
 2. Ketones
The molecular ion is usually quite abundant.
Fragmentation patterns mimic those of the
aldehydes. It appears that the loss of the larger
alkyl group is favored in ketones in the a-cleavage
process as shown in Scheme 13. This may not be
strictly correct, however, because the abundance of a
fragment ion is a balance of the rates of the reactions
producing it and those causing it to decompose.
For interpretation purposes, the rule that the larger
alkyl group is lost is effective in interpretation.
Scheme 13. Mechanism of fragmentation for
2-pentanone
The complete mass spectrum of 2-pentanone is
given in Figure 14, which illustrates most of
these points. The two ions formed by alpha
cleavage (m/z 43 and 71) then lose CO
(decarbonylate) to give carbocations (with
masses of 15 and 43, respectively). When the alkyl
chains are long, the resulting alkene will fragment
by losses of alkenes and other neutrals (e.g., H2),
Figure 14. Mass spectrum of 2-pentanone
 3. Esters
The molecular ion is usually of low abundance
but generally observable for esters. As in all
carbonyl compounds, a-cleavage is an important
fragmentation process.
In general, cleaving the C-O ester bond occurs
most readily leading to the favorable loss of an
alkoxy radical.
Table 6 summarizes this cleavage process for the
most common types of esters.
 Table 6. Alkoxy Radicals formed from
the most common esters.

Alkoxy Radical
Ester Ion to Observe
Formed
methyl CH3O M - 31
ethyl CH3CH2O M - 45
propyl (and
CH3CH2CH2O M - 59
isopropyl)
phenyl C6H5O (PhO) M - 93
C6H5CH2O
benzyl M - 105
(BzO)
Scheme 15. Mechanism of fragmentation
for methyl butyrate.
Figure 16. Mass spectrum of methyl butyrate
Benzyl and phenyl esters undergo a
rearrangement involving hydride transfer from
the -carbon to the ester oxygen. The resulting
fragments include a neutral ketene and a
charged alcohol as described in Scheme 16
below.
Scheme 16. Most common fragmentation involving
benzyl and phenyl esters.
Figure 17. Mass spectra of benzyl acetate
Figure 17. Mass spectra of phenyl acetate
Benzoate esters tend to lose the alkoxy group
(as a radical) to form an acylium ion (C6H5CO+, m/z
105), which subsequently loses carbon monoxide to
form the phenyl cation (C6H5+, m/z 77). This is
reminiscent of the fragmentation often observed
for aromatic ketones (see Scheme 11 and Figures 12
and 15). An important exception to this pattern
involves benzoate esters bearing alkyl, amino, or
hydroxy substituents at the ortho position.
Proton transfer from the ortho substituent to
the ester oxygen eliminates a neutral alcohol
fragment. This fragmentation is an example of a
proximity effect in organic mass spectra,
specifically an ortho effect. The remaining
aromatic radical cation is often the most abundant
species detected. Illustrations of these two
common pathways are given in Scheme 17 below.
The mass spectra for both methyl benzoate and
methyl 2-aminobenzoate, given in Figure 18, show that
the ortho substituted benzoate ester undergoes a facile
loss of methanol resulting in an abundant M - 32 (m/z
119) ion in the mass spectrum (Figure 18, bottom). Ortho
effects offer one way of distinguishing ortho from meta
and para isomers by mass spectrometry. When this
process cannot occur, the mass spectra of ortho, meta,
and para isomers are usually very similar and nearly
indistinguishable (e.g., o-, m-, and p-ethyl toluene have
nearly identical spectra).
Scheme 17. Most common fragmentation involving
benzoate and ortho substituted benzoate esters.
Figure 18. Mass spectra of methyl
benzoate
Figure 18. Mass spectra of methyl 2-
aminobenzoate
4. Carboxylic Acids
The molecular ion is often of low abundance for
carboxylic acids, but generally observable. As for all
other carbonyl compounds, -cleavage, -cleavage,
and McLafferty rearrangements rule the day. As is
indicated in Scheme 18, the loss of hydroxyl radical
(leading to an M - 17 ion) is indicative of the
presence of the carboxylic acid functionality. All the
important fragmentation events for carboxylic acids
are illustrated in Scheme 18.
Scheme 18. Mechanism of fragmentation for butyric acid
Figure 19. Mass spectrum of butyric acid.
As was seen with esters, benzoic acids
substituted with alkyl, amino, or hydroxy
substituents at the ortho position readily
dehydrate via proton transfer from the ortho
substituent to the hydroxyl group (ortho effect).
Water is lost, resulting in a major M - 18 ion in
the mass spectrum. Scheme 19 outlines this
process for o-toluic acid.
Scheme 19. The ortho effect fragmentation
of o-toluic acid.
Figure 20. Mass spectrum of o-toluic acid.
5. Amides
The molecular ion is usually observable, and will
be a good indication of the presence of an
amide (invoke the nitrogen rule!). An important
fragmentation pattern involves a-cleavage
(breaking either bond to the carbonyl carbon) as
shown in Scheme 20.
Scheme 20. Mechanism of fragmentation for butyramide.
Figure 21. Mass spectrum of butyramide.
6. Anhydrides
Aliphatic acid anhydrides rarely afford a molecular
ion in their mass spectra whereas aromatic
anhydrides usually do. Understanding and
interpreting the mass spectra for anhydrides is
quite straight forward, as they fragment by
following the general rules set forward for all
carbonyl compounds: -cleavage on either side of
the carbonyl carbon contributes to the major ions
observed in the mass spectrum as shown in Scheme
21 for butyric anhydride.
Scheme 21. Mechanism of fragmentation for butyric
anhydride
Figure 22. Mass spectrum of butyric anhydride.
Aromatic anhydrides show evidence of the
molecular ion and undergo a similar
fragmentation as seen for butyric anhydride.
However, an additional rearrangement where
carbon monoxide is lost from the molecule is
evident in nearly all mass spectra of aromatic
anhydrides. The cleavage pattern for benzoic
anhydride is given in Scheme 22.
Scheme 22. Mechanism of fragmentation for benzoic
anhydride
Figure 23. Mass spectrum of benzoic anhydride
It is interesting to note that the ortho effect (as
described above for ortho substituted esters and
carboxylic acids) applies to aromatic anhydrides
as well. The fragmentation for o-toluic
anhydride (given in Scheme 23) is an example of
this general effect.
Scheme 23. Mechanism of fragmentation for o-toluic
anhydride
The mass spectrum of o-toluic anhydride (Figure 24)
indicates the major cleavage pattern outlined above.
Note the presence of the ion due to the loss of o-toluic
acid (m/z 118), and the corresponding absence of that ion
in the spectrum for benzoic anhydride (Figure 23, the ion
would be at m/z 104), and for p-toluic anhydride (Figure
24, bottom, the ion would be at m/z 118).
Another interesting note is the absence of an M - 28
ion (corresponding to the loss of carbon monoxide,
CO) in the spectrum for o-toluic anhydride, and the
presence of that ion in the spectrum for p-toluic
anhydride (at m/z 226). Apparently, the ortho effect
provides for a more facile fragmentation event.
7. Acid Halides
Acid halides afford very low abundance, if not
entirely absent, molecular ions in their mass
spectra. This is true even for aromatic acid
halides. Again, as with all carbonyl
compounds, a-cleavage is a very facile process
with loss of a halogen radical perhaps the most
common event.
Acid chlorides can also lose HCl from the
molecule; this is not a probable event with acid
bromides. Keep in mind that the two common
isotopes for chlorine (35Cl and 37Cl in a 3:1 ratio)
and bromine (79Br and 81Br in a 1:1 ratio) will
lead to the production of M + 2 observed ions in
the spectra. Since the molecular ion is not
abundant, the M + 2 ions are typically very difficult
to ascertain.
Scheme 24. Mechanism of fragmentation for
butyryl chloride.
Figure 25. Mass spectrum of butyryl chloride
E. Other Important Functional
Groups
 1. Alcohols
The molecular ion is usually of very low abundance
or absent for aliphatic alcohols. Just as with carbonyl
compounds, cleavage on either side of the alcohol carbon
(-cleavage) is the most important feature in alcohol
fragmentation. This will typically involve the loss of an
alkyl group, and, often, it is the largest alkyl group that is
preferentially lost. If the alkyl chain attached to the
alcohol carbon is at least of three carbons in length, then
a process similar to McLafferty rearrangements seen for
carbonyl compounds can take place.
Transfer of a -hydrogen to the alcohol oxygen
leads to the loss of water from the molecule.
This dehydration can be a very important
indication for the presence of an alcohol
functionality
Scheme 25. Mechanism of fragmentation
for 2-pentanol.
Figure 26. Mass spectrum of 2-pentanol
Unlike for aliphatic alcohols, the molecular ion
for phenols can be quite abundant. Phenols can
lose the elements of carbon monoxide to give
abundant fragment ions at M - 28, and can also
lose the elements of the formyl radical (HCO)
to give abundant fragment ions at M - 29.
Figure 27. Mass spectrum of phenol
 2. Thiols
The molecular ion is generally more substantial
for thiols than for alcohols. The presence of an
unusually abundant M + 2 ion (4.4% relative
abundance of 34S) is a good indication of the
presence of sulfur, and this can be readily seen in
the spectra of small sulfur-containing compounds.
The mass spectra for thiols mimic closely those for
alcohols. Loss of H2S (analogous to dehydration of
alcohols) is mainly evident in primary thiols.
Just as with alcohols, cleavage on either side of
the thiol carbon (-cleavage) is the most
important feature in thiol fragmentation. This
will typically involve the loss of an alkyl group,
and, often, it is the largest alkyl group that
preferentially fragments.
If the alkyl chain attached to the thiol carbon is
at least of three carbons in length, then a
process similar to McLafferty rearrangements
seen for carbonyl compounds can take place.
Transfer of a -hydrogen to the thiol sulfur leads
to the loss of hydrogen sulfide from the molecule.
This process can be a very important indication for
the presence of the thiol functionality.
Scheme 26. Mechanism of fragmentation for 1-
pentanethiol.
Figure 28. Mass spectrum of 1-pentanethiol.
 3. Ethers
The molecular ion is usually of low abundance,
but of higher abundance than the molecular
ions of alcohols. Important fragments arise from
cleavage of the carbon-oxygen bond (ipso-
cleavage), cleavage of the carbon-carbon bond
adjacent to the oxygen (-cleavage), and transfer of
hydride from the -carbon to the ether oxygen (a
rearrangement of the ion produced from initial a-
cleavage).
Scheme 27. Mechanism of fragmentation for
dibutyl ether.
Figure 29. Mass spectrum of dibutyl ether
 4. Sulfides
The molecular ion is usually of low abundance,
but of higher abundance than the molecular
ions of ethers. Important fragments arise from
cleavage of the carbon-sulfur bond (ipso-
cleavage), cleavage of the carbon-carbon bond
adjacent to the sulfur (-cleavage), and transfer of
hydride from the -carbon to the sulfide sulfur (a
rearrangement of the ion produced from initial -
cleavage).
Scheme 28. Mechanism of fragmentation for dibutyl
sulfide
Figure 30. Mass spectrum of dibutyl sulfide
 5. Amines
The molecular ion is of low abundance or not
detectable. When observable, its odd mass
(when an odd number of nitrogens is present) is
a good indication of the presence of an amine
(nitrogen rule). Important fragments arise from
cleavage of the carbon-carbon or carbon-hydrogen
bond adjacent to the nitrogen (-cleavage), and
hydrogen transfer from the -hydrogen to the
nitrogen.
Scheme 29. Mechanism of fragmentation for
dipropyl amine
Figure 31. Mass spectrum of dipropyl amine
For most amines, ipso-cleavage of the alkyl
group is rarely observed. However, -cleavage of
primary amines leads to the production of an
iminium ion (with formula H2C=NH2+) of m/z 30.
The presence of this ion is very indicative of a
primary amine.
Figure 32. Mass spectrum of propyl amine
 6. Nitriles
The molecular ion is usually of too low an
abundance to be observed. However, the loss of
hydrogen radical (via an -cleavage process) will
almost always produce an observable ion. For
nitriles then, the M - 1 ion is usually more
prominent than the M+. As for the carbonyl
compounds, McLafferty rearrangement involving
transfer of a -hydrogen to the nitrile N occurs
readily for nitriles containing four or more carbons
in an n-alkyl chain.
Scheme 30. Mechanism of fragmentation for
pentanenitrile
The complete mass spectrum of pentanenitrile
is given in Figure 33, which illustrates most of
these points. The other major signals at m/z 55
(loss of ethylene), 54 (loss of ethyl radical), and
43 (propyl cation) result from fragmentation of
the long alkyl chain in this nitrile. The relatively
low abundance ion at m/z 56 is produced by the
loss of HCN from the molecule
Figure 33. Mass spectrum of pentanenitrile
As with most aromatic species, aromatic nitriles
will ionize to give significantly abundant
molecular ions. The mass spectrum of
benzonitrile (given in Figure 34) is a good
example of this phenomenon. The relatively
abundant fragment at m/z 76 arises from loss of
HCN via a rearrangement.
Figure 34. Mass spectrum of benzonitrile
 7. Nitro Compounds
The molecular ion for aliphatic nitro
compounds is seldom observed. The mass
spectrum observed for aliphatic nitro
compounds is usually due to the fragmentation
of the alkyl portion of the molecule.
However, there are two fragment ions that are
indicative of the nitro group: one is NO+ ion (m/z
30), and another is the NO2+ ion (m/z 46).
Figure 35. Mass spectrum of 1-nitrobutane
 8. Halogenated Compounds
The molecular ion for alkyl halides ranges
from observable for alkyl iodides to barely
detectable for alkyl fluorides. Because of the
isotope ratios for chlorine and bromine, the M+
and M + 2 observed ions are quite clear and
indicate the presence of these elements.
The most important fragmentation process for
the heavier alkyl halides (bromine and iodine)
involves simply losing the halogen to form an
alkyl carbocation (ipso-cleavage). For this
reason, the mass spectra for these halogenated
compounds will be dominated by the
fragmentation of an alkyl ion and, thus, mimic
the mass spectra of simple alkanes.
Competing with this loss (for sufficiently long
chain primary halides) is a cleavage (e.g., the
loss of an ethyl group in the fragmentation of 1-
bromohexane (to give ions of m/z 135/137) and
1-chlorohexane (to give ions of m/z 91/93))
(see Scheme 31 and Figures 37 and 38). The
product ions are 5-membered ring halonium
ions.
Scheme 31. Mechanism of fragmentation for 1-
bromohexane
For the lighter halogens (fluorine and chlorine)
the loss of hydrogen halide is important
particularly when a 1,3 or 1,4-elimination is
possible. In the cases of 1-chlorohexane and 1-
fluorohexane, the product from loss of HCl (or
HF) is the product ion of m/z 84 (see Scheme 32
and Figures 38 and 39).
Scheme 32. Mechanism of fragmentation for 1-
chlorohexane
Figure 36. Mass spectra of 1-iodohexane
Figure 37. Mass spectra of 1-bromohexane
Figure 38. Mass spectra of 1-chlorohexane
Figure 39. Mass spectra of 1-fluorohexane