Download I 14-7 ION CHEMISTRY

Chapter 14 I Fragmentation and Ion Chemistry
421
14-7 ION CHEMISTRY
14-7a
Unimolecular Fragmentation
Kinetics. The use of mass spectrometry as a structural tool (as opposed to its
use simply for molecular weight measurements) primarily depends on observation of
the unimolecular fragmentations that excited ions undergo. In this section, the principles that underlie ionic reactions in the isolated phase environment are discussed. The
controlling factors are the distribution of internal energies the ions possess and the
thermochemistry of the dissociation processes available to them.
Time Scale of Fragmentation. The mass spectrometer time scale is illustrated
in Figure 14-26. Note that longer time scales apply to quadrupole instruments than
magnetic sectors, and that quadrupole ion traps and ICR instruments access extremely
long times. The mass spectrum is a time-integrated picture of all reactions occurring
after ionization and before ions leave the source. Although this length of time is as short
6
as ~ 10- s, it is long compared with bond vibrational periods of 10- 10 to 10- 12 s. In almost
all excited ions, fragmentation does not occur within a vibrational period; rather, internal energy is shuttled around the excited, isolated ion until it collects in the appropriate
modes for fragmentation to occur. The rate at which fragmentation occurs increases
rapidly with excess internal energy above the activation energy. This characteristic is
the main reason why thermochemistry controls mass spectrometric fragmentation
behavior.
Potential Energy Surfaces. Unimolecular fragmentations are normally
endothermic reactions and, even when exothermic, they often have substantial activation energies. Potential energy surfaces are shown schematically in Figure 14-27 for the
two main types of unimolecular reactions. These are simple bond cleavages, which have
small or no reverse activation energies, and those fragmentations that involve rearrangement of bonds and in which reverse activation energies can be substantial. Note
that rearrangements must have low activation energies to compete with simple bond
cleavages since they have substantial entropic requirements, which limit reaction rates.
Therefore, rearrangements tend to be favored for ions of low internal energy, for example ions generated by soft ionization methods or by low energy EI, or for ions examined
at long intervals after ionization when only low internal energy ions survive. Relatively
little energy in excess of the activation energy for fragmentation is required to observe
products of simple cleavage on the time scale of the mass spectrometer. The additional
energy required for rearrangement fragmentation to proceed at an observable rate can
be substantial. The different forms of the rate curves associated with these reaction
types are illustrated in the lower half of Figure 14-27. Note how the rate constants
depend on internal energy for (1) simple cleavage and (2) a rearrangement process.
However, the important, practical conclusion is that only when rearrangements have
substantially lower activation energies can they compete with simple cleavages, because
of the greater excess energy required to cause observable fragmentation on the time
-
Ion ChemistryOccurs
=
=
.s::"
=
......
=
;:::
Figure 14-26
Time scale for El and Cl (seconds).
Part IV I Mass Spectrometry
422
AB•+c·
>-
(a)
>.
....
Q)
Cl
w
c
w
-
c·.;:::
....
Cl
Q)
c
- ~·
.2
c
c
Q)
Q)
0
fr.
0..
Reaction Coordinate
Ase·+
Reaction Coordinate
(b)
Excess
Energy-
Excess
Energy
Figure 14-27 Potential energy surfaces and energy dependence of
uni molecular dissociation, showing typical simple bond cleavage (a}
and rearrangement (b}. £ is internal energy and k(£} is reaction rate
constant.
scale of the mass spectrometer. The lower part of Figure 14-27 illustrates competition
between rearrangement and simple cleavage reactions and shows that the former only
compete if they have low activation energies and if the ions examined are of low internal energy. Figure 14-31 illustrates the point just made by showing how rearrangements
can be favored by simply lowering the energy deposition in EL
Internal Energy Distributions P(£). Ions are generated with a distribution of
internal energies on electron ionization. Transfer of the full kinetic energy of the electron to the molecule is unlikely; the amount of energy transferred depends on the
nature of each individual electron-molecule collision. When a population of molecular
ions is considered, there is an associated distribution of ion internal energies, termed
P(E) (Figure 14-28). Since electron ionization is usually achieved under high vacuum,
i.e., collision-free conditions, the distribution of internal energies of molecular ions M+·
is not altered by collision and it certainly is not a Boltzmann distribution. The shape of
the distribution associated with electron impact depends on the probability of excitation to various excited states of the ion. It ca11 be controlled to some extent by varying
the ionizing electron energy, since the maximu'tn energy the ion M+· can have is the difference between the electron energy and the minimum energy required for ionization,
namely, the ionization energy.
/
rMolecular ions (Those of low energy are stable
to spontaneous dissociation)
Excited
Neutrals /
/
,,,/"-
--
__
0
-IE-
(70-IE)eV
E (eV)
Figure 14-28 Stylized internal energy distribution P(£} resulting from
impact by electrons of 70 eV kinetic energy on an organic molecule.
The maximum internal energy that an ion can acquire is 70 eV, minus
the ionization energy (IE}. Most ions acquire small internal energies.
Chapter 14 I Fragmentation and Ion Chemistry
423
The internal energy distribution P(e,) is important because it controls the subsequent unimolecular dissociation behavior of the ion population, just as the temperature
of a system with a Boltzmann distribution of internal energies controls its chemistry:
Thermochemical Control. Fragmentation behavior of isolated ions is controlled by the thermochemical factors (activation energies) already discussed as well as
by the kinetic factors just discussed. These can be considered together to produce a
breakdown curve. Such a curve shows the dependence of the fragmentation behavior
on the internal energy. For example, ionized 1-propanol molecular ion undergoes H·
loss to give mlz 59 as the lowest energy process, only to be replaced in turn by higher
energy consecutive fragmentations, yielding m/z 31 and 29. The breakdown curve
demonstrates the behavior of molecular ions with particular internal energies. For
example, ions that have exactly 4.4 e V of internal energy yield 96 % of 31 + and 4 % of
59+. Such ions can be generated by charge exchange with N2+· reagent (IE= 15.6 e V, IE
[propanol] = 10.2 e V, difference 4.4 eV).
A mass spectrum is simply a breakdown curve with appropriate weighting of the
internal energy axis. In other words, depending on the method and conditions of ionization, ions have a particular internal energy distribution P(c). By convoluting this distribution with the breakdown curve, the mass spectrum is obtained (Figure 14-29). This
figure, which should be studied carefully, illustrates how different methods of generating a set of molecular ions result in different unimolecular product distributions, that is,
different mass spectra.
Fragmentation occurs unimolecularly for ions whose internal energy £ equals or
exceeds a minimum value, £ 0 , the activation energy for fragmentation. Ions with less
Q)
(.)
c
c
c
"C
::J
..0
c::(
50
§?
:;::
c
a;
a::
2
4
6
8
10
E (eV)
FI
~'~
EI (Low Energy)
2eV
€
SeV
Q)
(.)
~
~
59 60
c
c
"C
Q)
(.)
"C
..0
c::(
..0
c::(
Q)
>
"+:
.5:!
Q)
a::
31
c
c
c
c
::J
::J
31
Q)
>
:;:
m/z
4.2eV
€
i
~
~
CE (N 2 Reage t)
'
0
~
60
59
Q)
(.)
c
c
31
"C
c
::J
..0
<(
29
Q)
>
c
a;
a::
€
m/z
c
Q)
a::
59
m/z
Figure 14-29 Convolution of the breakdown curve (top, an intrinsic
property) with the internal energy distribution (Pfc]) resulting from
different ionization techniques under particular experimental conditions to produce mass spectra of 1-propanol. Fl indicates field ionization, a soft ionization method used for vapor phase samples.
Part IV I Mass Spectrometry
424
A••s
>-
Cl
....
Q)
(a)
c:
w
(b)
0
These ions
ore stable
:g
.0
0
These ions have
necessary energy
to fragment
.....
c:
CL
Q)
;£
€=€0
Reaction Coordinate
Internal Energy (E)
Figure 14-30 (a} Thermochemical quantities that control unimolecular dissociation and (b} their effects on the internal energy distribution P(E}.
than this internal energy are stable indefinitely, whereas those with greater energies
fragment at a rate that rapidly increases with energy in excess of the activation energy.
As discussed previously, vertical electronic transitions can convert neutral molecules
into molecular ions with a range of internal energy states (Section 13-3). In some collisions the minimum energy required to cause ionization, the ionization energy IE, is
transferred to the molecule. This situation leads to formation of the ion AB+· in its
ground state, with zero internal energy. In other collision events the energy transferred
might exceed the minimum energy required to cause ionic dissociation, namely, the
appearance energy AE. Figure 14-30 illustrates these quantities in addition to their difference, the activation energy, £ 0 ( =AE- IE). Both the potential energy surfaces and the
internal energy distribution of the ionic population are shown. In this figure, it is possible to divide the internal energy distribution into two regions, based on whether the initially formed ions have or do not have sufficient energy to fragment unimolecularly.
This division provides an indication of the molecular ion abundance relative to fragment ion abundances recorded in the mass spectrum.
Consider the behavior of acetophenone on electron ionization. Energetic electrons interact with the vapor phase molecules producing the molecular ion as a result
of electronic transitions (Figure 14-30a). In a few cases, the minimum energy required
for ionization, or the ionization energy, may be delivered to the molecules giving molecular ions in their ground electronic and vibrational states. In many more cases, each
molecular ion has a particular excess internal energy £, and the population has an
energy distribution P( £) (Figure 14-30b ). The more highly excited ions rapidly fragment
to give ionic fragments that are excited and can fragment further. Ions of lower energy
may fragment but by different routes: the favored fragmentation mode depends on the
degree of internal excitation of each ion. A network of competing and consecutive unimolecular reactions exists and leads to a set of products that evolves with time. The
mass spectrum is simply a sampling of this product distribution at a particular time after
ionization, often a time of about 1 µs.
The main electron impact chemistry of acetophenone is shown in eq. 14-56 with
EI chemistry:
e-
M-
M+· -
m/z 120
(M-CH3)+-c6H/ -
mlz 105
mlz 77
C4H 3+
mlz 51
Chemical species:
0
11
C H CCH 3 6
5
0
(14-56)
11
(C6H 5 CCH3)+· -
C 6H 5C-0+ -
C6H/ -
C4H 3+
Energy requirements:
OeV
9eV
lOeV
e0
=
1 eV
13 eV
e0 =4eV
16 eV
E
0
=7eV
Chapter 14 I Fragmentation and Ion Chemistry
425
70 eV EI
15 eV EI
Emax= 6eV
€max= 70- IE= 61 eV
€max=15-IE =6eV
Q)
Q)
0
0
c:
c:
c
c
-g
"O
c:
:::>
::::J
.0
~
.0
-
.~
~
Q)
Q)
.~
c
w
a::
+-
'------'-~~-'-~~-'---'-~~
m/z
c
~'--~~~~~-'-~~'-------''---~
m/z
Figure 14-31 Thermochemical factors control El mass spectrum of
acetophenone.
the energy requirements for each product referenced to the neutral molecule. A linear sequence of reactions is involved in this particular molecule. If one assumes that
a fragment ion is generated from all ions that have sufficient energy to make this reaction accessible, then the mass spectrum can be inferred from a knowledge of the
molecular ion internal energy distribution P(c) and the thermochemistry of fragmentation. To a first approximation, the mass spectrum is determined by such thermochemical factors. Figure 14-31 illustrates this principle for acetophenone. For example, all molecular ions with internal energies between 1 e V (the onset of 105+
formation) and 4 e V (the onset of 77+ formation) ca:n be assigned as fragmenting to
yield stable 105+ ions. The ion abundance in the mass spectrum is taken simply as this
area in the P(c) distribution. Figure 14-31 also shows the increase in molecular ion
abundance as the ionizing electron energy is reduced. The practical advantage of this
relative increase in molecular ion abundance is offset by a decrease in ionization efficiency. Those molecular ions in the distribution P(c) that are generated with insufficient internal energy to surmount the barrier for even the lowest energy fragmentation process must appear in the mass spectrum as molecular ions. Those with greater
internal energies fragment.
Acetophenone behaves straightforwardly because competitive processes are not
important in the breakdown pattern. All molecular ions of energy 1 to 4 e V behave the
same way and lose CH3 · to give benzoyl fragment ions of mass 105. When competitive
reactions are possible, it is still often true that thermochemical factors dominate and
only the lowest energy processes available to a given ion are observed.
The control of thermochemistry over the type and degree of fragmentation can be
illustrated by considering a set of monosubstituted benzenes, each of which undergoes
a simple cleavage reaction as its main fragmentation pathway. Table 14-4 is a collection
of this thermochemical data and illustrates how the abundance of the fragment ion
increases with decreasing activation energy (£0). If the molecular ions of all these compounds have roughly similar internal energy distributions, this inverse dependence of
ion abundance on £ 0 is exactly the behavior expected from a consideration of Figure
14-30. Summarizing this approach, if one knows (1) the energy requirements for fragmentation and (2) the internal energy distribution P(c), one can approximate the mass
spectrum without considering the kinetics of individual reactions. This approximate
thermochemical approach to mass spectra works best when complex rearrangements are
not important.
Similar considerations apply to CI and other ionization methods.
Part IV I Mass Spectrometry
426
TABLE 14-4
Thermochemical Control of Fragmentation of Substituted Benzenes*
Substituent
Neutral
Fragment
COCH 3
C(CH 3 ) 3
(CO)OCH 3
CzH5
N0 2
CH 3
CH 3
CH 3
OCH 3
CH 3
N0 2
H
I
I
Br
Cl
Br
Cl
IE (eV)
AE (eV)
9.3
8.7
9.3
8.8
9.9
8.8
8.7
9.0
9.1
10.0
10.3
10.8
11.3
12.2
11.8
11.5
12.0
13.2
£0
(eV)
0.7
1.6
1.5
2.5
2.3
3.0
2.8
3.0
4.1
Fragment
lons/M+t
2.2
2.1
1.5
1.0
0.7
0.5
0.4
0.4
0.2
*Table adapted from I. Howe and D.H. Williams, Principles of Organic Mass Spectrometry, McGraw-Hill Book
Co., New York, 1972.
t Ratio of fragment to molecular ion abundance, 70 eV El.
14-7b
Ion-Molecule Reactions
Ion-molecule reactions occur in the course of ionization by all methods, except EI. They
can be used as an alternative to fragmentation, to elucidate molecular structures. The
subject of gas phase ion chemistry, which includes the study of ion-molecule reactions,
is important both for the information it yields on solution chemistry through characterization of analogous processes occurring in the absence of solvent, as well as for its
intrinsic interest. Gas phase acidities and basicities, as well as other types of reactivities,
often show more systematic trends than do the corresponding solution properties. An
early arid well-known example is the order of basicity of primary, secondary, and tertiary amines, which increases in this simple sequence in the gas phase but not in solution where solvent effects lead to the order tertiary > primary> secondary. By studying
ion-molecule reactions in the gas phase, one is studying systems in the same state as
examined in ab initio calculations.
Potential Energy Surfaces. A key to gas phase ion chemistry is that gaseous
ions have high enthalpies and are stabilized by interaction with any molecule. Polarization stabilizes the charge, and ion-molecule association complexes are normally
more stable than the free reagents. However, if the collision complex does not have
an available reaction channel, it will revert to reactants if excess energy is not
removed, usually by collision with a third body. The very different forms of the potential energy surfaces for the same ion-molecule reaction in solution and in the gas
phase are illustrated in Figure 14-32. The differences are entirely due to solvent
effects. In solution the ionic reagent (AB+) is already stabilized by solvation, but its
gas phase counterpart is not. Hence the interaction with C is strongly stabilizing in the
>-
i;: Reactants
i
c
AB•+c
CJI
L..
----
Q)
c
Gas Phase
Products
A++sc
UJ
0
'EQ)
UJ
0
:;::
Reactants
AB++c
c
Q)
+-
&
0
0..
Reaction Coordinate
Reaction Coordinate
Figure 14-32 Potential energy surfaces for ion-molecule reactions
in the gas phase and in solution.
Chapter 14 I Fragmentation and Ion Chemistry
427
latter but not the former case. In both systems the structural changes necessary to
achieve the activated complex configuration are endothermic with respect to the surrounding regions of the potential energy surface. Large energy changes occur across
the gas phase reaction surface because energy differences between unsolvated and
monosolvated ions are large.
Rates of Ion-Molecule Reactions. Although important exceptions exist, many
exothermic ion-molecule reactions occur on every collision. In other words, they proceed without an activation barrier, as already shown in the potential energy surfaces
illustrated in Figure 14-32. Ion-dipole attractive forces increase the rate of approach of
the ion and neutral molecule and this makes ion-molecule reaction rates even greater
than typical collision rates among neutral molecules. The rates of the reactions are
therefore very high, 10- 9 cm3 molecule- 1 s- 1 (6 x 1011 liter mo1-1 s- 1).
Structural Elucidation Using Ion-Molecule Reactions. Instead of employing
unimolecular fragmentation, it is possible to obtain structural information through a
study of reactions with structurally diagnostic ions. Despite its obviousness-given the
analogy with solution reactions-this approach has seen relatively little application.
Ion-molecule reactions are used to generate characteristic ions from the analytes of
interest in CI, DI, and SI, as described in Section 13-30. Nevertheless, even in these
cases, structural information still arises predominantly from the unimolecular dissociation of the ion-molecule reaction product. This situation occurs partly because the ion
population is not at thermal equilibrium in most mass spectrometers, and hence the
effects of internal energies on ion-molecule reactions may exceed the structural effects
of interest. Nevertheless, it is possible to perform gentle ion-molecule reactions that are
chemically finely controlled in the mass spectrometer. Not only are the reactions analogous in type to those seen in solution (acid-base reactions, nucleophilic substitution,
cycloaddition) but also high degrees of regio-, stereo-, and even enantioselectivity can
be achieved.
Although ion-molecule reactions can be studied in the ion source of a single stage
mass spectrometer, MS-MS techniques are normally used since this approach allows
definition of the nature of both the ionic and the neutral reactant. An example of
bimolecular ionic chemistry applied to structural identification is found by considering
gas phase Diels-Alder reactions (eq. 14-57).
[4+2]+
--~
~--
(14-57)
CID
mlz 43
+
C~=C=OH
14-8
+
~
14-9
mlz 97
The above reaction has been used to distinguish three isomeric C2H 3 0+ ions
(14-7 to 14-9). When reacting with isoprene, the acetyl cation (CH 3 CO+) is unique in
that it displays a [4+2+] Diels-Alder cycloaddition product (eq. 14-57), whereas the
other isomers undergo proton-transfer reactions. Further distinction of C2H 30+ isomers is achieved in reactions with methyl anisoles. The acetyl ion preferentially forms
the intact adduct ion, whereas the other isomers fail to do so, their spectra being dominated by characteristic charge-exchange, proton-transfer, and adduct-fragmentation
products.
Enantioselectivity is shown in gas phase ion-molecule reactions and can be used
to distinguish optical isomers. Chiral reagents show different reactivity towards enantiomers. An example is the measurement of equilibrium constants for reactions involving transfer of the R- and S-enantiomers of a-(1-naphthyl)ethylammonium (NapEt+)
cation between (S,S)-dimethyldiketopyridino-18-crown- 6 (S,S-14-10) and the achiral
host 18-crown-6 (eq.14-58).
Part IV I Mass Spectrometry
428
~
H 3N
14-10
(S,S-14-lO)·(R or S)-NapEt+ + 18-Crown-6 -
ac-(1-naphthyl)ethylammonium cation
(S,S-14-10) +18-Crown-6·(R or S)-NapEt+
(14-58)
The equilibrium constants are 567 ::±:: 68 and 130 ::±:: 15 for the reactions involving
S- NapEt+ and R- NapEt+ ,respectively. It is now feasible, in many cases, to distinguish
enantiomers using mass spectrometric methods.
Ion-Molecule Reactions Accompanying Ionization (Cl, DI, and SI). One of
the principal advantages of EI in chemical analysis is the absence of ion-molecule reactions, a feature that accounts for the highly reproducible nature of EI mass spectra. The
fact that ion-molecule reactions may occur in all of the other major types of ionization
methods deserves emphasis. Consider, for example, the electron attachment CI mass
spectrum of tetrachloronaphthalene, shown in Figure 13-9. As noted previously, the
molecular anion (M-·) is readily recognized in this mass spectrum; however, under
some conditions there is an abundant set of ions that lie 19 Da below the molecular
anion (that is, the all 35 Cl-version of this isotopic cluster is at mlz 243 compared with m/z
262 in the molecular ion). The isotopic cluster, mlz 243, 245, 247 clearly suggests a
trichloro ion, yet the mass difference of just 19 Da is inconsistent with this conclusion.
In fact, an ion-molecule reaction must occur, and it has been shown that hydroxylation
is possible when CI mass spectra are recorded. The chemistry involves chloride displacement by hydroxide, which is shown in eq. 14-59. It is interesting to note that an
~::
Cl
~(~H~ ~o
~Cl
~Cl
Cl
(14-59)
Cl
even closer examination of this same CI mass spectrum reveals the occurrence of other
ion-molecule reaction products. Low-abundance ions are centered at m/z 279 and mlz
299, which result from hydroxylation and chlorination of tetrachloronaphthalene, as
illustrated by the reactions in eq. 14-60. Such features do not normally make a major
Cl
Cl
o¢c::
Cl
Cl
+X =OH- or Cl-
x
(14-60)
Cl
Cl
contribution to CI mass spectra run under conditions where analytical information is
sought. The chlorine substitution process is a prominent exception.
Intact cations can be generated by any of a variety of DI and SI methods and
delivered into the gas phase with high efficiency as preformed ions. These ions possess
different amounts of internal energy and dissociate to different extents, depending on
the amount of energy deposited during ionization. For example, when choline chloride
is examined from a glycerol matrix by energetic Xe atom bombardment (FAB), the
spectrum is dominated by the intact cation, m/z 104. However, if the solid material is
Chapter 14 I Fragmentation and Ion Chemistry
429
examined directly without using a diluting matrix, either by laser desorption or by energetic ion impact (SIMS), then the intact cation c+ is accompanied by a higher homologue. This product is due to ion-molecule reactions in the energized selvedge. Mechanistic studies using isotopic labeling have established that the process involves
intermolecular transalkylation.
14-7c Advanced Ion Chemistry
Gas phase ion chemistry is extremely rich in terms of the variety of structures encountered and the reactivity displayed, and it is relatively easily accessible experimentally.
In this treatment of mass spectrometry, we have rationalized the processes observed
rather than enquiring deeply into the underlying physical and chemical principles. This
short section briefly highlights ion chemistry in the hope that some students will be
intrigued. Liturature references are given for further information.
Fragmentation Accompanied by Rearrangement. Fragmentation tends to
occur at particular bonds that correspond to the formation of energetically favored products. Thus the 2-alkyl substituted pyridines (but not the 3- or 4-substituted isomers)
undergo facile 8-C-C cleavage in EI to give the cyclic product ion shown in eq.14-61.
+ R'
(14-61)
A similar case is the fragmentation of the alkaloid candicine, the DI spectrum and
fragmentation mechanism of which is shown in Figure 14-25. Note that the neutral
molecule lost is very stable, and the ion is resonance stabilized.
Regioselectivity. Reactions of gas phase ions possess the same possibilities for
stereo- and regiocontrol that exist in solution. Much work is being done in this area and
it can be briefly illustrated by considering the regioselectivity of deprotonation of sulfones, which has been investigated by negative ion chemical ionization. In principle, the
deprotonation of asymmetric sulfones can result in a mixture of different a-sulfonyl
carbanions, as exemplified in eq. 14-62 for methyl-d3 isopropyl sulfone. With this analyte a moderate preference for the formation of the primary [M- DJ- carbanion is
(14-62)
observed, thus indicating a slightly higher stability of the anion.* On the other hand, the
deprotonation of benzyl methyl-d3 sulfone proceeds by proton abstraction from the
benzylic position.
In cases where an ion-molecule reaction proceeds to generate a chiral center, the
least hindered face is normally the site of attack, as expected. For example, axial orientation of the new C- H bond in 4-tert-butylcyclohexanone is strongly favored on
reduction using a pentacoordinate silicon hydride reagent. By contrast, 3,3,5-trimethyl-
*T. Surig and H.F. Grutzmacher, Org. Mass Spectrom., 24, 851 (1989).
a
Part IV I Mass Spectrometry
430
cyclohexanone shows almost exclusive equatorial hydride attack, the axial face being
blocked by the axial methyl at C-3 (eq.14-63)*
H
0
+H-
CH 3
I
CH3-1~
CH3
-----
CH 3
I
CH3-1~
CH3
H
H
99%
o-
0
H
~c
Axial-H (
CH 3
H
+H-
-----
14-63
)
H
CH3
RC
0
CH3
91%
Equatorial-H
Otherwise Inaccessible Neutral Molecules. Mass spectrometric methods
provide access to many hypervalent, energy-rich, or previously unknown neutral compounds. Some of these compounds are remarkably simple, including HNC, H 2 CC1H,
CH3C(OH)=CH2 , H 2Cl, CH30H2 , and RNH3 , all prepared from the corresponding
ions by neutralization of the fast beam. These compounds were shown to be stable by
using the neutralization-reionization technique, an experimental tool in which ions are
neutralized by charge exchange and then reionized. An intact reionized signal indicates
that the corresponding neutral species is a stable compound. In the case of ethylenedione, a beam of ions of structure [O=C=C=O]+·, was generated either by CI of
carbon monoxide or by dissociative electron impact on squaric acid. This species was
neutralized by charge exchange with xenon. Several microseconds later, the neutral
beam was reionized by collision with oxygen. The fact that an intact ion was observed
at mlz 56 demonstrates that the neutral O=C=C=O is stable.t
In related experiments, the neutral fragments of dissociation are separated from
the ionic constituents of the beam and then ionized by charge exchange and characterized by their fragmentation behavior. An instructive case is the neutral fragment generated when the molecular ion of methyl acetate dissociates by ex-cleavage in one of its
principal pathways, to yield the acetyl cation, m/z 43. The expected neutral fragment, the
methoxyl radical (CH3 0") is generated but is accompanied by an isomer, the hydroxymethyl radical (HOCH2"), which is more stable by about 42 kJ mo1- 1 (10 kcal/mol- 1).+
Ion-Neutral Complexes. Some fragmentation processes proceed through ionneutral complexes in the exit channel of the potential energy surface. These loosely
bound complexes survive for long enough to allow rearrangement and exchange of
groups between the ionic and neutral components. This is one way in which rearrangements occur in the course of ionic fragmentations. Note that the ion-neutral complexes
are similar to the ion-molecule complexes produced in the course of ion-molecule reactions (Figure 14-32). Ion-neutral intermediates in fragmentation, therefore, provide an
important bridge between the two main processes in ion chemistry, unimolecular dissociation and ion-molecule reactions. Loss of the stable neutral molecule CHzO by oxonium ions to yield carbenium ions proceeds through an ion-neutral complex (eq.14-64).
Isomerization of the carbenium ion R + can occur in the course of this apparently simple bond cleavage, for example, n-RCO+ yields sec-R +. Other examples include H/D
*Y. Ho and R.R. Squires, J. Am. Chem. Soc., 114, 10961 (1992).
tD. Siilzle, T. Wieske, and H. Schwarz, Int. J. Mass Spectrom. Ion Proc., 125, 75 (1993).
•J.K. Terlouw and H. Schwarz, Angew. Chem. Int. Ed. Engl., 26, 811 (1987).
Chapter 14 I Fragmentation and Ion Chemistry
431
(14-64)
exchange in ion-molecule reactions. The extent of exchange in such reactions depends
on the depth of the potential well.*
Dissociation of Multiply Charged Ions. With the advent of electrospray mass
spectrometry, the dissociation of multiply charged ions has become of practical interest.
The major difference between singly and multiply charged ions is the release of coulombic energy on dissociation. The expectation that multiply charged ion dissociation is
facilitated has been confirmed in studies of peptides. The charges are seldom closer than
0.5 nm apart, but the coulombic energy associated with two charges separated by this
1
amount is 278 kJ mo1- (66.5 kcal mol- 1)! This large amount of energy assists in dissociation, but short-range chemical bonding forces are stronger than the coulombic forces so
that the ions are metastable to dissociation and can live indefinitely. (The coulombic
1
energy [kJ mol- ] = 138.8/r[nm].) When fragmentation does occur, the coulombic
energy appears, at least in part, as kinetic energy of separation of the two fragments.
From this energy the distances between the two charges in the fragmenting ion can be
estimated. For example, the ion C6H 62 + isomerizes to the charge-separated form
H 3 C-+c=c=c=c+-cH3 , which fragments to give CH3 +and C H +accompanied
5 3
by a kinetic energy release of 2.6 e V, which is consistent with an intercharge distance of
0.55 nm. This value is consistent with the expected bond lengths in the linear ion. t
Analogies With Solution Chemistry. Many mass spectrometric reactions display analogies with solution reactions, whereas in other cases there are sharp differences due to the effects of solvent in the solution case. For example, the Fischer indole
synthesis can be performed in the chemical ionization source of a mass spectrometer
and it proceeds by deamination of the protonated hydrazone, exactly as in solution. Eq.
14-65 shows the Fischer indole synthesis in a CI source, when a mixture of phenylhy-
6NH'+
I
CH -C-CH
3
3
o:w
H 3 C""- _,.,...CH3
0
~
N
H
H2 C~ _,.,...CH3
~
/+NH
(){T
,CNH2 +
)
N
c o - C H3
+
N
H2
+-
((H
\2
+I
N
H2
(1'-'c/CH;
H~
m/z 149
c
_,.,...CH3
""'NH
m/z 132
+2
H C!fi
II
N NH
H + 2
o:CH,
(14-65)
~
2Jl_,.,...CH3
. (NH
N
H2
+
2
drazine and acetone are introduced. Product analysis is by isolation of the protonated
hydrazone (m/z 149) and its characterization by collision with nitrogen (MS-MS). The
major process is loss of 17 Da (NH3) from the protonated hydrazone. These observations confirm the mechanism and its similarity to the solution process.+
*T.H Morton, Tetrahedron, 38, 3195 (1982).
1R.G. Cooks, J.H. Beynon, R.M. Caprioli, and G.R. Lester, Metastable Ions, Elsevier, Amsterdam (1973).
*G.L. Glish, R.G. Cooks, J. Amer. Chem. Soc., 100, 6720 (1978).