Gas-phase fragmentation of deprotonated p-hydroxyphenacyl derivatives

Article abstract of DOI:10.1021/jo1025223

Electrospray ionization of methanolic solutions of p-hydroxyphenacyl derivatives HO-C₆H₄-C(O)-CH₂-X (X = leaving group) provides abundant signals for the deprotonated species which are assigned to the corresponding phenolate anions ^-O-C₆H ₄-C(O)-CH₂-X. Upon collisional activation in the gas phase, these anions inter alia undergo loss of a neutral "C ₈H₆O₂" species concomitant with formation of the corresponding anions X^-. The energies required for the loss of the neutral roughly correlate with the gas phase acidities of the conjugate acids (HX). Extensive theoretical studies performed for X = CF₃COO in order to reveal the energetically most favorable pathway for the formation of neutral "C₈H₆O₂" suggest three different routes of similar energy demands, involving a spirocyclopropanone, epoxide formation, and a diradical, respectively.

Full text of DOI:10.1021/jo1025223

ARTICLE
pubs.acs.org/joc
Gas-Phase Fragmentation of Deprotonated p-Hydroxyphenacyl
Derivatives
Marek Remeꢀs,†,‡ Jana Roithovꢁa,*,† Detlef Schr€oder,*,‡ Elizabeth D. Cope,§ Chamani Perera,§
Sanjeewa N. Senadheera,§ Kenneth Stensrud,§ Chi-cheng Ma,§ and Richard S. Givens§
†Department of Organic Chemistry, Faculty of Sciences, Charles University in Prague, Hlavova 8, 12083 Prague 2, Czech Republic
‡Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nꢁamꢀestí 2, 16610 Prague 6,
Czech Republic
§Department of Chemistry, University of Kansas, Lawrence, Kansas 66045, United States
S Supporting Information
b
ABSTRACT: Electrospray ionization of methanolic solutions of p-
hydroxyphenacyl derivatives HO-C6H4-C(O)-CH2-X (X = leaving
group) provides abundant signals for the deprotonated species which
are assigned to the corresponding phenolate anions -O-C6H4-C(O)-
CH2-X. Upon collisional activation in the gas phase, these anions inter
alia undergo loss of a neutral “C8H6O2” species concomitant with
formation of the corresponding anions X-. The energies required for
the loss of the neutral roughly correlate with the gas phase acidities of
the conjugate acids (HX). Extensive theoretical studies performed for X
= CF3COO in order to reveal the energetically most favorable pathway
for the formation of neutral “C8H6O2” suggest three different routes of
similar energy demands, involving a spirocyclopropanone, epoxide
formation, and a diradical, respectively.
’ INTRODUCTION
in the photocleavage of the title compounds in solution, whereas
the gaseous ions investigated below are unsolvated. Notwith-
standing these differences, the gas-phase experiments can allow
for the determination of the intrinsic reaction mechanism as well
as their energetics and to directly compare these with theoretical
results.8 Our original intention was actually to explore the gas-
phase chemistry of the ionized compounds (either cations or
anions) in order to find a suitable system for probing the
Favorskii-type photochemistry that occurs in solution in a
“gas-phase photochemical experiment”.9 It was found, however,
that simple deprotonation to the corresponding phenolate ion
and their subsequent collision-induced fragmentation reactions
bear an analogy with the formal Favorskii-type process observed
in solution-phase photolysis. Furthermore, regardless of their
possible relevance to condensed-phase processes, the fragment-
ations of the phenolate anions are of interest on their own.
p-Hydroxyphenacyl derivatives HO-C6H4-C(O)-CH2-X (1)
bearing a suitable leaving group X undergo an efficient photo-
reaction in water to yield the phenylacetic acid (2) via initial
formation of a biradical (3), followed by ring closure to a
cyclopropanone (4), and subsequent hydrolysis to 2. Overall,
the sequence 1 f 2 corresponds to a photo-Favorskii rearrange-
ment. A competing reaction, the decarbonylation to the quino-
methane 5, also takes place, followed by hydration to yield the
corresponding p-hydroxybenzyl alcohol 6 (Scheme 1).1
Owing to its high photoefficiency and compatibility with
aqueous solvents, the reaction is of potential interest for the
photorelease of compounds for medical or biological purposes2
and has therefore been the subject of intense research in the last
years.3,4 While transient absorption spectroscopy has provided
deep insight into the photochemical reaction,1-4 the precise
mechanism of the complex rearrangement is still a matter of
debate.5
’ RESULTS AND DISCUSSION
Herein, we report the results of some mass spectrometric
experiments which deal with free -O-C6H4-C(O)-CH2-X ions in
the gas phase.6,7 Consideration of the unsolvated ion represents,
of course, a major change when comparison is made with
condensed-phase chemistry in many respects. Moreover, in the
studies described below we use collisional heating, rather than
the photoexcitation applied in Scheme 1. Most important in the
specific context is that water has been shown to play a critical role
Upon collision-induced dissociation (CID) of the mass-
selected ions in an ion-trap mass spectrometer, each of the
p-hydroxyphenacyl derivatives studied that bears a reasonably
good anionic leaving group showed dissociation according to
reaction 1.
Received: December 28, 2010
Published: March 08, 2011
r
2011 American Chemical Society
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ARTICLE
Scheme 1. Photoinduced Favorskii Rearrangement of p-Hydroxyphenacyl Derivatives
Scheme 2. Relevant Isomeric Structures of the Intermediate “C8H6O2” Speciesa
a Structure 5 has lost CO.
CID
- O-C H -CðOÞ-CH -X s X- þ “C H O ”
ð1Þ
f
6
4
2
8
6
2
The mass spectrometric experiments reported here do not
reveal any information about the nature of the neutral species
“C8H6O2”, which does not even need to be an intact entity. A
more definitive assignment by mass spectrometric means would
require more sophisticated methods,10,11 which cannot be ap-
plied in this particular case due to instrumental limitations. By
reference to the already existing mechanistic knowledge sum-
marized in Scheme 1, the “C8H6O2” species could thus corre-
spond to either the biradical 3, the cyclopropanone 4, the
quinomethane 5 as the product of decarbonylation, or as other
alternatives, such as the oxirane 7 or the ketene 8, which can be
formed via hydrogen migration following a Favorskii-type re-
arrangement. These structural alternatives are shown in
Scheme 2; note that the location of the radical centers in 3 is
only formal and the spin is likely to be located within the aromatic
ring system.12
When comparisons are made with condensed-phase experi-
ments, it is important to note that water is not involved in these
gas-phase studies. Though traces of water are present as a
background in the ion-trap mass spectrometer and react with
the primary product ions at extended time scales, the energizing
collisions in the CID experiments occur with the helium bath gas.
Therefore, the subsequent hydrolysis reactions of neutral
“C8H6O2” to phenylacetic acid 2 or of the quinomethane 5 to
6 do not play a role for the gas-phase fragmentations.
As an example, the ion abundances in the energy-resolved CID
spectra of mass selected -O-C6H4-C(O)-CH2-OP(O)(OEt)2
are summarized in Figure 1. At low collision energies, no
fragmentation takes place. Starting from an appearance energy
of about AE = 2.4 eV, the formation of -OP(O)(OEt)2
concomitant with loss of neutral C8H6O2 is observed and then
rapidly gains in intensity. Slightly above 3 eV collision energy, the
parent ion nearly disappears. With a branching ratio (BR) of 2%
for X = OP(O)(OEt)2, the loss of the corresponding acid (i.e.,
HOP(O)(OEt)2) with concomitant formation of an ion with
m/z 133 (i.e., deprotonated C8H6O2) is observed. Within experi-
mental error the fragmentation thresholds of these two channels
are identical, which might hint at the proposed mechanism
(see below). Of particular note is the relatively steep rise of the
Figure 1. Breakdown graph for the CID of the mass-selected phenolate
ion -O-C6H4-C(O)-CH2-OP(O)(OEt)2 ([) as a function of the
collision energy (in eV) to yield the fragments -OP(O)(OEt)2 (9,
-
m/z 153) and C8H5O2 (2, m/z 133). Both fragmentation channels
have the same appearance energy of AE = (2.4 ( 0.2) eV. In addition, the
graph shows the characteristic energy E1/2 at which 50% of the parent
ion fragments and the appearance energy AE derived from linear
extrapolation of the slope at E1/2 to the baseline.
fragmentation yield with increasing collision energy, indicating
that the fragmentation reaction involved in reaction 1 is not
subject to any pronounced entropic or kinetic restrictions that
are likely to arise from atom- or group-transfer reactions, more
complex structural rearrangements, or changes in spin state.
As detailed in the Introduction, the title compounds undergo a
very effective photolytic cleavage in the condensed phase. Given
the fact that the energies of about 2 eV required for fragmenta-
tion of the isolated ions in the gas phase are much lower than the
energy of the mid-UV photons (about 4 eV) typically used in
photodeprotection, two obvious questions arise: (1) Could the
reaction be initiated by a photoinduced deprotonation of the
phenol, followed by a nucleophilic attack starting from the
phenoxide ion to displace the leaving group and form 4 or 7?
(2) Can intersystem crossing of thermally excited phenoxide ions
serve as a plausible explanation for the facile fragmentation of
gaseous -O-C6H4-C(O)-CH2-X ions?
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Table 1. Summarized Appearance Energies (AE)a and Branching Ratios (BR) in the Dissociation of Mass-Selected -O-C6H4-
C(O)-CH2-X Ions Together with the Gas-Phase Acidities (ΔHacid in kJ mol-1) of the Conjugate Acids of the Leaving Groupsb
Xc
ΔHacid(HX)
AE(X-)
BR(X-)
AE(others)
BR(others)
othersf
TsO1b
MsO1b
1298
1343
1355
1.94
1.84
2.19
2.25
2.43
2.82
2.91
100
100
99
CF3COO
2.24
1
m/z 133
(PhO)2(O)PO1e,3c
(EtO)2(O)PO3e
p-CF3C6H4O
p-MeOC6H4COO
CH3COO3c,4c
HCOO
100
98
1387
1410
1426
1436
1449
1451
1463
1466
2.46
2.81
2.90
2.52
2.18
2.65
2.99
3.03
2
26
m/z 133
severald
74
90
10
m/z 133
- CH2CO
- CO
100
100
100
36
H2N(CH2)3COO2b
- C4H7NO
m/z 133
severale
C6H5O
3.04
3.30
64
4
p-MeOC6H4O
96
a The relative error of the AE values with regard to the quality of the fits is below (0.05 eV in all cases, whereas the absolute error is estimated as (0.2 eV.
b Values taken from the NIST Chemistry WebBook (http://webbook.nist.gov/chemistry/) in kJ mol-1. Values in italics are estimated from analogous
compounds which were in the database. c The references refer to the preparation of the various precursors; the synthesis of new derivatives is described in
the Supporting Information. d According to the mass differences observed, the majority of these side reactions are due to losses of HF (Δm = -20),
phenol (Δm = -94), and HX (Δm = -162). e According to the mass differences observed, these major fragmentation reactions are due to losses of CH3
•
•
(Δm = -15), CH3 þ phenol (Δm = -109), CH3OC6H4O• (Δm = -123), and “C9H8O3” (Δm = -164). f This column gives the major “other”
fragments (see the Supporting Information).
Scheme 3. Possible Neutral “C8H6O2” Products for Loss of
X- upon CID of -O-C6H4-C(O)-CH2-X and Their Notation
in the Theoretical Studies Including the Spin States (X =
CF3COO)a
Figure 2. Correlation of the experimentally determined appearance
energies (in eV) for the formation of X- upon CID of mass-selected -O-
C6H4-C(O)-CH2-X ions and the gas-phase acidities of the conjugate
acids (HX).
Similar to the example shown in Figure 1, we investigated
several other -O-C6H4-C(O)-CH2-X ions made by ESI of the
corresponding p-hydroxyphenacyl derivatives in the negative ion
mode. For all ions investigated, the CID breakdown behavior can
be reproduced reasonably well with simple sigmoid fits and the
a ISC stands for intersystem crossing between the spin states.
relevant branching ratios and appearance energies are summar-
ized in Table 1.
Interestingly, all fragmentation channels for an ion with a given
X start at the same appearance energies (within experimental
error), suggesting that the threshold values are subject to a
common, kinetically controlled step (e.g., the barrier of a Favorskii-
type process). In this context, we note that the appearance
energies were derived via linear extrapolations of sigmoid fits
of the fragment ion abundances to the energy axis. While this is
not the most elegant approach and, furthermore, we are assum-
ing energy-independent branching ratios where multiple frag-
mentations are observed, the data do provide a semiquantitative
comparison of the effect of the leaving group on the fragmenta-
tion process. This is illustrated by the reasonable correlation
between the appearance energies for the formation of X- and the
gas-phase acidities of the conjugate acids (HX) in Figure 2. It
should be noted, however, that some of the literature ΔHacid(HX)
values are associated with considerable error bars (e.g., (28
kJ mol-1 for MsOH) and that several others had to be estimated.
From this correlation we can roughly estimate that the
occurrence of reaction 1 for the simple carboxylates (i.e., X =
HCOO, CH3COO, and H2N(CH2)3COO) should have onsets
at about 3 eV. Obviously, the lower thresholds of their compe-
titive and specific fragmentations (i.e., loss of CO for formate,
loss of ketene for acetate, and loss of C4H7NO for γ-
aminobutyrate) suppress the formation of X- via reaction 1.13
To gain more insight into the reaction mechanism and the
possible neutral products (Scheme 3), we have investigated
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Figure 3. B3LYP/cc-pVTZ singlet potential energy surface for the fragmentation and rearrangements of [1-H]-. Energies are given in eV and refer to
0 K (the energies in parentheses are obtained at the B3LYP/6-31þG* level of theory). Only the most relevant channels are shown; for others see Table 2.
reaction 1 for X = CF3COO by means of density functional
theory, where all energies are given relative to the deprotonated
starting compound [1-H]- with X = CF3COO. For an initial
preoptimization, B3LYP calculations with the small 6-31þG*
were performed, while the discussion refers to the results
obtained with cc-pVTZ basis sets. The choice of X = CF3COO
for the computational study was due to the good quality of the
experimental data and negligible side reactions in conjunction
with the moderate size and the absence of heavier elements like
phosphorus or sulfur.
We have first explored possible fragmentations of [1-H]- in
the singlet ground state. Two possible scenarios are proposed.
The elimination of CF3COO- can be assisted by the closing of
Figure 4. Estimated surface crossing (energies in eV) between the
either an oxirane ring or a cyclopropanone ring. The first reaction
opening spirodione (blue, singlet) and the closing diradical (red, triplet)
pathway is associated with an energy barrier of 0.99 eV (TS
derived from B3LYP/6-31þG* geometry optimizations with a fixed
11/19) and leads to a van der Waals complex 19. The breakup of
the complex 19 yields the oxirane product 17 concomitant with
free CF3COO-. The concurrent fragmentation of [11-H]- leads
via a larger energy barrier of 1.39 eV (TS 11/110) to a van der
Waals complex 110, which after elimination of CF3COO-, yields
length of the (opening/closing) C-C bond.
of AE = (2.2 ( 0.2) eV for X = CF3COO (Table 1), the apparent
CID threshold from experiment cannot be used as a criterion to
distinguish these channels. A reasonable agreement between the
computed and experimentally found endothermicities associated
with the formation of CF3COO- also lends further support to
the calibration of the energy scale used in the CID experiments.15
The major difference among the possible products concerns
their spin multiplicities. Given that the reactant ion 1[1-H]- is a
1
the spirodione 4. The spirodione can further undergo a facile
decarbonylation via the transition state TS 14/15, which is only
1
0.37 eV higher in energy, and provide the enone product 5.
1
1
Interestingly, both primary “C6H8O2” products 4 and 7 are
almost isoenergetic and the barriers en route to these neutral
fragments are lower than the exit channels themselves, i.e. there
are no barriers in excess of the overall reaction endothermicities.
Accordingly, the fragmentation is likely to be under thermo-
3
singlet, formation of 3 would require a spin flip along the
reaction coordinate (“two-state reactivity”),16 whereas formation
of 14 and 17 can proceed on a single spin surface as depicted in
Figure 4. Though it is often implied that effective spin changes
require the presence of heavy elements and/or transition metals,
some rather simple CHO compounds have been shown to obey
two-state scenarios in their dissociation (e.g., CH3Oþ, C2O2, and
C2O42þ).17,18 Hence, the spin argument cannot be used to a
1
1
chemical control and hence 4 and 7 both should be formed
during the dissociation of [1-H]-.
We explored the possible involvement of the biradical frag-
ment 33. The formation of the biradical (1[1-H]- f 33 þ X-)14
requires only slightly more energy (2.10 eV, Table 2) than those
1
1
of the singlet products 4 and 7 (Figure 3). Given that the
3
priori exclude the high-spin product 3.19 If we consider the
3
1
calculated energy demands for the formations of 3, 4, as
well as 17 are all within the range of the experimental estimate
singlet and triplet potential energy curves calculated along the
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Table 2. Calculated Energetics (relative energies at 0 K in eV)
of -O-C6H4-C(O)-CH2-OOCCF3 and Its Possible Fragments
at the B3LYP/cc-pVTZ Level of Theory
groups, again, no formation of X- was observed and loss of
ketene prevailed instead with thresholds of 2.90 eV for the
2-cyano and 2.96 eV for the 3-cyano compared to only 2.52 eV
for the all-H compound. The emerging trends for substitutions of
the phenacyl core can by and large be attributed to mere
thermodynamic effects operating on the respective reactant
anions [1-H]-. Thus, donors such as methoxy substituents are
expected to decrease the electron affinity of the neutral counter-
part [1-H]• and thus also decrease the stability of the [1-H]-
anion. However, in the products resulting from dissociation of
[1-H]- according to reaction 1, the substituents in the phenacyl
core end up in the neutral product and mere electron-with-
drawing or -donating effects thus become much less important.
Hence, for a given X, the dissociation threshold is likely to be
determined more by the thermochemical properties of the
precursor ion [1-H]-. Consistent with this line of reasoning
are the significantly elevated AE values of the cyano-substituted
derivatives, where the electron-withdrawing substituents primar-
ily stabilize the precursor [1-H]-, whereas the corresponding
effect on the neutral product of reaction 1 is much smaller. In fact,
these findings parallel the photochemistry in the condensed
phase. In a comparative investigation of a broad range of
substituent effects that included F, MeO, CN, CO2R, CONH2,
and CH3 on the photochemical rearrangements of p-hydroxy-
phenacyl esters, there was little effect on either the rate or the
quantum efficiency for the photo-Favorskii rearrangement and
the release of the acid leaving group or on the lifetimes of the
reactive triplet state.20
Erel
1[1-H]-
0.00a
2.10
1.99
2.80
2.36
3.01
3.48
0.85
2.59
2.02
1.39
0.30
33 þ CF3COO-
14 þ CF3COO-
TS 33/35 þ CF3COO-
TS 14/15 þ CF3COO-
TS 14/17 þ CF3COO-
TS 14/18 þ CF3COO-
15 þ CO þ CF3COO-
35 þ CO þ CF3COO-
17 þ CF3COO-
18 þ CF3COO-
180 þ CF3COO-
a Total energy: -985.384563 hartree.
elongated C-C bond of the spirodione and the shortened C-C
bond of the biradical (Figure 4), we find that the crossing of both
curves is located about 0.5 eV above the respective minima.
Another aspect, perhaps unusual for synthetic chemists, is that
structure 3 does exist only as a triplet and structure 4 only as a
1
3
singlet, in that neither 3 nor 4 are minima on the respective
potential energy surface. Intersystem crossing of 33 to the singlet
surface is thus associated with a ring closure to afford 14 and the
reverse process corresponds to ring-opening (Scheme 3).
The high strain energy of the cyclopropanone 14 prompted us
to probe its rearrangement via hydrogen migration. Though the
resulting ketene 18 is significantly more stable than 33 as well as
14 (Table 2), the energy barrier resulting from the associated
transition structure TS 14/18 (Erel = 3.48 eV) excludes this as a
relevant intermediate in the experiment. Likewise, a tautomer of
’ CONCLUSIONS
Collision-induced dissociation of mass-selected p-hydroxy-
phenacyl derivatives as their conjugate bases, i.e. -O-C6H4-
C(O)-CH2X, with various leaving groups X was probed by
means of ion-trap mass spectrometry. The losses of X- con-
comitant with formal generation of “C8H6O2” have surprisingly
small thresholds and occur with high efficiencies once the
reaction endothermicity is provided in the collision experiments
for most leaving groups X. Simple carboxylates such as X =
HCOO or CH3COO, however, follow different fragmentation
pathways. Detailed computational studies using density func-
tional theory for X = CF3COO reveal a competition of two
pathways and two spin surfaces for the loss of trifluoroacetate
from the conjugate base of p-hydroxyphenacyl. In fact, we face a
situation in which C-X bond heterolysis leads to cyclopropa-
none 14 or oxirane 17 on the singlet surface and to the biradical 33
for triplet spin. The energy demands of about 2 eV for all three
pathways are too close to each other to allow an assignment of
the preferred route with regard to the errors in both theory and
experiment. Nevertheless, crossing between 33 and 14 is expected
to be facile at ambient temperatures, and structure 4 may be
regarded as a direct precursor for the formation of p-hydroxy-
phenylacetic acid and quinomethane 5 that hydrolyzes to 6.
Last, but not least, let us phenomenologically try to extrapolate
the gas-phase data to the condensed phase. At first, it is obvious
that the phenoxide group will experience a significant stabiliza-
tion upon solvation, such that the activation energy associated
with C-X bond heterolysis is expected to be larger in solution.
Next, several rearrangements which are relatively difficult in the
gas phase, in particular the tautomerizations 4 f 8 and 8 f 80,
will proceed much more efficiently in protic solvents. In fact, an
intimate interaction of water molecules with intermediates such
1
18, (4-hydroxyphenyl) ketene 80, is rather stable, but not
accessible in a direct rearrangement from either 33 or 14.
3
Furthermore, decarbonylation of the diradical 3 and the spiro
compound 14 that affords quinomethane 5 in either spin state is
quite favorable if the singlet products are formed, but the barriers
involved (TS 33/35, Erel = 2.80 eV and TS 14/15, Erel = 2.36 eV)
appear too large to account for the experimental findings.
Correlating the experimental data (apparent thresholds and
energy behavior) as well as the theoretical findings (minima,
barriers, and spin states), we conclude that close to the threshold
reaction 1 for X = CF3COO can lead to the cyclopropanone 14 or
the oxirane 17 with nearly equal probability. At elevated energies
the triplet biradical 33 may also contribute. We note in passing
that B3LYP/cc-pVTZ predicts the gas-phase acidity of
CF3COOH in the correct range (1371 kJ mol-1 compared to
the experimental value of 1355 ( 12 kJ mol-1).
In addition, some phenacyl compounds with differently sub-
stituted aromatic moieties were probed in order to elucidate
possible electronic effects. The influence of methoxy substitution
was examined for X = (EtO)2(O)PO, where AE(X-) = 2.43 eV
was obtained for the unsubstituted parent p-hydroxyphenacyl
compound (Table 1), whereas the 2-methoxy- and 3,5-
dimethoxy phenacyl ions gave AE values of 2.42 and 2.34 eV,
respectively. These differences are, however, within the experi-
mental error margins of about (0.05 eV in the relative and (0.2
eV in the absolute CID thresholds. For cyano-substituted
phenacyl derivatives with X = CH3COO as potential leaving
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as 4 may very much facilitate the interconversion to derivatives of
phenylacetic acid. In future studies, we will try to address the
latter aspect by investigation of the gas-phase chemistry of
partially solvated ions derived from p-hydroxyphenacyl precur-
sors using not only CID, but also experiments at elongated
reaction times in the presence of water and possibly also spectro-
scopic methods.9
this level of theory, all stationary points discussed had only positive
frequencies and thus correspond to genuine minima. Harmonic fre-
quency analysis was also used to obtain thermochemical data. All
calculations refer to the gaseous state in that additional solvation,
aggregation, etc. is deliberately not included in order to match the
present experimental conditions.
’ ASSOCIATED CONTENT
’ EXPERIMENTAL AND COMPUTATIONAL DETAILS
S
Supporting Information. Synthesis of new pHP esters
b
and their spectroscopic properties, breakdown graphs of all ions,
additional data about ion fragmentations, and the Cartesian
coordinates of the computed structures. This material is available
free of charge via the Internet at http://pubs.acs.org.
The measurements were performed with an ion-trap mass spectro-
meter (IT-MS) that has been described elsewhere21 by electrospray
ionization of dilute methanolic solutions of the p-hydroxyphenacyl
derivatives HO-C6H4-C(O)-CH2-X. In brief, our IT-MS bears a con-
ventional ESI source consisting of the spray unit (typical flow rate 5 μL/
min, typical spray voltage 5 kV) with nitrogen as a sheath gas, followed
by a heated transfer capillary (kept at 200 °C), a first set of lenses which
determine the soft- or hardness of ionization by variation of the degree of
collisional activation in the medium-pressure regime,22-24 two transfer
octopoles, and a Paul ion-trap with ca. 10-3 mbar helium for ion storage,
manipulation, and a variety of MSn experiments.21,25 In the ESI source,
the sample solution is evaporated at room temperature in the presence of
a nitrogen stream and assistance by a kV voltage. The spray then passes
through a high-temperature zone (typically operated at 200 °C) that
facilitates droplet shrinkage and propels the spray into the differential
pumping system. The nascent ions are then transferred to the mass
spectrometer. For detection, the ions are ejected from the trap to an
electron multiplier. Note that in the standard mode of operation, the IT-
MS used has a low-mass cutoff at m/z 50.13 In the present experiments,
the instrument was operated in negative ion mode, the corresponding
deprotonated ions -O-C6H4-C(O)-CH2-X (X = leaving group) were
mass-selected, and then subjected to collision-induced dissociation
(CID) by application of an excitation AC voltage to the end-caps of
the trap to induce collisions of the isolated ions with the helium buffer
gas. In a CID experiment, the ion of interest is gradually excited
kinetically and allowed to collide with helium as a nonreactive collision
partner, which causes ion fragmentations. Note that rearrangements
themselves are “invisible” in standard MS because these are not
associated with mass changes. When the CID experiments are con-
ducted at variable collision energies, quantitative reaction thresholds can
be derived.26 In the present IT-MS experiments, we used an ion-
excitation period of 20 ms, for which we have recently introduced a
phenomenological linear conversion factor for the extraction of approx-
imate appearance energies (AE) based on comparisons with reference
molecules of known bond sþtrengths,15 i.e., Ag(CH3OH)þ, Ag-
(CH3OH)2þ, and Fe(C5H5)2 as suggested by O’Hair and co-
’ AUTHOR INFORMATION
Corresponding Author
roithova@natur.cuni.cz; detlef.schroeder@uochb.cas.cz
’ ACKNOWLEDGMENT
This paper is dedicated to Professor Siegfried Blechert on the
occasion of his 65th birthday. This work was supported by the
Czech Academy of Sciences (Z40550506), the European Re-
search Council (AdG HORIZOMS), the Ministry of Education
of the Czech Republic (MSM0021620857), and the National
Institutes of Health (RO1GM72910).
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.
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The Journal of Organic Chemistry
ARTICLE
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