Tosyl oxygen transfer and ion-neutral complex mediated electron transfer in the gas-phase fragmentation of the protonated N-phenyl p-toluenesulfonamides

Article abstract of DOI:10.1016/j.ijms.2014.11.003

In this work, an interesting oxygen transfer reaction in the gas phase dissociation of N-phenyl p-toluenesulfonamides has been explored by combination of the ESI-MS techniques and theoretical calculations. The protonated molecules underwent dissociation reactions, upon collisional activation, to give the [tosyl cation/aniline] ion-neutral complex (INC), in which the coupling reactions subsequently occurred to afford an ionic species of toluenesulfinate. The subsequent reactions of the toluenesulfinate species resulted in generation of the protonated 6-iminocyclohexa- 2,4-dienone or the 2-aminophenol radical cation, via cleavage of the SO bond. The above processes involved the tosyl oxygen transfer, and calculation results indicated that both the ortho- and the para- positions at the aniline ring are favorite for the tosyl oxygen transfer, and formation of radical cation involved an INC mediated electron transfer. The isomeric N-methylphenyl p-toluenesulfonamides behaved significant difference in the CID-MS spectra, indicating that the three isomers can be distinguished by ESI-MS.

Full text of DOI:10.1016/j.ijms.2014.11.003

International Journal of Mass Spectrometry 376 (2015) 6–12
Contents lists available at ScienceDirect
International Journal of Mass Spectrometry
journal homepage: www.elsevier.com/locate/ijms
Tosyl oxygen transfer and ion–neutral complex mediated electron
transfer in the gas-phase fragmentation of the protonated N-phenyl
p-toluenesulfonamides
Shanshan Wanga, Cheng Guob, Ningwen Zhanga, Yanqing Wua, Huarong Zhanga,∗
,
Kezhi Jianga,∗
a Key Laboratory of Organosilicon Chemistry and Material Technology, Hangzhou Normal University, Hangzhou 311121, China
b Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 July 2014
Received in revised form 30 October 2014
Accepted 2 November 2014
Available online 8 November 2014
In this work, an interesting oxygen transfer reaction in the gas phase dissociation of N-phenyl p-
toluenesulfonamides has been explored by combination of the ESI–MS techniques and theoretical
calculations. The protonated molecules underwent dissociation reactions, upon collisional activation, to
give the [tosyl cation/aniline] ion–neutral complex (INC), in which the coupling reactions subsequently
occurred to afford an ionic species of toluenesulfinate. The subsequent reactions of the toluenesulfinate
species resulted in generation of the protonated 6-iminocyclohexa- 2,4-dienone or the 2-aminophenol
radical cation, via cleavage of the S O bond. The above processes involved the tosyl oxygen transfer, and
calculation results indicated that both the ortho- and the para- positions at the aniline ring are favorite for
the tosyl oxygen transfer, and formation of radical cation involved an INC mediated electron transfer. The
isomeric N-methylphenyl p-toluenesulfonamides behaved significant difference in the CID–MS spectra,
indicating that the three isomers can be distinguished by ESI–MS.
Keywords:
Oxygen transfer reactions
N-phenyl p-toluenesulfonamides
Ion–neutral complex
Electron excitation
CID–MS
DFT
© 2014 Elsevier B.V. All rights reserved.
1. Introduction
phenylsulfonyl oxygen [13–15]. Dissociation of protonated N-alkyl-
p-toluenesulfonamides has been reported to occur effectively via
Aromatic sulfonamides and their derivatives, which contain
an oxidized sulfur group, play a significant role in develop-
ing therapeutics for diabetes and Alzheimer’s disease as well
as bacterial infections [1–6], and have been widely deployed
as drug candidates in the pharmaceutical industry. To facili-
tate identification of sulfonamides and the relevant unknown
compounds, sulfonamides have been extensively investigated
experimentally and theoretically in explanation on their mecha-
nistic fragmentation pathways occurring in electrospray ionization
mass spectrometry [7–17]. Elimination of SO2 has been reported
to effectively occur in the tandem MS of the protonated and the
deprotonated sulfonamides, which can be viewed as a structure
specific mass spectrometric strategy for detection of sulfona-
mides [7–12]. The characteristic loss of SO has been observed
in dissociation of p-amino-phenylsulfonyl cation via an intra-
molecular SNAr reaction, accompanied with the transfer of the
cleavage of either the S N bond or the N C bond to form two
different ion–neutral complexes, which leads to the p-tosyl cation
and the protonated p-toluenesulfonamide (or carbocation), respec-
tively [16]. Fragmentation of protonated benzenesulfonamides,
on the other hand, mainly affords an ion–neutral complex (INC)
[phenylsulfonyl cation/aniline], which undergoes the subsequent
charge transfer between the two partners of the complex and gives
rise to the radical cation of anilines [17]. Transfer of the tosyl
oxygen has also been found in fragmentation of protonated sulfo-
namides [17], but no detailed mechanism has been documented to
our knowledge. In this work, the N-phenyl p-toluenesulfonamides
were selected as a model to perform a detailed mechanistic investi-
gation on the transfer of tosyl oxygen, which leads to two fragment
ions of the oxidized anilines.
2. Experimental
2.1. Materials
∗
Corresponding authors. Tel.: +86 13605705802.
E-mail addresses: zhanghuaxy99@gmail.com (H. Zhang),
Toluenesulfonaniline derivatives (compounds 1–10 in
jiangkezhi@hznu.edu.cn (K. Jiang).
Scheme 1) were synthesized according to the classical method,
http://dx.doi.org/10.1016/j.ijms.2014.11.003
1387-3806/© 2014 Elsevier B.V. All rights reserved.

S. Wang et al. / International Journal of Mass Spectrometry 376 (2015) 6–12
7
O
H
1, R = H;
2, R = p-OCH3;
3, R = p-Cl;
4, R = o-CH3;
5, R = m-CH3;
6, R = p-CH3;
S N
O
R
O
O
H
H
S N
O
S N
O
7
8
O
H
O
H
S N
O
S N
O
9
10
Scheme 1. The structures of sulfonamides.
involving reaction of p-toluenesulfonyl chloride (or benzenesul-
fonyl chloride) with the corresponding amine in the presence of
pyridine [18]. All compounds were purified after synthesis, and
their structures were further confirmed by MS.
Fig. 1. The CID–MS spectrum of (a) [1 + H]+, (b) [1 + D]+ and (c) [1 − H + 2D]+.
3. Results and discussion
2.2. Mass spectrometry
3.1. Dissociation of the protonated N-phenyl
p-toluenesulfonamides
The ESI–MS/MS experiments were performed on an LCQ
quadrupole ion trap mass spectrometer (Thermo-Finnigan LCQ
Advantage MAX, ThermoFisher Scientific Inc., USA) [19], equipped
with an ESI ion source in the positive ionization mode, with data
acquisition using the Xcalibur software (Version1.4). Diluted solu-
tions (about 10 ppm) were prepared by dissolving the sulfonamide
sample in a mixed solvent of methanol and water (V:V = 1:1), and
then were introduced into the source chamber at a flow rate of
5 ␮L min−1. The sheath gas (N2, 99.99%) was set at 25 arbitrary
units (a.u.), the spray voltage at −4.5 kV, and the heated ion
transfer tube (250 ◦C) at +55 V, respectively. The ion trap pressure
of approximately 2 × 10−5 Torr was maintained with a Turbo pump
and pure helium (99.999%) was used for the trapping and collision
activation of the selected ions. The CID–MS experiments were per-
formed by application of an excitation AC voltage to the end caps of
the ion trap to induce collisions of the isolated ions (isolation width
at 1.2 u.) for a period of 30 ms and variable excitation amplitudes.
Note that the software of Finnigan ion trap applies a ‘normal-
ized collision energy’ (see Finnigan Product Support Bulletin 104:
Investigation of the tosyl oxygen transfer reaction has been
carried out by exploring the fragmentation behaviors of the pro-
tonated sulfonamides (Table 1). N-phenyl p-toluenesulfonamide
(1) was selected as a model to perform a detail investigation. Fig. 1a
describes the CID–MS spectrum of [1 + H]+, in which the product ion
at m/z 155 is ascribed to the tosyl cation (a-1IP), resulted from the
direct separation of the [tosyl cation/aniline] INC, originating from
dissociation of [1 + H]+ (m/z 248). Also, charge transfer in the INC
results in the aniline radical cation (a-2IP) at m/z 93 [17]. The frag-
ment ions at m/z 108 and m/z 109 is attributed to the protonated
quino-imines (e.g. 1c-1IP) and the hydroxyaniline radical cation
(e.g. 1c-2IP), respectively. The product ion at m/z 174 is ascribed
to be the protonated phenylsulfamic acid, resulting from toluene
elimination and hydration of the precursor ion [25–29]. The ele-
mental compositions of these fragment ions have been determined
by analyzing their accurate masses measured with high resolu-
tion Q-TOF mass spectrometer (Supplementary Table S1 and Fig.
S1). Thus, the potential fragmentation pathways were proposed in
http://www.thermo.com/eThermo/CMA/PDFs/Articles/articlesFile 21418.pdf)
Scheme 2. Noteworthy, formation of the fragment ions at m/z 108
by which mass of the target ion is automatically considered in the
calculation of the excitation amplitude in the CID experiments
[20–23]. Each mass spectrum was the average of over 50 scans.
and m/z 109 can only be interpreted as a result of the transferring
the tosyl oxygen to the aniline ring, which involves an interesting
intramolecular oxidation-reduction reaction.
The proposed fragmentation pathways in Scheme 2 have been
supported by the deuterium labeling experiments (Fig. 1). The
deuterated molecule ([1 + D]+, m/z 249) and the di-deuterated
one ([1 − H + 2D]+, m/z 250) were generated by spraying a diluted
methanol-d4 solution of 1 prepared freshly and that placed for sev-
eral minutes, respectively. There is no external proton or sulfamidic
hydrogen in the fragment ion of a-1IP, and thereby decompo-
sition of the [1 + H]+, [1 + D]+ and [1 − H + 2D]+ species resulted
in the tosyl cation with the same mass (155 Da) via the loss of
C6H5NH2, C6H5NHD and C6H5ND2, respectively. The fragment ion
a-2IP contains both external proton and sulfamidic hydrogen from
the precursor ion. As expected, the corresponding mass (93 Da) of
a-2IP shifts to 94 Da originating from [1 + D]+, and to 95 Da from
[1 − H + 2D]+, respectively. Similarly, the corresponding m/z of the
ions at m/z 108 (e.g. 1c-1IP) and m/z 109 (e.g. 1c-2IP) shift to m/z
109 and m/z 110 in the CID–MS of [1 + D]+ (Fig. 1-b), and to m/z 110
and m/z 111 in the CID–MS of [1 − H + 2D]+ (Fig. 1-c), respectively.
Interestingly, no H/D exchange occurs for these fragment ions in
the CID process.
2.3. Theoretical calculations
The theoretical calculations were performed using the Gaussian
09 program [24]. The equilibrium geometries of the target species
were optimized using the density functional theory (DFT) method
at the B3LYP/6-311 + G(d,p) level. The optimized structures were
identified as the true minima in energy by the absence of imaginary
frequencies. Transition states, on the other hand, were identified
by the presence of one single imaginary vibration frequency and
the normal vibrational mode, and further confirmed by the intrin-
sic reaction coordinates (IRC) calculations. The electron excitation
energy of a target species was obtained by the Configuration Inter-
action approach (CI-Singles). The energies discussed here are the
sum of the associated electronic and thermal free Energies. The DFT
optimized structures were shown by Gauss View (Version 3.09)
software to give higher quality images of these structures. The
energies discussed here are the sum of electronic and thermal free
energy.

8
S. Wang et al. / International Journal of Mass Spectrometry 376 (2015) 6–12
Table 1
The CID–MS data of the protonated p-toluenesulfonamides in Scheme 1 at the normalized collision energy (NCE) of 18%.
Compound
R
[M + H]+ m/z (%)
Product ions, m/z (%)
Aniline radical cation
RC6H4NH2
Phenylsulfonyl
cation RC6H4SO2
Protoanted 6-imino
cyclohexa2,4-
dienone
Aminophenol
radical cation 1e-IP
Others
+.
+
1d-IP
1
2
3
4
5
6
H
248(17.9)
278(100.0)
282(16.6)
262(17.5)
262(30.0)
262(7.4)
93(100.0)
123(20.5)
127(100.0)
107(100.0)
107(100.0)
107(100.0)
93(100.0)
–
155(18.6)
155(0.2)
155(19. 7)
155(0.1)
155(0.1)
–
108 (10.3)
138(1.4)
–
122(4.8)
122(32.8)
122(0.4)
108 (8.7)
–
109(43.0)
–
92(0.2)
122(0.5)
126(0.2)
106(4.0)
106(1.3)
106(15.0)
92(0.04)
172(100.0)
*
p-CH3O
p-Cl
o-CH3
m-CH3
p-CH3
H
143(1.0)
123(11.5)
123(20.7)
123(1.1)
109(11.8)
–
7
234(6.7)
228(20.6)
–
–
8**
–
*
“–” Means “not detected”.
The backbone structure of 8 is significantly different to compounds 1–6.
**
Migration of the tosyl oxygen has consolidated by comparing the
There are three potential sites (ortho, meta and para) at the
aniline ring for the tosyl oxygen transfer. N-3,4,5-trimethylphenyl
p-toluenesulfonamide (9, blocking the meta and the para positions),
and N-2,6-dimethylphenyl p-toluenesulfonamide (10, blocking the
ortho positions) were synthesized for the CID–MS experiments
(Fig. 2). For compound 9, both the radical ion of hydroxyaniline
(m/z 151) and the protonated quino-imines (m/z 150) have been
obtained in the ESI–MS/MS spectra, which consolidated that migra-
tion of the tosyl oxygen occurs to the ortho position in the CID
process. For the occurrence of compound 10, both the radical ion
of hydroxyaniline (m/z 137) and the protonated quino-imines (m/z
136) have also been obtained in the CID–MS experiment, indicat-
ing that the tosyl oxygen can also be transferred to the meta or the
para position of the aniline ring. Thereby, the tosyl oxygen atom can
be transferred to the ortho, meta, and para positions of the aniline
ring in the CID process. Further investigation was performed in the
succeeding sections.
fragmentation behavior of the derivatives of sulfonamide (Table 1).
For compounds 2–6 with different substituents on the aniline ring,
the fragment ions (e.g. 1c-1IP, 1c-2IP) formed via tosyl oxygen
transfer showed a mass shift corresponding to the mass of the sub-
stituent. For example, compound 5 possesses a methyl group at the
aniline ring, and thus there was an increasing mass shift of 14 Da
for the relevant ionic fragments 1c-1IP (or 2c-1IP, 3c-1IP) (from
m/z 108 to m/z 122) and 1c-2IP (or 2c-2IP, 3c-2IP) from m/z 109
to m/z 123). As for compound 7 with different substituent at the
sulfonyl moiety, however, no mass shift was found for the relevant
ionic fragments. Thereby, the ionic products 2d-IP and 2e-2IP come
from the aniline moiety, which bonds with the transferring tosyl
oxygen atom in the coupling way. However, no relevant product
was obtained in dissociation of [8 + H]+, indicating that migration
of the tosyl oxygen in Scheme 2 is inhibited in fragmentation of
protonated N-alkyl-p-toluenesulfonamides [16].
O
S
O
O
3
2
12
5
O
S
S
1
4
6
NH2
NH2
7
O
a-1IP m/z 155
O
11
8
a
m/z 248
9
10
H2N
inc1 m/z 248
a-2IP m/z 93
NH2
OH
S
OH
OH
S
O
S
O
NH2
O
3c m/z 248
2c m/z 248
NH2
1c m/z 248
NH2
O
NH2
NH2
O
S
S
NH2
O
S
NH2
O
3c-1IP
m/z 108
OH
NH2
O
O
OH
2c-1IP
OH
inc4 m/z 248
1c-1IP
m/z 108
inc6 m/z 248
m/z 108
inc3 m/z 248
NH2
NH2
OH
H2N
OH
2c-2IP m/z 109
OH
3c-2IP m/z 109
1c-2IP m/z 109
Scheme 2. The proposed oxygen transfer reactions in the fragmentation of [1 + H]+.

S. Wang et al. / International Journal of Mass Spectrometry 376 (2015) 6–12
9
of the single imaginary frequency (i211.75 cm−1) corresponds to
˚
extension of the N6 S5 bond (3.380 A) accompanied with oscilla-
tion of the two amide protons to form two intramolecular hydrogen
˚
˚
bonds (2.404 A and 2.696 A) with the two tosyl oxygen atoms.
INC is an interesting and important intermediate in the gas
phase chemistry, and various chemical reactions may occur either
in the ionic fragment alone or between the two partners prior to its
final separation [16,17,34]. Interestingly, the calculated electronic
excitation energy is negative (−0.6215 eV) for inc1, indicating that
inc1 can spontaneously undergo electron excitation along with
electron transfer to generate the triple inc1-t, consisting of a p-
tolylsulfinyl radical and an aniline radical cation. The triple inc1-t
lies 65.2 kJ mol−1 below the singlet one in free energy. The more
stability of inc1-t is attributed to the two stronger intramolecular
´
´
´
˚
˚
˚
hydrogen bonds (2.216 A and 2.216 A in inc1 versus 2.134 A and
´
˚
2.053 A in inc1-t) and the more p–␲ conjugation of the N6 C7 bond
´
˚
´
˚
Fig. 2. The CID–MS spectra of (a) [9 + H]+, and (b) [10 + H]+.
(1.348 A in inc1 versus 1.328 A in inc1-t). Decomposition of inc1
and inc1-t affords the tosyl cation (a-1IP, m/z 155) and the aniline
radical cation (a-2IP, m/z 93), respectively.
3.2. The mechanistic pathway of the oxygen transfer
Alternatively, the two partners in inc1 can undergo the cou-
pling reactions between the sulfonic group and the aniline ring,
and afford protonated toluenesulfinates (e.g. 1c), accompanied with
migration of the activated hydrogen (the ipso-H on the analinic
ring) to the sulfinyl O12. Due to the different coupling site (ortho,
meta, and para) at the aniline ring, there are three potential iso-
meric species of protonated toluenesulfinates (1c, 2c and 3c) via
the transition state of inc1-TS1, inc1-TS2 and inc1-TS3. As shown in
Fig. 4, all these transition states show a shortening O11–C distance
To gain more detailed insights into the competing oxygen migra-
tion reactions (Scheme 2), DFT calculations have been preformed
at the B3LYP/6-311 + G(d,p) level of theory for fragmentation of the
typical [1 + H]+. Fig. 3 displays a potential energy diagram for the
dissociation reactions as presented in Scheme 2, and the details
structures of the corresponding species are available as Fig. 4 and
Supplementary Fig. 2S.
To begin the mechanistic investigation on the oxygen transfer
in fragmentation of [1 + H]+, we should first identify the original
protonation site of the molecule. There are two potential protona-
tion sites for compound 1: (i) protonation at the sulfonamic N6 to
generate the ionic species a and (ii) at the tosyl O11 (or O12) to
afford b. The calculated free energy of a is 36.5 kJ mol−1 lower than
that of b, indicating a much more preferred protonation site of the
sulfonamide N atom [17]. The sulfonamide N is also reported by the
NMR investigation to be preferably protonated in solutions [30–33].
Noteworthy, inter-conversion between a and b is difficult to occur
via 1,3-proton transfer, due to a considerable energy barrier (a-TSb)
˚
˚
˚
(2.248 A in inc1-TS1, 1.706 A in inc1-TS2 and 2.699 A in inc1-TS3) in
structure. It should be noteworthy that this process involves migra-
tion of the tosyl O11 atom and reduction of the tosyl S5 atom. Also, a
can directly undergo an intramolecular tosyl oxygen transfer reac-
˚
tion (a-TS2) to afford 1c, via breakage of the N6 S5 bond (2.837 A)
˚
and coupling of the tosyl oxygen with the phenyl ring (1.931 A for
the O11–C8 distance).
The subsequent dissociation of 1c (2c or 3c) via the breakage of
the S5 O11 bond leads to completion of the tosyl oxygen transfer
to the aniline ring, and affords the product ions of the proton-
ated quino-imines (e.g. 1c-1IP, m/z 108) and the hydroxyaniline
radical cations (e.g. 1c-2IP, m/z 109) in two competing reaction
channels, respectively. Here, 1c was selected as an example to illus-
trate the two competing dissociation channels. The subsequent
charge-directed decomposition of 1c leads to an INC of inc2 via
the transition state 1c-TS1. Direct separation of inc2 affords the
protonated 6-iminocyclohexa-2,4-dienone (1c-1IP, m/z 108).
The mobile H8 in inc2 can also be effectively transferred to
of 133.7 kJ mol−1
Protonation at the sulfonamide N6 in a weakens the N6 S5
.
˚
bond, as indicated by the lengthened bond length (1.635 A in
˚
b versus 2.073 A in a). Cleavage of the N6 S5 bond in a, upon
collisional activation, leads to formation of inc1, an ion–neutral
complex (INC) consisting of a tosyl cation and a neutral aniline,
which surmounts an energy barrier of 98.4 kJ mol−1 via the transi-
tion state of a-TS1. As for the optimized structure of a-TS1 (Fig. 3),
which has not been obtained previously [17], the vibrational mode
phenolic oxygen O11 with a small energy barrier of 14.7 kJ mol−1
,
which results in formation of another ion–neutral complex (inc3).
Analogous to inc1, the triple state (inc3-t) of inc3 is thermo-
dynamically more stable than the corresponding singlet one by
63.5 kJ mol−1. As shown in Fig. 4, there are two intramolecular
hydrogen bonds in both inc3 and inc3-t, with the types of N H. . .O
and O H. . .O. The calculated electronic excitation energy is also
negative one (−2.3467 eV), and thus inc3 is spontaneously con-
verted to the triple state one along with electron transfer between
the two partners of the INC. Decomposition of inc3-t results in the
2-aminophenol radical cation (1c-2IP, m/z 109).
As shown in Fig. 3, the energy barrier of the four tosyl trans-
fer processes follows the order of 2c-TS1 (128.9 kJ mol−1) ∼ a-TS2
(128.1 kJ mol−1) > 1c-TS3 (77.8 kJ mol−1) ∼ 3c-TS1 (75.8 kJ mol−1).
Thereby, a prefers to undergo the INC mediated tosyl oxygen
migration in the CID process, rather than a direct transfer (via
a-TS2). The order of prior site for most for the tosyl oxygen trans-
fer is ortho ∼ para > meta site in the anilinic ring. Analysis of the
potential energy diagram in Fig. 3 indicated that the INC-mediated
Fig. 3. The potential energy diagram for the oxygen transfer in dissociation of
[1 + H]+.

10
S. Wang et al. / International Journal of Mass Spectrometry 376 (2015) 6–12
Fig. 4. The optimized structures of the key species involved tosyl oxygen transfer and ion–neutral complex mediated electron transfer in dissociation of [1 + H]+ at the
b3lyp/6-311 + g(d,p) level.
O
C coupling reaction is the common key step in the compet-
ion at m/z 122 from the three isomers follows the reverse order
of meta- (32.8%) > ortho- (4.8%) > para- (0.4%), due to the block of a
methyl group at differentsite of the aniline ring. Similar results have
obtained for the fragment ions at m/z 123: meta- (20.7%) > ortho-
(11.5%) > para- (1.1%). Additionally, the ion at m/z 123 is more abun-
dant than the ion at m/z 122 for the ortho- and the para-isomers,
while the meta- isomer shows the opposite result.
ing reaction channels of tosyl oxygen migration. Formation of the
hydroxyaniline radical cation at m/z 109 (1c-2IP, 2c-2IP or 3c-2IP)
is thermo-dynamically more favored than that of the protonated
quino-imines at m/z 108 (1c-1IP, 2c-1IP or 3c-1IP), which is in good
agreement with the experimental results (Table 1).
3.3. Differentiation of the isomeric N-methylphenyl
p-toluenesulfonamides
Three methyl-substituted isomers (compounds 4–6) were
selected to investigate the positional factor on the fragmentation
behaviors (Fig. 5). Different to compound 1, the tosyl cation (m/z
155) was not observed in the CID–MS of the three isomers. Inter-
estingly, an extra fragment ion at m/z 106 (4-PH, 5-PH or 6-PH),
resulting from hydride transfer in the [tosyl cation/methylaniline]
INC [34] (Scheme 1S), was observed in the CID–MS. Due to the dif-
ference in the substituent mode, the stability of the fragment ions
at m/z 106 follows the order of 6-PH (para, 15.0%) > 4-PH (ortho,
4.0%) > 5-PH (meta,1.0%), and thereby the relative abundance for
the three ions obeys the same order in the CID–MS spectra, which
was consolidated by analysis of the corresponding energy-resolved
plots (the Supplementary Fig. 3S).
Moreover, significantly different abundance of the product ions
at m/z 122 and m/z 123, formed via migration of the tosyl oxygen,
was obtained in the MS/MS spectra in Fig. 5. As stated previously,
the favorite site in the anilinic ring for the tosyl oxygen trans-
fer follows the order of meta- < ortho- < para- in the CID process
of [1 + H]+. As expected, the relative abundance of the fragment
Fig. 5. The CID–MS spectra of three isomeric p-toluenesulfonyl methylanilines: (a)
[4 + H]+, (b) [5 + H]+ and (c) [6 + H]+

S. Wang et al. / International Journal of Mass Spectrometry 376 (2015) 6–12
11
In addition, it was observed that [6 + H]+ (7.4%) is much more
feasible to undergo fragmentation than the ortho- [4 + H]+ (17.5%)
and the meta-[5 + H]+ (30.0%) isomers under the same CID condi-
tions. These differences have been consolidated by analysis of the
energy-resolved plots (Supplementary Fig. 3S), in which the three
isomers show different main fragment ions with the relative abun-
dance more than 10%: ions at m/z 107 and m/z 123 for [4 + H]+,
ions at m/z 107, m/z 122 and m/z 123 for [5 + H]+, and ions at m/z
107 and m/z 106 for [6 + H]+. As a result, the three isomers can be
differentiated solely based on the tandem MS experiments.
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Acknowledgments
The authors gratefully acknowledge financial support from the
National Science Foundation of China (Nos. 21205025, 21402172).
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Appendix A. Supplementary data
Supplementary material related to this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ijms.2014.11.003.
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