Methyl group transfer upon gas phase decomposition of protonated methyl benzoate and similar compounds

Article abstract of DOI:10.1002/jms.4069

Gas phase decompositions of protonated methyl benzoate and its conjugates have been studied by using electrospray ionization-collision induced dissociation-tandem mass spectrometry. Loss of CO₂ molecule, thus transfer of methyl group, has been observed. In order to better understand this process, the theoretical calculations have been performed. For methyl benzoate conjugates, it has been found that position of substituent affects the loss of CO₂ molecule, not the electron donor/withdrawing properties of the substituent. Therefore, electrospray ionization-mass spectrometry in positive ion mode may be useful for differentiation of isomers of methyl benzoate conjugates.

Full text of DOI:10.1002/jms.4069

Methyl group transfer upon gas phase decomposition of protonated methyl
benzoate and similar compounds
Rafał Frański*, Błażej Gierczyk, Maciej Zalas, Wojciech Jankowski and Marcin Hoffmann
Adam Mickiewicz University, Faculty of Chemistry, Umultowska 89B, 61-614 Poznań,
Poland;
*
- Author for correspondence, e-mail: franski@amu.edu.pl
Gas phase decompositions of protonated methyl benzoate and its conjugates have been
studied by using electrospray ionization-collision induced dissociation-tandem mass
spectrometry (ESI-CID-MS/MS). Loss of CO molecule, thus transfer of methyl group,
2
has been observed. In order to better understand this process the theoretical
calculations have been performed. For methyl benzoate conjugates, it has been found
that position of substituent affects the loss of CO molecule, not the electron
2
donor/withdrawing properties of the substituent. Therefore ESI-MS in positive ion
mode may be useful for differentiation of isomers of methyl benzoate conjugates.
Keywords: methyl benzoate, electrospray ionization, tandem mass spectrometry, methyl
salicylate, methylparaben
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/jms.4069
This article is protected by copyright. All rights reserved.

Introduction
When upon gas phase decomposition of the given ion, a certain moiety migrates from
one part of the ion to another it may complicate the interpretation of the product ion
spectrum. As a consequence it may hamper the structural elucidations based on the obtained
product ion spectrum. On the other hand, such intramolecular transfers are very interesting
from the gas phase ion chemistry point of view, therefore there is a number of examples of
detailed studies of such processes. The examples involve transfer of such moieties as
[
1]
[2,3]
[4]
[5-7]
[8]
[9]
[10]
[11]
amino, halogen,
methoxy, benzyl,
tosyl, trimethylsilyl, oxygen,
alkyl,
[
12]
[13-20]
hydroxyl and, as expected, most examples involve transfer of methyl group.
Very recently, it has been observed that upon gas phase decomposition of protonated
benzoic acid molecule (and similar compounds) transfer of two protons occurs, which leads
to the formation of protonated benzene molecule. This process has been discussed in details
2
1
by Attygalle and co-workers. In this work we decided to check if upon gas phase
decomposition of protonated methyl benzoate (and its conjugates) the transfer of methyl
group can occur. As demonstrated further, although the methyl group is definitely less prone
to transfer than proton, the process occurs. It also worth adding that the loss of CO molecule
2
has been also observed for metastable methyl benzoate molecular ion (obtained by electron
ionization, EI), however, in the standard EI mass spectra (70 eV) this process has not been
2
2
observed (http://webbook.nist.gov/chemistry/).
Experimental
Methyl benzoate, methyl hydroxybenzoates (all isomers), methyl 2-fluorobenzoate,
methyl 3-fluorobenzoate, phenyl benzoate, methyl 2-naphthoate were obtained from Sigma-
Aldrich (Poznań, Poland) and used without purification.
Methyl 4-fluorobenzoate, methyl 1-naphthoate, methyl 2,6-dimethylbenzoate, methyl
2
,6-dichlorobenzoate, ethyl benzoate and isotope labeled methyl benzoates (C H COOCD
6 5 3
and C D COOCH ) were prepared by esterification of respective acids (acids were obtained
6
5
3
from Sigma-Aldrich). The esterification procedures were as follows: 200 mg of acid was
dissolved in 10 ml of methanol (Sigma-Aldrich). The obtained solution, after addition of 0.5
ml of thionyl chloride was heated under reflux for 1 h and concentrated on a rotary
evaporator. The oily residue was dissolved in 5 ml of ethyl ether (Sigma-Aldrich), washed
three times with saturated sodium bicarbonate (POCh) water solution, dried over anhydrous
sodium sulfate (Chempur) and filtered. After solvent removal by evaporation on a rotary
This article is protected by copyright. All rights reserved.

evaporator the white-yellowish solid product was obtained. To synthesize isotopically
labelled ester C H COOCD the same procedure was used, but the acid, CD OD and thionyl
6
5
3
3
chloride were used in smaller amounts i.e. 100 mg, 3 ml and 0,25 ml, respectively.
In order to synthetize methyl 2,6-dichlorobenzoate, different procedure was used. A
portion of 200 mg of the acid was dissolved in 3 ml of thionyl chloride and stirred for 1 h.
The solution obtained was evaporated on rotary evaporator and a portion of 5 ml of methanol
was then dropwise added to the oily residue and the mixture were heated under reflux for 1 h
and after that the product was isolated using above described procedure.
Product ion spectra were taken on a Waters/Micromass (Manchester, UK) Q-tof
Premier mass spectrometer (software MassLynx V4.1, Manchester, UK). The sample solution
-5
of bilirubin was prepared in methanol/water 3/1 at concentrations about 2x10 mol/L. The
sample solutions were infused into the ESI source by a syringe pump at a flow rate of 5

L/min. The electrospray voltage was 2.7 kV and the cone voltage - 30 V. The source
o
o
temperature was 80 C and the desolvation temperature was 250 C. Nitrogen was used as the
cone gas and desolvating gas at the flow-rates of 0.8 and 13 L/min, respectively. Argon was
used as a collision gas at the flow-rate 0.5 mL/min in the T-wave collision cell. This flow rate
resulted in the collision cell pressure 0.3 Pa. Collision energy (CE, laboratory frame) was 5-
2
0 eV. Only representative examples were selected for presentation, taking into account the
abundances of fragment ions. The applied collision energy, the most important parameter for
CID-MS/MS experiments, is indicated in each product ion spectrum shown. Because of a
wide window (low resolution of the quadrupole analyzer), the selected ion beam and as a
consequence the signals of fragment ions, contained isotope signals. The resolution of the
second analyzer (time of flight analyzer) was 5000 - FWHM definition.
Full geometry optimizations and energy calculations were performed, within DFT
23-25
framework at B3LYP/6-311++G(d,p).
level of theory because B3LYP (Becke, three-
parameter, Lee-Yang-Parr) is one of the most popular functional and can be applied for many
22, 26-27
different systems.
6-311++G(d,p) basis set (augmented with diffuse and polarization
functions) is recommended for calculations for simple molecules that include electronegative
28
29
elements and for comparisons with experiment. Wiberg bond indices were calculated by
3
0, 31
Natural Bond Orbital (NBO) analyse
for bonds between the aromatic or naphthyl ring
and the carboxyl carbon atom. All quantum chemical calculations were performed with
3
2
the GAUSSIAN 09.
This article is protected by copyright. All rights reserved.

Results and Discussion
Figure 1 shows the product ion spectra of protonated methyl benzoate. As shown in
Figure 1, at low collision energy (CE = 7 eV) the most abundant fragment ion is that formed
by CO loss. At higher collision energy this fragment ion is also abundant.
2
FIGURE 1
It can be taken for granted that the loss of CO from protonated methyl benzoate leads to the
2
formation of protonated toluene (m/z 93). In other words, upon gas phase decomposition of
protonated methyl benzoate the transfer of methyl group occurs.
In the product ion spectra shown in Figure 1 there is also a peak at m/z 91, which
3
3
corresponds to the well-known, stable, tropylium (benzylium) ion. The ratio of tropylium
ion/protonated toluene increases with increasing collision energy. At the higher collision
energy there is also the phenylium ion at m/z 77 (Figure 1). It can be assumed that both
tropylium ion and phenylium ion are formed from protonated toluene (by the loss of H and
2
3
4, 35
CH molecule, respectively,
) although their direct formation from protonated methyl
4
benzoate cannot be definitely excluded.
In supporting information there are product ion spectra obtained for deuterium labeled
methyl benzoate (Figures 1s-4s) with brief discussion which confirm the interpretation shown
in Figure 1.
Since the ion under this study is protonated methyl benzoate, thus it is reasonable to
determine the protonation site of methyl benzoate. Our calculations showed that for methyl
benzoate the most energetically favored protonated structure is obtained when the proton
is attached to the oxygen atom of the carboxyl group (Scheme 1). According to results the
structure in which the proton bonded to this oxygen atom is oriented towards the aromatic
ring has lower energy than the structure with proton oriented in the opposite direction
(the latter was of about 2.6 kcal/mol higher in energy).
SCHEME 1
This article is protected by copyright. All rights reserved.

It is reasonable that the first step of the CO loss from protonated methyl benzoate is
2
2
1
analogous to the first step of the CO loss from protonated benzoic acid. Namely, the proton
2
attached to carbonyl oxygen atom is transferred to the ortho position of the aromatic ring
(protonation at ipso position is less favored than protonation at ortho position, Scheme 1). It
is also reasonable that the proton transfer is accompanied by the breaking of the C-C bond
between benzene ring and ester group and then hydrogen is transferred to the ipso position.
…
6
+
3
As a consequence, we deal with formation of the ion-neutral complex C H COOCH .
6
+
Dissociation of this complex leads to the formation of low abundant ion [COOCH ] at m/z
3
+
5
9 (Figure 1) or ion [COOCD ] at m/z 62 (supporting information, Figure 2s and 3s).
3
However, the main process occurring for this complex is the transfer of methyl group to the
benzene ring, the loss of CO molecule, and formation of protonated toluene. Such process
2
should not be affected sterically, therefore should be also observed for protonated methyl 2,6-
dimethylbenzoate. And indeed, as shown in Figure 2, the loss of CO molecule occurs for
2
protonated methyl 2,6-dimethylbenzoate.
FIGURE 2
The product ion spectrum of protonated methyl 2,6-dimethylbenzoate shows that
transfer of methyl group is not sterically affected. However the question is if the process can
be affected by the electron effect and if yes in which way. As shown in Figure 3 the only
process that occurred upon gas phase decomposition of protonated methyl 2,6-
dichlorobenzoate is the formation of benzoyl ion (loss of a methanol molecule). It is clear that
because of the electron effect of chlorine atoms the loss of CO molecule (thus methyl group
2
transfer) does not occur.
FIGURE 3
In order to better understand the electron effect, the product ion spectra were obtained
for protonated methyl benzoate substituted at ortho, meta and para positions by both electron
withdrawing and electron donor substituent. Figure 4 shows the product ion spectra of methyl
fluorobenzoate isomers, while Figure 5 shows the product ion spectra of methyl
hydroxybenzoates isomers. Fluorine is an electron withdrawing substituent and hydroxyl
36
group is and electron donor substituent.
This article is protected by copyright. All rights reserved.

FIGURE 4
FIGURE 5
As clearly shown in Figures 4 and 5, the loss of CO molecule is an efficient process for meta
2
isomers, whereas for ortho and para isomers it is of minor importance. In other words the
position of substituent affects the loss of CO molecule, not the electron donor/withdrawing
2
properties of the substituent. It can be explained on the basis of respective resonance
structures. For ortho and para isomers we can deal with structures containing positive charge
on the substituent and double bond between aromatic ring and carboxyl carbon atom
(
supporting information, Scheme 1s). The loss of CO molecule requires breaking of the bond
2
between the aromatic ring and the carboxyl carbon atom. Formation of the structure for
which this bond is double (thus stronger) prevents the breaking of this bond.
We have also performed the calculations for protonated methyl fluoro- and
hydroxybenzoates conjugates. Analogously as for unsubstituted methyl benzoate, the most
energetically favored protonated structures are those with the proton attached to the oxygen
atom of the carboxyl group (supporting information, Schemes 2s-7s). Furthermore, for the
favored structures, the calculated Wiberg bond indices for bonds between the aromatic ring
and the carboxyl carbon atom, for meta isomers are slightly lower than for ortho and para
isomers (supporting information, Schemes 2s-7s).
It has to be added that besides fluorine and hydroxyl groups other groups can
influence the loss of CO molecule from respective protonated methyl benzoates. In order to
2
minimize other effects than the electron one we have decided to check the influence of
fluorine and hydroxyl moieties. For example, for an amino group, which has stronger electron
3
6
donor properties than a hydroxyl group , we could deal with its protonation instead of
protonation of carbonyl oxygen atom. For a nitro group, which has stronger electron
3
6
withdrawing properties than fluorine , we would deal with its decomposition namely with
3
7
the loss of NO molecule, and this process may compete with the loss of CO molecule.
2
If it is true that that the efficiency of the loss of CO molecule can be explained on the
2
basis of respective resonance structures, for methyl naphthoate isomers we should deal with
different efficiencies of the loss of CO molecule. And indeed, as shown in Figure 6 for
2
methyl 2-naphthoate, the loss of CO molecule is definitely more efficient than for methyl 1-
2
This article is protected by copyright. All rights reserved.

naphthoate. It may be explained on the basis of respective resonance structures (supporting
information, Scheme 8s and 9s).
FIGURE 6
We have also performed the calculations for protonated methyl naphthoates.
Analogously as for the other compounds discussed above, the most energetically favored
structures were obtained when the proton was attached to the oxygen atom of the carboxyl
group (supporting information, Scheme 10s and 11s). Furthermore, for the favored structures,
the calculated Wiberg bond indices for bonds between the naphthyl ring and the carboxyl
carbon atom, for methyl 2-naphthoate are slightly lower than for methyl 1-naphthoate
(supporting information, Scheme 10s and 11s).
We have also checked if the loss of CO molecule can occur for other esters of
2
benzoic acid (other than methyl ester). In other words, we wanted to answer the question if
any other moiety than that of methyl can be transferred to the aromatic ring upon gas phase
decomposition of protonated ester. As shown in supporting information (Figure 5s and 6s),
for protonated ethyl benzoate and protonated phenyl benzoate, the loss of CO molecule does
2
occur. Thus, the moiety other than methyl one are not transferred to the aromatic ring.
Methyl para-hydroxybenzoate has a number of practical applications e.g. as a food
preservative (it is called methylparaben and is coded under the number E218). ESI-MS
coupled with liquid chromatography, usually in negative ion mode, has been used for its
3
8-42
analysis in various samples.
found in various natural sources usually by using electron ionization (EI) mass spectrometry
Methyl ortho-hydroxybenzoate (methyl salicylate) has been
4
3-46
coupled with gas chromatography.
It is worth adding that EI mass spectra of all methyl
hydroxybenzoate isomers are very similar (http://webbook.nist.gov/chemistry/), which may
4
3
cause a problem with their correct identification. As shown in Figure 5, the product ion
spectra of all methyl hydroxybenzoate isomers are substantially different. Therefore ESI-MS
in positive ion mode may be useful for their identification. Obviously it requires more
detailed analytical studies.
Conclusions
The loss of CO molecule, thus transfer of a methyl group, occurs upon gas phase
2
decompositions of protonated methyl benzoate and its conjugates, as demonstrated by the
This article is protected by copyright. All rights reserved.

respective product ion spectra. It is reasonable that this process occurs through the ion-neutral
complex. For methyl benzoate conjugates, it is the substituent position that affects the
process, not its electron donor/withdrawing properties. Therefore, the product ion spectra of
the protonated molecules may be useful for differentiation of isomers of methyl benzoate
conjugates.
Acknowledgments
This research was supported in part by PL-Grid Infrastructure.
References
[
[
[
1] Z.-Y. Ju, Y. Ye, S.-B. Zhong, R.-Y. Zou, X.-C. Liao, Y.-F. Zhao. A novel
n
rearrangement in ESI-MS of spirocyclic pentaerythritol di(phosphate monoamides)
Int. J. Mass Spectrom. 2008, 273, 31.
2] Y. Chai, X. Xiong, L. Yue, Y. Jiang, Y. Pan, X. Fang. Intramolecular halogen transfer
via halonium ion intermediates in the gas phase. J. Am. Soc. Mass Spectrom. 2016,
2
7, 161.
3] N. Picazas-Márquez, M, Sierra, C. Nova, J.M. Moreno, N. Aboitiz, G. de Rivas, M.A.
Sierra, R. Martínez-Álvarez, E. Gómez-Caballero. GC-MS Study of Mono- and
bishaloethylphosphonates related to schedule 2.B.04 of the chemical weapons
convention: the discovery of a new intramolecular halogen transfer. J. Am. Soc. Mass
Spectrom. 2016, 27, 1510.
[
[
[
[
4] Y. Chen, Y. Yin, X. Sun, X. Liu, H. Wang, Y. Zhao. A novel rearrangement in
electrospray ionization multistage tandem mass spectrometry of amino acid ester
cyclohexyl phosphoramidates of AZT. J. Mass Spectrom. 2005, 40, 636.
5] H. Sun, Y. Chai, X. Xu, Y. Pan. Intramolecular benzyl cation transfer in the
fragmentation of Cinchona alkaloid-based quaternary ammonium cations. Int. J. Mass
Spectrom. 2013, 335, 16.
6] F. Li, X. Zhang, H. Zhang, K. Jiang. Gas-phase fragmentation of the protonated
benzyl ester of proline: intramolecular electrophilic substitution versus hydride
transfer. J. Mass Spectrom. 2013, 48, 423.
7] Z. Yan, B. Tounge, G.W. Caldwell. An unusual intramolecular transfer of the
fluorobenzyl cation between two remote amidic nitrogen atoms induced by collision
in the gas phase. Rapid Commun. Mass Spectrom. 2012, 26, 49.
This article is protected by copyright. All rights reserved.

[
[
8] S. Wang, L. Yu, Y. Wu, C. Guo, N. Zhang, K. Jiang. Gas-phase fragmentation of
protonated N,2-diphenyl-N'-(p-toluenesulfonyl)ethanimidamides: tosyl cation transfer
versus proton transfer. J. Am. Soc. Mass Spectrom. 2015, 26, 1428.
9] D. Tsikas. GC–ECNICI-MS/MS of eicosanoids as pentafluorobenzyl-
trimethylsilyl(TMS) derivatives: Evidence of CAD-induced intramolecular
1
8
TMSether-to-ester rearrangement using carboxy- O-labelled eicosanoidsand possible
implications in quantitative analysis. J. Chromatogr. B 2017, 1047, 185.
[
[
[
10]
J. Paulose, J. Cyriac, G. Mathai, D. Giblin, M.L. Gross. Protonated N-alkyl-2-
nitroanilines undergo intramolecular oxidationof the alkyl chain upon collisional
activation. Int. J. Mass Spectrom. 2017, 413, 75.
11]
J.C. Reepmeyer. Direct intramolecular gas-phase transfer reactions during
fragmentation of sildenafil and thiosildenafil analogs in electrospray ionization mass
spectrometry. Rapid Commun. Mass Spectrom. 2009, 23, 927.
12]
L. Svilar, V. Stankov-Jovanovic, M. Stadler, H. Nedev, J.-Cl. Tabet.
Distinctive gas-phase fragmentation pathway of themitorubramines, novel secondary
metabolites from Hypoxylon fragiforme. Rapid Commun. Mass Spectrom. 2012, 26,
2
612.
[
13]
A.-C. Almstrand, C. Johnson, R.C. Murphy. Evidence for an N-methyl transfer
reaction in phosphatidylcholines with a terminal aldehyde during negative
electrospray ionization tandem mass spectrometry. Anal. Bioanal. Chem. 2015, 407,
5
045.
[
[
14]
involving the transfer of a methyl group. J. Mass Spectrom. 2001, 36, 344.
P.R. Tiller, C. Raab, C.E.C.A. HOP. An unusual fragmentation mechanism
15]
L. Yue, C. Guo, Y. Chai, X. Yin, Y. Pan. Gas-phase reaction: alkyl cation
transfer in the dissociation of protonated pyridyl carbamates in mass spectrometry.
Tetrahedron 2014, 70, 9500.
[
[
16]
J. Cui, X. Gao, A. Fan, S. Zhang, Y. Liu, P. Xua, Y. Zhao. Identification of
amino acid phosphorodiamidates of antiviral nucleosides using electrospray ionisation
tandem mass spectrometry. Eur. J. Mass Spectrom. 2011, 17, 187.
17]
X. Gao, G. Zhu, Z. Zeng, W. Chen, Z. Lin, Y. Liu, P. Xu, Y. Zhao. A novel
methyl migration to the phosphoryl group with the formation of cyclic
aminoacylphosphoramidates in electrospray ionization tandem mass spectra of amino
This article is protected by copyright. All rights reserved.

acid ester phosphoramidates of antiviral nucleosides. Rapid Commun. Mass Spectrom.
011, 25, 1061.
18] L. Xiong, L. Ping, B. Yuan, Y. Wang. Methyl group migration during the
2
[
fragmentation of singly charged ions of trimethyllysine-containing peptides:
precaution of using MS/MS of singly charged ions for interrogating peptide
methylation. J. Am. Soc. Mass Spectrom. 2009, 20, 1172.
[
[
[
[
[
19]
X. Zhang, S. Yao, Y. Guo. Intramolecular methyl migration in the protonated
N,N’-dimethylpropane-1,3-diamine and N,N’-dimethylethane-1,2-diamine. Int. J.
Mass Spectrom. 2008, 270, 31.
20]
D.J. Lavorato, L.M. Fell, G.A. McGibbon, S. Sen, J.K. Terlouw, H. Schwarz.
Identifying ylide ions and methyl migrations in the gas phase: the decarbonylation
reactions of simple ionized N-heterocycles. Int. J. Mass Spectrom. 2000, 195/196, 71.
21]
S. Xu, J. Pavlov, A.B. Attygalle. Collision-induced dissociation processes of
protonated benzoic acid and related compounds: competitive generation of protonated
carbon dioxide or protonated benzene. J. Mass Spectrom. 2017, 52, 230.
22]
N. Dechamps, R. Flammang, P. Gerbaux, P.-C. Nam, M.-T. Nguyen.
Decarboxylation of metastable methyl benzoate bolecular ions. J. Am. Soc. Mass
Spectrom. 2006, 17, 807.
23]
P.J. Stephens, F.J. Devlin, C.F. Chabalowski, M.J. Frisch, Ab Initio
calculation of vibrational absorption and circular dichroism spectra using density
functional force fields. J. Phys. Chem. 1994, 98, 11623.
[
[
24]
K. Kim, K.D. Jordan. Comparison of density functional and MP2 calculations
on the water monomer and dimer. J. Phys. Chem. 1994, 98, 10089.
25]
T. Clark, J. Chandrasekhar, G.W. Spitznagel, P.V.R. Schleyer. Efficient
diffuse function-augmented basis sets for anion calculations. III. The 3-21+G basis set
for first-row elements, Li–F. J. Comput. Chem. 1983, 4, 294.
[
[
26]
J. Miao, W. Xu, B. Zhu, Y. Gao, Ti12Xe: A twelve-coordinated Xe-containing
molecule. Phys. Lett. A 2017, 381, 2363.
27]
D.R. Glowacki, W.J. Rodgers, R. Shannon, S.H. Robertson, J.N. Harvey.
Reaction and relaxation at surface hotspots: using molecular dynamics and the
energy-grained master equation to describe diamond etching. Phil. Trans. R. Soc. A
2
017, 375, 20160206.
This article is protected by copyright. All rights reserved.

[
[
28]
orbital methods. XX. A basis set for correlated wave functions. J. Chem. Phys. 1980,
2, 650.
K.B. Wiberg. Application of the pople-santry-segal CNDO method to the
cyclopropylcarbinyl and cyclobutyl cation and to bicyclobutane. Tetrahedron 1968,
4, 1083.
30] J.P. Foster, F. Weinhold. Natural hybrid orbitals. J. Am. Chem. Soc. 1980, 102,
R. Krishnan, J.S. Binkley, R. Seeger, J.A. Pople. Self‐consistent molecular
7
29]
2
[
[
[
7
211.
31]
water dimer. J. Chem. Physics. 1983, 78, 4066.
32]
F. Weinhold, A.E. Reed. Natural bond orbital analysis of near-Hartree-Fock
M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R.
Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, H. Nakatsuji, M.
Caricato, X. Li, H.P. Hratchian, A.F. Izmaylov, J. Bloino, G. Zheng, J.L. Sonnenberg,
M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, T. Vreven, J.A. Montgomery, Jr., J.E. Peralta, F. Ogliaro,
M. Bearpark, J.J. Heyd, E. Brothers, K.N. Kudin, V.N. Staroverov, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M.
Cossi, N. Rega, N.J. Millam, M. Klene, J.E. Knox, J.B. Cross, V. Bakken, C. Adamo,
J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C.
Pomelli, J.W. Ochterski, R.L. Martin, K. Morokuma, V.G. Zakrzewski, G.A. Voth, P.
Salvador, J.J. Dannenberg, S. Dapprich, A.D. Daniels, O. Farkas, J.B. Foresman, J.V.
Ortiz, J. Cioslowski, D.J. Fox. Gaussian 09, Revision A.1, Gaussian, Inc.,
Wallingford, CT, 2009.
[
33]
E.-L. Zins, C. Pepe, D. Rondeau, S. Rochut, N. Gallandc, J.-C. Tabet.
Theoretical and experimental study of tropylium formation from substituted
benzylpyridinium species J. Mass. Spectrom. 2009, 44, 12.
[
34]
D. Schröder, H. Schwarz, P. Milko, J. Roithová. Dissociation routes of
protonated toluene probed by infrared spectroscopy in the gas Phase. J. Phys. Chem. A
2
006, 110, 8346.
O. Dopfer, J. Lemaire, P. Maître, B. Chiavarino, M.E. Crestoni, S. Fornarini.
[
35]
IR spectroscopy of protonated toluene: Probing ring hydrogen shifts in gaseous
arenium ions. Int. J. Mass Spectrom. 2006, 249-250, 149.
This article is protected by copyright. All rights reserved.

[
[
36]
C. Hansch, A. Leo, R.W. Taft. A survey of hammett substituent constants and
resonance and field parameters. Chem. Rev. 1991, 97, 165.
37]
K. Levsen, H.-M. Schiebel, J.K. Terlouw, K.J. Jobst, M. Elend, A. Preiß, H.
Thiele, A. Ingendoh. Even-electron ions: a systematic study of the neutral species lost
in the dissociation of quasi-molecular ions. J. Mass Spectrom. 2007, 42, 1024.
[
[
38]
J. Lv, L. Wang, X. Hu, Z. Ta, Y. Yang. Rapid determination of 10 parabens in
spices by high performance liquid chromatography-mass spectrometry. Anal. Lett.
2
012, 45, 1960.
I. González-Mariño, J.B. Quintana, I. Rodríguez, R. Cela. Simultaneous
39]
determination of parabens, triclosan and triclocarban in water by liquid
chromatography/ electrospray ionisation tandem mass spectrometry. Rapid Commun.
Mass Spectrom. 2009, 23, 1756.
[
[
40]
S. Lu, S. Gong, S. Ma, X. Zeng, Z. Yu, G. Sheng, J. Fu. Determination of
parabens in human urine by liquid chromatography coupled with electrospray
ionization tandem mass spectrometry. Anal. Methods. 2014, 6, 5566.
41]
R. Rodríguez-Gómez, N. Dorival-García, A. Zafra-Gómez, F.J. Camino-
Sánchez, O. Ballesteros, A. Navalón. New method for the determination of parabens
and bisphenol A inhuman milk samples using ultrasound-assisted extraction andclean-
up with dispersive sorbents prior to UHPLC–MS/MS analysis. J. Chromatogr. B
2
015, 992, 47.
[
[
[
42] L. Ren. J. Fang, G. Liu, J. Zhang, Z. Zhu, H. Liu, K. Lin, H. Zhang, S. Lu.
Simultaneous determination of urinary parabens, bisphenol A, triclosan, and 8-
hydroxy-2′-deoxyguanosine by liquid chromatography coupled with electrospray
ionization tandem mass spectrometry. Anal. Bioanal. Chem. 2016, 408, 2621.
43]
T.K. Jayasekara, P.C. Stevenson, S.R. Belmain, D.I. Farman D.R. Hall.
Identification of methyl salicylate as the principal volatile component in the methanol
extract of root bark of Securidaca longepedunculata Fers. J. Mass Spectrom. 2002,
3
7, 577.
Y. Kuwahara, M. Morita, Y. Ichiki, T. Tanabe, Y. Asano. 1-Phenyl-2-
44]
pentanone and methyl salicylate: new defense allomone components and their content
shift during ontogenetic development of the millipede Nedyopus tambanus
mangaesinus (Polydesmida: Paradoxosomatidae). Appl. Entomol. Zool. 2017, 52, 447.
This article is protected by copyright. All rights reserved.

[
[
45]
R.H.C. Nébié, R.T. Yaméogo, A. Bélanger, F.S. Sib. Salicylate de méthyle,
constituant unique de l’huile essentielle de l’écorce des racines de Securidaca
longepedunculata du Burkina Faso. C. R. Chimie 2004, 7, 1003.
46]
C. Deng, X. Zhang, W. Zhu, J. Qian. Gas chromatography-mass spectrometry
with solid-phase microextraction method for determination of methyl salicylate and
other volatile compounds in leaves of Lycopersicon esculentum. Anal. Bioanal. Chem.
2
004, 378, 518.
This article is protected by copyright. All rights reserved.

H
H
O
O
O
O
+
C
+
C
CH3
CH3
CH3
+
O
O
H
A
E = 0.0 kcal/mol
E = 2.6 kcal/mol
O
18.4 kcal/mol
O
O
O
H
CH3
CH3
+
C
CH3
O
+
C
O
CH3
O
H
O
H
H
+
HC
+
HC
H
H
H
E = 24.4 kcal/mol
E=24.3 kcal/mo
E = 25.4 kcal/mol
E = 28.3 kcal/mol
Scheme 1. Investigated types of protonation patterns of methyl benzoate.
A
E - relative energy, - absolute energy baseline: -460.593103 [hartree].
This article is protected by copyright. All rights reserved.

Figure 1. Product ion spectra of protonated methyl benzoate.
This article is protected by copyright. All rights reserved.

Figure 2. Product ion spectrum of protonated methyl 2,6-dimethylbenzoate.
This article is protected by copyright. All rights reserved.

Figure 3. Product ion spectrum of protonated methyl 2,6-chlorobenzoate.
This article is protected by copyright. All rights reserved.

Figure 4. Product ion spectra of protonated methyl fluorobenzoates isomers.
This article is protected by copyright. All rights reserved.

Figure 5. Product ion spectra of protonated methyl hydroxybenzoates isomers.
This article is protected by copyright. All rights reserved.

Figure 6. Product ion spectra of protonated methyl naphthoate isomers.
This article is protected by copyright. All rights reserved.