Formation of Pyrylium from Aromatic Systems with a Helium:Oxygen Flowing Atmospheric Pressure Afterglow (FAPA) Plasma Source

Article abstract of DOI:10.1007/s13361-017-1625-z

The effects of oxygen addition on a helium-based flowing atmospheric pressure afterglow (FAPA) ionization source are explored. Small amounts of oxygen doped into the helium discharge gas resulted in an increase in abundance of protonated water clusters by at least three times. A corresponding increase in protonated analyte signal was also observed for small polar analytes, such as methanol and acetone. Meanwhile, most other reagent ions (e.g., O₂ ^+·, NO⁺, etc.) significantly decrease in abundance with even 0.1%?v/v oxygen in the discharge gas. Interestingly, when analytes that contained aromatic constituents were subjected to a He:O₂-FAPA, a unique (M + 3)⁺ ion resulted, while molecular or protonated molecular ions were rarely detected. Exact-mass measurements revealed that these (M + 3)⁺ ions correspond to (M – CH + O)⁺, with the most likely structure being pyrylium. Presence of pyrylium-based ions was further confirmed by tandem mass spectrometry of the (M + 3)⁺ ion compared with that of a commercially available salt. Lastly, rapid and efficient production of pyrylium in the gas phase was used to convert benzene into pyridine. Though this pyrylium-formation reaction has not been shown before, the reaction is rapid and efficient. Potential reactant species, which could lead to pyrylium formation, were determined from reagent-ion mass spectra. Thermodynamic evaluation of reaction pathways was aided by calculation of the formation enthalpy for pyrylium, which was found to be 689.8?kJ/mol. Based on these results, we propose that this reaction is initiated by ionized ozone (O₃ ^+·), proceeds similarly to ozonolysis, and results in the neutral loss of the stable CHO₂ ^· radical. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s13361-017-1625-z

B American Society for Mass Spectrometry, 2017
J. Am. Soc. Mass Spectrom. (2017)
DOI: 10.1007/s13361-017-1625-z
FOCUS: HONORING R. G. COOKS' ELECTION TO THE
NATIONAL ACADEMY OF SCIENCES: RESEARCH ARTICLE
Formation of Pyrylium from Aromatic Systems
with a Helium:Oxygen Flowing Atmospheric
Pressure Afterglow (FAPA) Plasma Source
Sunil P. Badal,1,2 Tyree D. Ratcliff,1 Yi You,2 Curt M. Breneman,1 Jacob T. Shelley1,2
1Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
2Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA
Abstract. The effects of oxygen addition on a helium-based flowing atmospheric
pressure afterglow (FAPA) ionization source are explored. Small amounts of oxygen
doped into the helium discharge gas resulted in an increase in abundance of proton-
ated water clusters by at least three times. A corresponding increase in protonated
analyte signal was also observed for small polar analytes, such as methanol and
acetone. Meanwhile, most other reagent ions (e.g., O2+·, NO+, etc.) significantly
decrease in abundance with even 0.1% v/v oxygen in the discharge gas. Interest-
ingly, when analytes that contained aromatic constituents were subjected to a He:O2-
FAPA, a unique (M + 3)+ ion resulted, while molecular or protonated molecular ions
were rarely detected. Exact-mass measurements revealed that these (M + 3)+ ions
correspond to (M – CH + O)+, with the most likely structure being pyrylium. Presence of pyrylium-based ions was
further confirmed by tandem mass spectrometry of the (M + 3)+ ion compared with that of a commercially
available salt. Lastly, rapid and efficient production of pyrylium in the gas phase was used to convert benzene
into pyridine. Though this pyrylium-formation reaction has not been shown before, the reaction is rapid and
efficient. Potential reactant species, which could lead to pyrylium formation, were determined from reagent-ion
mass spectra. Thermodynamic evaluation of reaction pathways was aided by calculation of the formation
enthalpy for pyrylium, which was found to be 689.8 kJ/mol. Based on these results, we propose that this reaction
is initiated by ionized ozone (O3+·), proceeds similarly to ozonolysis, and results in the neutral loss of the stable
CHO2· radical.
Keywords: Ion–molecule reactions, Ambient mass spectrometry, Pyrylium formation, Mixed-gas plasma, Atmo-
spheric-pressure glow discharge
Received: 27 September 2016/Revised: 6 February 2017/Accepted: 7 February 2017
geometry [5]. Apart from discharge-gas composition, several
other operating parameters of these ionization sources also affect
Introduction
elium is the most commonly used discharge gas in
plasma-based ambient desorption/ionization (ADI)
the plasma characteristics and lead to alternative ionization
pathways. For instance, Cody [8] measured molecular ions for
nonpolar and aliphatic compounds with a direct analysis in real
time (DART) ionization source. The conditions for production
of those spectra were that the grid-electrode potentials were
increased by several hundred volts, the gas-heater temperature
was elevated, and the source was positioned very close
(ca. 3 mm) to the mass-spectrometer inlet. Badal et al. [9]
demonstrated the ability to tune between charge-transfer and
proton-transfer ionization mechanisms simply by changing the
operating parameters of a flowing atmospheric pressure after-
glow (FAPA) ionization source. In that work, it was observed
that charge-transfer ionization was dominant when the
H
sources [1–6] due to the large reaction cross-section of excited
helium species with atmospheric gases, such as N2 and H2O
[7], which lead to greater reagent-ion densities. Several other
gases, such as nitrogen, argon, and air, also have been tested as
plasma gases for ADI sources; however, helium provides the
best sensitivity for most analytes regardless of discharge type or
Electronic supplementary material The online version of this article (doi:10.
1007/s13361-017-1625-z) contains supplementary material, which is available
to authorized users.
Correspondence to: Jacob T. Shelley; e-mail: shellj@rpi.edu

S. P. Badal et al.: Formation of Pyrylium from Aryl Rings with He:O2 FAPA
discharge current was high and helium flow rate was low,
whereas proton-transfer ionization dominated at lower discharge
currents and higher plasma-gas flow rates.
were subjected to a He:O2-FAPA, a unique (M + 3)+ ion was
always produced; it was found that these ions correspond to
(M – CH + O)+. These ions were confirmed to be pyrylium-
based through exact mass and tandem mass spectrometry
measurements. The utility of rapid gas-phase pyrylium-ion
formation is also demonstrated through SN2 chemistry with
ammonia. Lastly, a potential mechanism and likely reactant
species that cause aryl-to-pyrylium conversion will be discussed.
Some groups have explored the utility of mixed gas plasmas
to enhance the sensitivity for different analytes in ADI appli-
cations. For instance, Brewer et al. [10] observed 3-fold and
9-fold increases in molecular-ion signal for naproxen with a
radiofrequency helium:oxygen atmospheric pressure glow
discharge (APGD) source compared with pure helium and pure
argon plasmas, respectively. In addition, they observed
extensive fragmentation of analytes with the mixed-gas APGD,
which produced spectra that were EI-database searchable.
More recently, it has been shown that the addition of low mole
fractions of molecular hydrogen to a helium dielectric-barrier
discharge (DBD) can enhance protonated analyte-ion signal,
(M + H)+, up to 68 times for some analytes without a
corresponding increase in chemical background [11, 12]. These
studies demonstrate the diversity in chemistries that can be
obtained from a range of plasma source configurations; simple
modifications of discharge parameters or doping small amounts
of molecular gases into the discharge can have profound effects
on plasma chemistry and analyte ionization. Here, we explore
the effects of O2 addition on the gas-phase ion chemistry of a
helium FAPA source. The FAPA source, which is based around
a direct current (DC) APGD [4], provides a relatively simple, yet
stable and robust, platform to probe and explore chemistries of
pure and mixed gas plasmas [9, 13].
Experimental
Reagents
All reagents used were analytical grade. Ultra-high purity helium
(99.999%) and a helium/oxygen mixture (80%/20%) were ob-
tained from Airgas (Radnor, PA, USA). Biphenyl was purchased
from ACROS Organics (Morris Plains, NJ, USA), while ben-
zene, 1,3,5-trimethylbenzene, 2,4,6-trimethylpyrylium tetrafluo-
roborate, acetaminophen, and benzene-d6 were purchased from
Sigma-Aldrich (St. Louis, MO, USA).
Ionization Source
The FAPA used here was of a pin-to-plate geometry as de-
scribed by Shelley et al. [18]. Briefly, an atmospheric pressure
glow discharge (APGD) was sustained between a stainless-
steel pin cathode and brass plate anode. The electrodes were
held in place inside a quartz discharge chamber. Discharge
species (e.g., excited species, ions, and electrons) interact with
atmospheric gases and analytes as they exit a 1.6-mm hole in
the anode plate. A high DC potential (ca. - 550 V) was applied
to the pin electrode from a custom-built high-voltage power
supply (Prosolia Inc., Indianapolis, IN, USA), capable of pro-
viding up to 30 mA at - 2000 V. The circuit was completed by
connecting the anode to the ground terminal of the power
supply. The APGD of the FAPA was operated in a current
controlled mode with 20-mA of current. The flow rate of
helium was controlled with a mass flow controller (model
C50L-AL-DD-2-PV2-V0-SCR; Sierra Instruments Inc., Mon-
terey, CA, USA) whereas another mass flow controller (model
C50L-AL-DD-2-PV2-V0-SCR; Sierra Instruments Inc.) was
used to control the flow rate of helium/oxygen mixture. The
gas flows were mixed in a T-junction connected to the dis-
charge chamber. The accuracy and precision of the flow con-
troller used for the helium/oxygen mixture dictated the smallest
fraction of oxygen that could be reproducibly introduced into
the discharge, which was 0.1%. The source was mounted onto
a manual xyz translation stage (PT3; Thorlabs Inc., Newton,
NJ, USA) for precise alignment of the ion source with the mass
spectrometer inlet. Volatile analytes, such as acetone, metha-
nol, and benzene, were introduced to the FAPA afterglow
through a fused-silica capillary with nitrogen as a carrier gas.
Solid analytes were introduced to the FAPA with the glass
probe fixed on a one-dimensional translation stage (PT1;
Thorlabs Inc., Newton, NJ, USA), similar to previous arrange-
ments [19, 20].
Atmospheric-pressure plasmas are well-suited for gas-phase
chemistry as they efficiently produce excited species, ions, and
electrons over a broad range of energies. These species can lead
to unique chemical reactions through ion–molecule and ion–ion
reactions. For example, production of phenol via oxidation of
aromatic systems has commonly been observed with atmospher-
ic pressure chemical ionization (APCI) with a DC corona dis-
charge, though this reaction and the resulting products are com-
monly viewed as a nuisance in mass - spectrometric analyses
[14]. In addition, a number of unique chemical reactions have
been demonstrated with alternating current (AC) dielectric bar-
rier discharges (DBDs). In 2009, Na et al. [15] reported the Birch
reduction of benzene to 1,4-cyclohexadiene with a DBD-based
low-temperature plasma (LTP). They observed dihydrogenation
of benzene and other arenes when introduced to the discharge
region of the LTP. More recently, a single-step nitrogen-atom
insertion between carbon–carbon bonds of saturated alkanes has
+
been shown with gas-phase reactant ions, such as N3 , generated
in microdischarges in nitrogen gas at atmospheric pressure [16].
Furthermore, Zhang et al. [17] observed the replacement of a
carbon atom with a nitrogen atom in the benzene ring via a
reaction with plasma-produced reactants. In this case, the reac-
tion was observed when benzene was introduced directly into
the discharge of an LTP probe operated with air, N2, or even
NO-doped N2 as the discharge gas.
In this work, we show a unique chemical modification of
aromatic systems with an oxygen-doped helium-FAPA (He:O2-
FAPA). Specifically, when aromatic ring-containing analytes

S. P. Badal et al.: Formation of Pyrylium from Aryl Rings with He:O2 FAPA
An electrospray ionization source (HESI-II probe, Thermo
Scientific, San Jose, CA, USA) was used to generate comparison
mass spectra and product ion mass spectra of 2,4,6-
trimethylpyrylium tetrafluoroborate. A 0.4 mM solution of
2,4,6-trimethylpyrylium tetrafluoroborate was prepared in a
methanol:water mixture (50%:50%). The flow rate was set to
5 μL/min. Sheath gas flow rate, sweep gas flow rate, and
auxiliary gas flow rate all were set to zero. The ESI source
voltage was 5.0 kV.
monitored in the low-mass range of the mass spectrum. Most
notably, addition of even a small amount of oxygen to the
discharge increased the abundance of the protonated water
dimer ([H2O]2H+) by 3.4 times (cf. Figure 1) with no notable
elevation in chemical background signals; under certain source
conditions, signal for protonated water dimer increased by
more than 19-fold over a He-FAPA. It is also important to note
that all detected protonated water clusters (i.e., n = 2, 3, 4, and
5) exhibited the same trend upon addition of oxygen to the
FAPA plasma gas (cf. Supplementary Figures S-2 and S-3).
Protonated water clusters are important reagent ions in ADI-
MS analyses as proton-transfer ionization is efficient for many
organic analytes and leads to little molecular fragmentation.
Maximum production of protonated water clusters was found
to occur with 0.1% v/v oxygen in helium (cf. Figure 1, red
trace). A similar increase in signal was also observed for polar
analytes such as acetone (cf. Figure 1, blue trace) and methanol
(cf. Supplementary Figure S-4) with an enhancement in [MH]+
signal of up to 4.5 and 12.5 times, respectively.
Mass Spectrometry
Low resolution and tandem mass spectra were acquired with
Thermo LTQ XL linear ion trap mass spectrometer (Thermo
Scientific, San Jose, CA, USA), while a Thermo Exactive Plus
mass spectrometer (Thermo Scientific, Bremen, Germany) was
used for exact mass measurements. The LTQ XL mass spectra
were collected in positive ionization mode with a maximum
injection time of 100 ms and three microscans per spectrum.
Capillary temperature was maintained at 275 °C. For reagent-
ion measurements, capillary and tube lens voltages were held at
2 and 31 V, respectively, whereas, higher mass-to-charge
detection was done with capillary and tube lens voltages of
15 and 65 V, respectively. High resolution mass spectra were
also collected in positive ionization mode with inlet capillary
temperature, capillary voltage, and S-lens rf level of 320
°C, 0 V, and 50%, respectively.
Though the exact processes that lead to increased protonated
water cluster signals is unknown at this time, some possible
reasons can be deduced from the literature. For instance, it is
known that O2+ can directly lead to the formation of protonated
water clusters via ion–molecule and clustering reactions [24].
Though the conditions used in that study differ from those of a
He:O2-FAPA, the same reactions could occur in the open air
+
afterglow region where plasma species, including O2 , mix
with room air.
Pyrylium Enthalpy Calculations
In contrast to the protonated water clusters, the abundance
of nearly all other FAPA reagent ions, including NO+, HCO+,
and O2+·, dramatically decreased with the smallest fraction of
oxygen added to the discharge gas, 0.1% v/v (cf. Supplementary
Figure S-5). The one exception to this behavior was the ion
signal at m/z 48, which increased by ca. five times with 0.1%
v/v oxygen added to the discharge (cf. Supplementary Figure S-6).
While accurate mass measurements were not possible with
the available instrumentation, the two most likely species to
The enthalpy of formation for pyrylium was determined with
energies derived from ab initio density functional theory (DFT)
calculations. The Becke’s three parameter hybrid DFT/HF
method with Lee-Yang-Parr’s correlation functional (B3LYP)
was used for structural optimization and energy calculation
obtained using Gaussian09. An isodesmic reaction scheme
shown in Supplementary Figure S-1 was used to calculate the
enthalpy of formation for pyrylium. The molecular structures
of benzene, furan, cyclopentadienyl anion, and pyrylium were
prepared using B3lyp/3-21G theoretical model using thermo-
chemical data from the literature [21–23]. An HF/6-31G*
optimization was performed and the resultant geometries and
orbitals were used as the input for geometric optimization and
frequency analysis with B3lyp/6-31+G*, which provided a
zero-point-energy (ZPE) for the isodesmic reaction. The opti-
mized structures were then used to calculate the electronic
energy using B3lyp/6-311++G(d, p). The resulting total ener-
gies were calculated using the sum of the electronic energy and
corrected ZPE, using a correction coefficient of 0.75.
+·
appear at m/z 48 for this system are O3 and (NO + H2O)+.
Results and Discussion
To preliminarily gauge the effects of adding oxygen to a helium
FAPA source, less than 1.0% v/v of oxygen was added to the
helium directly prior to the FAPA discharge. Reagent- and
analyte-ion populations produced with He:O2-FAPA were
Figure 1. Protonated water dimer ([H2O]2H+) (red) and proton-
ated acetone (blue) signals as a function of percent oxygen
composition in the helium-based FAPA

S. P. Badal et al.: Formation of Pyrylium from Aryl Rings with He:O2 FAPA
Because the trend in Supplementary Figure S-6 is much different
results in the removal of CH (or, in this case, CD) from an aryl
ring. The lack of hydrogen atoms in the deuterated pyrylium
product indicates that the mechanism does not involve replace-
ment or removal of aromatic hydrogens, other than the one on
the leaving group.
than that for the NO+, we rationalize that the majority of the ions
detected at this mass are O3+·. This observation is somewhat
+·
surprising given that O3 is known to readily react with O2 to
+·
form O2 [25].
Desorption/ionization of analytes containing aromatic con-
stituents exhibited significant chemical modification of the
aromatic system when a He:O2-FAPA was used. With a
helium-FAPA, these analytes were detected as molecular or
pseudo-molecular ions (M+ or MH+, respectively). When these
analytes were desorbed/ionized with a He:O2-FAPA, all these
species produced a mass spectral peak corresponding to
(M + 3)+ (cf. Figure 2, Supplementary Figures S-7 and S-8).
Exact mass measurements showed that the ion corresponding
to (M + 3)+ from benzene (C6H6) at m/z 81.033 has an
elemental composition of C5H5O+. The most stable and
probable structure for such an elemental composition is that
of pyrylium. Similar to the results obtained with benzene,
(M + 3)+ ions corresponding to (M – CH + O)+ were detected
when biphenyl (C12H10), aniline (C6H7N), acetaminophen
(C8H9NO2), naphthalene (C10H8), anthracene (C14H10), and
1,3,5-trimethylbenzene (C9H12) were introduced to the
He:O2-FAPA, which demonstrates that pyrylium derivatives
can be formed from a variety of aromatic-containing
precursors. Though the finding that aryl rings can be converted
into pyrylium species is surprising, this (M + 3)+ feature has
been shown in APCI mass spectra of benzene produced in air
[14, 26]. Unfortunately, though the mass-spectral peaks are
labeled as C5H5O+, there is no discussion of this ion in the text.
To aid in the confirmation of the formation of pyrylium
from benzene as well as to devise potential reaction
mechanisms, mass spectra of deuterated benzene (C6D6)
were also acquired with a He-FAPA and a He:O2-FAPA
(cf. Figure 3). With a He-FAPA, the molecular cation (M+·),
m/z 84.0842 were detected for deuterated benzene,
whereas (M + 2)+, m/z 86.0650, ions were recorded with a
He:O2-FAPA. Exact mass measurement showed that these
(M + 2)+ ions correspond to (M – CD + O)+ with an elemental
composition of C5D5O+. These findings align with spectra
obtained for previously presented aromatic systems with a
He:O2-FAPA in that a ring-opening – ring-closing reaction
The formation of pyrylium species was further confirmed
via product ion scans of the [M + 3]+ ion of 1,3,
5-trimethylbenzene produced with He:O2-FAPA at m/z 123.
This spectrum was compared with the tandem mass
spectrum obtained from a commercially available 2,4,
6-trimethylpyrylium tetrafluoroborate salt, which was ionized
with electrospray ionization. Both product-ion spectra exhibit-
ed a base peak at m/z 95, corresponding to C6H7O+, as the
major fragment (cf. Figure 4). Furthermore, both spectra
contained minor fragment ions at m/z 93, 105, and 108. The
MS3 spectra of the major fragment ion at m/z 95 were acquired
for both the plasma-synthesized product and the commercial
salt and found to be quite similar with a major fragment at m/z
+
67, corresponding to C5H7 , and minor fragments at m/z 77, 91,
and 93 (cf. Supplementary Figure S-9). The similarity between
mass spectra obtained for the plasma-synthesized product and a
commercial trimethylpyrylium salt, as well as the unique ele-
mental composition of the species formed by He:O2-FAPA,
confirm that pyrylium was formed via the reaction between
aromatic systems and a plasma-generated reactant species.
Based on the results presented above, it is clear that
ring-opening – ring-closing steps must occur to form
pyrylium from the aryl structure. Although at this time
the exact mechanism of pyrylium formation has not been
probed in great detail, some information on the potential
reactants and processes can be inferred from these findings
as well as the literature. First, the reaction occurs very
rapidly and goes to completion on a mass spectrometric
timescale (i.e., tens of milliseconds). As such, the plasma-
produced reactant is almost certainly a positive ion, which
would serve to lower the activation barrier of the reaction
and speed up an otherwise slow reaction. A list of potential
oxygen-containing reactant ions can be formulated from
the background mass spectrum of the He:O2-FAPA
(cf. Supplementary Figure S-10). Potential reactant ions
determined from this mass spectrum include NO+, O2
,
+·
Figure 2. Mass spectra of biphenyl obtained with a He-FAPA (a) and He:O2-FAPA containing 0.1% oxygen (b). Both spectra were
acquired with 1.0 L/min total gas flow rate and 20 mA discharge current

S. P. Badal et al.: Formation of Pyrylium from Aryl Rings with He:O2 FAPA
(a)
(b)
100
+
[M+2]
+
[M+O H]
2
+
[M]
100
+
D O
5
C
+
D
6
5
+
D O H
6 2
C
C
6
6
80
60
40
20
0
80
60
40
20
0
+
D OH
5
C
6
70
80
90
100
m/z
110
120
130
70
80
90
100
m/z
110
120
130
Figure 3. Mass spectra of benzene-D6 obtained with a He-FAPA (a) and He:O2-FAPA with 0.1% oxygen (b). Both spectra were
obtained with 1.0 L/min total gas flow rate and 20 mA discharge current
O3+·, HCO+, and H3O+, which could react with the aro-
matic analyte as shown in Reaction 1:
From the values presented in Table 1, it is clear that ionized
ozone, O3+·, is the most energetically favorable reactant to convert
benzene to pyrylium. However, it is also energetically possible
for NO+ and O2+· to lead to pyrylium-ion formation. A number of
selected ion flow tube (SIFT) MS studies have examined gas-
phase reactions between atmospheric plasma cations, including
NO+ and O2+·, and benzene, toluene, or ethylbenzene [28–30].
The dominant reactions in every case were non-dissociative
charge-transfer ionization, which produced molecular cations
(M+·). In fact, no pyrylium, or any other oxygen-containing
products, were detected in any of those cases. Furthermore, these
charge-transfer reactions were found to proceed at or very near
the collision rate. Thus, it seems unlikely that reactions between
NO+ or O2+· and benzene would lead to pyrylium-ion formation.
Unfortunately, studies on reactions involving O3+·, particu-
larly those with organic molecules, are more sparse. Similar to
NO+ and O2+·, the ionization energy of ozone, 12.53 eV, is
appreciably higher than that of benzene, 9.24 eV, which
indicates that non-dissociative charge-transfer ionization could
be a possible reaction pathway. Perhaps surprisingly, it has
been noted that some exothermic non-dissociative charge-
transfer reactions with ozone ion proceed more slowly
than the collision rate, which implies that other more favorable
reactions pathways exist in these scenarios. Unique behavior of
O3+· has been noted for reactions with smaller, atmospherically
relevant species. For instance, dissociative oxidation products
(cf. Reaction 2) have been observed for species of lower
ionization potential than ozone [31–33]. Theoretical modeling
C6H6 þ ROþðor ROþ⋅Þ→C5H5Oþ þ RCH ðor RCH⋅Þ ð1Þ
where RO+=NO+, O2+·, O3+·, HCO+, or H3O+.
To the best of our knowledge, the standard enthalpy of forma-
tion (ΔHf°) of pyrylium has not been experimentally or computa-
tionally determined. To gain a better understanding of the ener-
getics of the possible reactions taking place, the ΔHf° was calcu-
lated, with density functional theory, from the isodesmic reaction
between pyrylium and the cyclopentadienyl anion (cf. Supple-
mentary Figure S-10). The total energies provided by Gaussian
contain the sum of electronic and thermal enthalpies, which allow
the calculation of the enthalpy of the reaction. The enthalpy of the
reaction is determined by taking the difference of the sum of
reactants and the products. From this approach, the enthalpy of
formation for pyrylium was determined to be 689.8 kJ/mol.
Because benzene has a lower enthalpy of formation than
pyrylium, the pyrylium formation reaction would only proceed
if a stable neutral loss product was formed from the reaction.
Based on the above list of possible reactant ions, the corre-
·
sponding neutral loss products would be HCN, HCO·, HCO2 ,
C2H2, and CH4, respectively. This reaction would only proceed
if the enthalpy of reaction (ΔHrxn°) is negative. Based on the
calculated value of ΔHf° for pyrylium and the literature values
of ΔHf° for all other reactants, Hess’s law was used to calculate
ΔHrxn° for each possible reactant (cf. Table 1).
Figure 4. Tandem MS of [M + 3]+ ion produced from 1,3,5-trimethylbenzene with He:O2-FAPA (0.1% oxygen) (a) and 2,4,6-
trimethylpyrylium with electrospray ionization (ESI) source (b)

S. P. Badal et al.: Formation of Pyrylium from Aryl Rings with He:O2 FAPA
Table 1. Plasma-Generated Reactant Ions and the Corresponding Neutral-Loss Products, along with Their Respective Standard Enthalpies of Formation, which
Could be Responsible for the Conversion of Benzene to Pyrylium. The Standard Enthalpy of Formation for Benzene and Pyrylium is 82.9 kJ/mol [27] and 689.8 kJ/
mol, Respectively
Possible reactant ion
ΔHf, reactant° (kJ/mol)
Neutral-loss product
ΔHf, product° (kJ/mol)
ΔHrxn (kJ/mol)
H3O+
HCO+
NO+
449.2b
824.0a
986.6b
1164b
1352b
CH4
–74.87a
226.73a
135.14a
43.51a
82.8
9.6
–244.6
–513.2
–967.2
C2H2
HCN
HCO·
+·
O2+·
·
O3
HCO2
–221.8b
aValues obtained directly from NIST Webbook [27]
bValues calculated from the data available in NIST webbook [27]
of this reaction revealed that it proceeds through a stable,
although short-lived, five-member ring intermediate.
ketone, acid, or ester) along with a catalyst and suitable solvents
such as acetone and ethers [34]. In addition, the reaction mixture
needs to be refluxed for several hours under high temperatures
[34]. Although synthetic routes for formation of substituted
pyrylium species can have yields as high as 65% [34], synthesis
of pyrylium is a significantly more challenging task due to the
propensity for nucleophilic attack. Here, with a He:O2-FAPA,
conversion of aromatic systems to pyrylium is rapid (within a
few milliseconds), and relatively efficient with a yield of 45%. In
this case, the yield was calculated by dividing the pyrylium ion
signal by all other ion signals related to the aromatic analyte
based on exact mass measurements.
One important use of pyrylium-based compounds is as a
reagent for the synthesis of molecules with strong aromatic
character due to the fact that pyrylium is readily attacked by even
moderate nucleophiles. In particular, pyrylium is often reacted
with ammonia and primary amines to form pyridine and
pyridinium derivatives [37]. Because of their high reactivity via
nucleophilic attack, we explored the ability to create pyridinium
species from plasma-synthesized pyrylium. Specifically, the fast
and efficient production of pyrylium in the gas phase was used to
convert ammonia and benzene into pyridine with He:O2 FAPA.
Ammonia rapidly reacts with pyrylium to produce protonated
pyridine. The abundance of m/z 80, which corresponds to pro-
tonated pyridine, was monitored with continuous introduction of
benzene to the afterglow of He:O2-FAPA. A significant increase
in m/z 80 was observed when ammonia was introduced to the
afterglow (cf. Figure 5), which was not observed with a helium-
only FAPA. Exact mass measurement of m/z 80 produced from
benzene and ammonia with He:O2 FAPA corresponded to the
protonated pyridine, which showed that the pyrylium produced
O3þÁ þ AB→AOþðor AOÞ þ BO2ðor BO2þÞ
ð2Þ
The calculated enthalpies of reactions from Table 1 show that
ozone ion, O3+·, would be the most energetically favorable
reactant ion to convert benzene to pyrylium. To further support
this hypothesis, ion signal at m/z 48 was found to increase by 5-
fold when oxygen was added to the helium-FAPA discharge (cf.
+·
Supplementary Figure S-6); in fact, O3 was the only reagent
ion, other than protonated water clusters, found to increase in
abundance with the addition of oxygen to the plasma gas.
+·
Based on the information above in conjunction with the O3
reaction literature, a possible mechanism for this pyrylium
formation reaction from O3+· is shown in Scheme 1. The first
step of the reaction is similar to ozonolysis of alkenes where a
five-member ring containing three oxygen atoms is formed as
+·
an intermediate. As was shown in the reaction between O3
and SCO [32], the stability of this intermediate would favor
dissociative charge-transfer and lead to a faster reaction rate
than non-dissociative charge-transfer. A ring-opening step,
which leads to separation of oxygen atoms, is followed by a
radical-driven ring closure resulting in the neutral loss of
HCO2˙. Future studies will aim to more systematically study
this reaction pathway, the associated energetics, and the seem-
ingly ubiquitous nature of aryl-to-pyrylium conversion.
Pyrylium-based species have been synthesized in a variety of
fashions and used for diverse applications, particularly as pig-
ments and fluorophores [34–38]. However, pyrylium synthesis
typically requires at least one carbonyl derivative (aldehyde,
-
+
O
+
O
O
O
O
O
+
O
+
O
+
O
O
O
O
+
+
O
-
+
O
O
+
HCO2
O
+
Scheme 1. Likely mechanism of pyrylium formation from benzene with plasma-produced ozone radical ion serving as the other
reactant

S. P. Badal et al.: Formation of Pyrylium from Aryl Rings with He:O2 FAPA
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Figure 5. Chronogram of m/z 80 when benzene was constant-
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introduced in between
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to expand this gas-phase ion chemistry to form more complex
products as well as to scale-up and collect reaction products.
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Conclusion
The effects of oxygen addition to a helium FAPA source were
explored. Unique chemical modification of aromatic systems to
produce pyrylium was observed with He:O2-FAPA. Formation
of pyrylium was confirmed by exact mass measurement, tan-
dem mass spectrometry, and detection of an isotopically la-
beled compound. Furthermore, rapid production of pyrylium
was used to convert benzene to pyridine. Pyrylium rapidly
reacts with primary amines as well. The application of this
method of rapid pyrylium generation could be used for such
amine modifications, which will be the focus of future studies.
The enhancement of protonated water clusters and acetone
on oxygen addition to He-FAPA showed that sensitivity for
different analytes can be enhanced with different gas compo-
sitions. Utility of addition of other molecular gasses to the He-
FAPA will also be studied in future.
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