Mass spectral study of the CWC-related S-alkyl methylphosphonochloridothioites/S,S′-dialkyl (alkyl′)methylphosphonodithioites under gas chromatography-mass spectrometry conditions

Article abstract of DOI:10.1016/j.ijms.2015.12.004

A class of S-alkyl methylphosphonochloridothioites 3 (11 compounds), S,S′-dialkyl methylphosphonodithioites 4 (12 compounds) and S-alkyl S′-alkyl′ methylphosphonodithioites 5 (9 compounds) were synthesized and were analyzed using gas chromatography-electron ionization mass spectrometer (GC-EIMS). Generalized fragmentation pathways under experimental condition for synthesized compounds are proposed based on analysis of fragment ions of deuterated analogs and density functional theory (DFT) calculations. Results of the study were undertaken with a view to enrich the Organization for the Prohibition of Chemical Weapons (OPCW) Central Analytical Database (OCAD), which may be used for detection and identification of Chemical Weapons Convention (CWC)-related chemicals during on-site inspection and/or off-site analysis, such as OPCW proficiency tests.

Full text of DOI:10.1016/j.ijms.2015.12.004

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Contents lists available at ScienceDirect
International Journal of Mass Spectrometry
journal homepage: www.elsevier.com/locate/ijms
Mass spectral study of the CWC-related S-alkyl
ꢀ
methylphosphonochloridothioites/S,S -dialkyl
ꢀ
(
alkyl )methylphosphonodithioites under gas chromatography–mass
spectrometry conditions
a,∗
c
b,c
b
Hamid Saeidian , Valiollah Mirkhani , Sajjad Mousavi Faraz , Mansour Sarabadani ,
b
b
d
b,∗
Mohammad Taghi Naseri , Davood Ashrafi , Zohreh Mirjafary , Mehran Babri
Department of Science, Payame Noor University (PNU), P.O Box: 19395-4697, Tehran, Iran
Defense Chemical Research Lab (DCRL), P.O. Box: 31585-1461, Karaj, Iran
Department of Chemistry, University of Isfahan, P.O Box: 81746-73441, Isfahan, Iran
a
b
c
d
Department of Chemistry, Tehran Science and Research Branch, Islamic Azad University, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
ꢀ
A class of S-alkyl methylphosphonochloridothioites 3 (11 compounds), S,S -dialkyl methylphospho-
nodithioites 4 (12 compounds) and S-alkyl S -alkyl methylphosphonodithioites 5 (9 compounds) were
synthesized and were analyzed using gas chromatography–electron ionization mass spectrometer
Article history:
Received 10 October 2015
Received in revised form 7 December 2015
Accepted 11 December 2015
Available online xxx
ꢀ
ꢀ
(GC–EIMS). Generalized fragmentation pathways under experimental condition for synthesized com-
pounds are proposed based on analysis of fragment ions of deuterated analogs and density functional
theory (DFT) calculations. Results of the study were undertaken with a view to enrich the Organization
for the Prohibition of Chemical Weapons (OPCW) Central Analytical Database (OCAD), which may be
used for detection and identification of Chemical Weapons Convention (CWC)-related chemicals during
on-site inspection and/or off-site analysis, such as OPCW proficiency tests.
Keywords:
Electron ionization mass spectrometry
Density functional theory
CWC-related chemicals
Symbiosis
© 2015 Elsevier B.V. All rights reserved.
HSAB concept
1
. Introduction
Chemical warfare agents analysis is an important part of veri-
fication activities according to CWC [4]. The Organization for the
Among chemical weapons, Organophosphorus nerve agents
OPNA) constitute the greatest concern due to their high toxic
Prohibition of Chemical Weapons (OPCW) maintains a network
of designated laboratories in order to provide off-site analytical
services [5]. A great deal of attention has been focused on the devel-
opment of analytical techniques for the rapid and unambiguous
identification of chemical warfare agents (CWAs), their precursors,
reaction, and degradation products. Gas chromatograph (GC) cou-
pled with mass spectrometer (MS) is widely used for the analysis of
CWAs, because most CWAs are volatile and nonpolar compounds
[6–10]. On the other hand, GC–MS instrument has been exten-
sively used due to its high sensitivity, reliability, and versatility
[11]. GC–MS analysis is generally performed using electron ion-
ization (EI). This system provides extensive structural hints about
the chemical through its characteristic fragmentation pathways. On
the other hand, EI mass spectra of many CWC-related chemicals are
available in the OPCW Central Analytical Database (OCAD) [12]. For
unequivocal identification of CWC-related compounds in real sam-
ples or OPCW proficiency tests, the availability of mass spectra and
interpretation skills are essential requirements. Millions of chemi-
cals are listed in CWC annex of chemicals in three distinct schedules.
(
effects on humans; even low levels of exposure can cause muscle
twitching, miosis, hyperglycemia, and ultrasecretions, convulsions,
seizures, and death of the individual [1]. The high toxicity of these
agents can be attributed to the excessive cholinergic stimulation
caused by inhibition of acetylcholinesterase (AChE) [2]. One AChE
molecule can efficiently hydrolyze around 25,000 molecules of ACh
per second. It is not present in very large amounts in the human
body, so blocking of the enzyme quickly leads to fatal consequences.
The OPNAs, such as sarin, soman, VX, and tabun, were used for the
first time during the Iran–Iraq war and subsequently in some ter-
rorist attacks in Japan [3]. Chemical warfare agents are still a threat,
and based on CWC, the international community should work to
achieve a world free of such weapons of mass destruction.
∗ Corresponding author. Tel.: +98 66534916.
E-mail address: Saeidian1980@gmail.com (H. Saeidian).
http://dx.doi.org/10.1016/j.ijms.2015.12.004
1
387-3806/© 2015 Elsevier B.V. All rights reserved.
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H. Saeidian et al. / International Journal of Mass Spectrometry xxx (2015) xxx–xxx
Scheme 1. Microsynthesis route of the studied compounds 3, 4, and 5.
It is impossible to have a complete collection of GC–MS data for
all CWC-related compounds due to millions of possibilities. S-alkyl
frequency calculations, zero-point energies (ZPEs) and thermal cor-
rections were obtained at 298 K.
ꢀ
methylphosphonochloridothioites 3, S,S -dialkyl methylphospho-
ꢀ
ꢀ
nodithioites 4, and S-alkyl S -alkyl methylphosphonodithioites 5
are covered under CWC schedule 2.B.04, as well as other com-
pounds with phosphorus bonded to methyl, ethyl, isopropyl, or
propyl moieties. Currently, there is no mass spectrum for such
chemicals in commercial databases and OCAD. Therefore, we have
focused on the EI mass spectral characterization of them through
possible fragmentation pathways based on data from analysis of
fragment ions of deuterated analogs, and energy calculations.
2
.4. General procedure for microsynthesis of S-alkyl
ꢀ
methylphosphonochloridothioites 3, S,S -dialkyl
methylphosphonodithioites 4, and S-alkyl S -alkyl
ꢀ
ꢀ
methylphosphonodithioites 5
The corresponding S-alkyl methylphosphonochloridothioites 3
were synthesized by the controlled addition of RSH to methylphos-
phine dichloride solution. The appropriate thiol (0.30 mmol) and
triethylamine or pyridine (0.65 mmol) in dichloromethane (200 ␮L)
2
. Experimental
were added slowly into the solution of methylphosphine dichloride
◦
(
0.25 mmol) in dichloromethane (500 ␮L), while stirring at 0–5 C.
2.1. Reagents and chemicals
After 15 min, the resulting precipitate was filtered off and the solu-
tion was analyzed using GC–MS (Scheme 1).
All chemicals required for the microsynthesis of S-alkyl
The more addition of RSH (RꢀSH) to the solution of S-alkyl
ꢀ
methylphosphonochloridothioites 3, S,S -dialkyl methylphospho-
methylphosphonochloridothioites 3 was afforded the desired
ꢀ
ꢀ
ꢀ
nodithioites 4, and S-alkyl S -alkyl methylphosphonodithioites 5
products of S,S -dialkyl methylphosphonodithioites 4 and S-alkyl
were purchased from Sigma–Aldrich (St. Louis, MO, USA), Fluka
Neu-Ulm, Germany), and Merck (Darmstadt, Germany), and were
used as received. Methylphosphine dichloride 2 was synthesized
using existing method (Scheme 1) [13].
Sꢀ-alkylꢀ methylphosphonodithioites 5. Solution RSH or RꢀSH
(
(0.30 mmol) in dichloromethane (200 ␮L) was slowly added into
the S-alkyl methylphosphonochloridothioites 3 solution and the
resulted mixture was allowed to stir at 0–5 ◦C for 1 h. Any precipi-
tate was filtered off and the solutions were analyzed using GC–MS,
as required (Scheme 1).
2.2. GC–MS analyses
It should be noted that the separation and purification of CWC-
related chemicals, due to the extreme toxicity of these materials,
are very difficult and, therefore, should be handled only by a trained
professional in an efficient fume cupboard equipped with active
charcoal filtration system.
The GC–MS analyses were performed using an Agilent 6890N
gas chromatograph coupled to a 5973 Mass Selective Detec-
tor, a HP-5MS capillary column (30 m, 320 ␮m i.d. and 0.25 ␮m
film thickness), and helium as carrier gas at constant flow at
−
1
◦
1
.8 mL min . The oven’s temperature was set at 40 C for 3 min
◦
◦
and then it was increased to 280 C with ramp of 10 C/min and
3. Results and discussion
◦
held at 280 C for 6 min. The samples were injected in splitless mode
at an injection temperature of 250 C. The temperatures of the EI
◦
3.1. Synthesis
◦
source and analyzer were kept at 230 and 150 C, respectively. The
scan range was m/z 35–500. Automated mass spectral deconvo-
lution and identification system (AMDIS) software [14] was used
to calculate retention indices of the synthesized compounds. An
The microsynthesis of products 4 and 5 generally involves
two steps: the initial addition of the corresponding thiol to
methyldichlorophosphine 2 in the presence of triethylamine or
pyridine, to form S-alkyl methylphosphonochloridothioites 3, and
alkane mixture [octane (C ) to tetracosane (C24)] was used for the
8
retention index calculation [15].
ꢀ
subsequently, more addition of RSH (R SH) to the solution of S-
alkyl methylphosphonochloridothioites 3 to yield desired products
4 and 5. Using CD I instead of CH I in Scheme 1 afforded deuterated
2.3. Computational details
3
3
analogs of 3, 4, and 5 (Tables 1–3).
Geometry optimizations and frequency calculations for all
It should be noted that the corresponding methylphosphinoth-
ioates or methylphosphonodithioates as by-products are also
observed with low yields in the crude of the reaction, while
species were carried out using the Gaussian 03 program [16]. DFT
with the Becke three parameters hybrid functional (DFT-B3LYP)
calculations were performed with a 6-311++G (2d, 2p) basis set
for all atoms. Vibrational frequencies were calculated at the same
level to ensure that each stationary point was a real minimum.
Harmonic-oscillator approximation was also used for the ther-
modynamic partition functions. After geometry optimization and
ꢀ
all attempts for the synthesis of corresponding O-O -dialkyl
methylphosphonites were failed and often produced O-alkyl
methylphosphinates and methylphosphonates as main products
ꢀ
[17]. High affinity of O-O -dialkyl methylphosphonites to oxida-
tion can be described by symbiosis effect. The term “symbiosis” is
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Table 1
GC/MS data of S-alkyl methylphosphonochloridothioites 3.
Entry
R
Retention
index (RI)
M+
•
Fragment ions (% relative abundances)
[A]
[B]
[C]
[D]
[E]
[F]
[G]
[H]
[I]
1
Et
957
952
142 (100)
44 (36)
145 (100)
47 (36)
156 (49)
58 (18)
156 (52)
58 (19)
159 (51)
61 (20)
170 (27)
72 (10)
170 (54)
72 (20)
173 (51)
72 (19)
184 (3)
86 (1)
187 (3)
89 (1)
198 (1)
00 (1)
127 (16)
129 (6)
127 (12)
129 (6)
141 (1)
143 (–)
141 (1)
143 (–)
144 (1)
147 (–)
155 (1)
157 (–)
155 (1)
157 (–)
158 (1)
159 (–)
–
114 (97)
116 (35)
117 (93)
119 (34)
114 (100)
116 (37)
114 (100)
116 (37)
117 (100)
119 (35)
114 (100)
116 (37)
114 (100)
116 (37)
117 (100)
119 (38)
114 (87)
116 (33)
117 (86)
119 (33)
114 (51)
116 (100)
113 (43)
115 (18)
116 (43)
118 (17)
113 (13)
115 (36)
113 (7)
115 (9)
116 (8)
118 (9)
113 (16)
115 (58)
113 (10)
115 (42)
116 (112)
118 (44)
113 (18)
115 (58)
116 (18)
118 (59)
113 (11)
115 (45)
107 (36)
109 (2)
110 (38)
112 (2)
121 (23)
123 (1)
121 (19)
123 (1)
124 (20)
126 (1)
135 (22)
137 (1)
135 (16)
137 (1)
138 (19)
140 (1)
149 (23)
151 (1)
152 (25)
154 (1)
163 (12)
165 (1)
79 (26)
81 (14)
82 (20)
84 (14)
79 (31)
81 (13)
79 (27)
81 (7)
82 (26)
84 (7)
79 (17)
81 (14)
79 (21)
81 (9)
82 (20)
84 (10)
79 (12)
81 (17)
82 (11)
84 (17)
79 (6)
81 (14)
83 (4)
84 (14)
86 (4)
81 (13)
83 (4)
81 (7)
83 (2)
84 (7)
86 (2)
81 (14)
83 (4)
81 (9)
83 (3)
84 (10)
86 (3)
81 (17)
83 (5)
84 (18)
86 (6)
81 (10)
83 (1)
99 (23)
101 (9)
99 (21)
101 (8)
99 (9)
101 (3)
99 (9)
101 (3)
99 (9)
101 (3)
99 (6)
101 (5)
99 (5)
101 (6)
102 (1)
14 (5)
127 (16)
129 (6)
130 (1)
132 (–)
127 (2)
129 (1)
–
127 (16)
129 (6)
130 (1)
132 (–)
141 (1)
143 (–)
141 (1)
143 (–)
144 (1)
146 (–)
155 (1)
157 (–)
155 (1)
157 (–)
158 (5)
160 (–)
169 (–)
171 (–)
172 (–)
173 (–)
183 (–)
185 (–)
1
2a
3
Et
1
n-Pr
i-Pr
1055
999
1
4
1
5a
6
i-Pr
886
–
1
n-Bu
sec-Bu
sec-Bu
n-Pen
n-Pen
n-Hex
1156
1107
1102
1253
1250
1360
127 (3)
129 (1)
–
1
7
1
8a
9
–
1
99 (5)
101 (2)
99 (4)
101 (2)
99 (2)
101 (7)
127 (4)
129 (2)
130 (5)
132 (2)
127 (2)
129 (1)
1
1
1
0a
1
–
–
1
2
81 (10)
a
S-alkyl methyl(d3)phosphonochloridothioites 3.
Table 2
GC/MS data of S,S -dialkyl methylphosphonodithioites 4.
ꢀ
M+
•
Fragment ions (% relative abundances)
Entry
R
Retention
index (RI)
[A]
[B]
[C]
[D]
[E]
[F]
[G]
1
2
Et
Et
n-Pr
n-Pr
1200
1197
1380
1378
1271
1572
1464
1467
1463
1782
1769
1973
168(86)
171(91)
196(65)
199(59)
196(71)
224(59)
227(42)
224(45)
227(44)
252(21)
255(20)
280(11)
153(15)
153(15)
181(8)
181(7)
181(2)
209(5)
209(<1)
209(1)
209(1)
237(2)
237(2)
265(1)
139(61)
142(62)
153(19)
156(17)
153(29)
167(16)
170(12)
167(13)
170(13)
181(8)
140(43)
143(45)
154(78)
157(73)
154(36)
168(50)
171(43)
168(45)
171(43)
182(7)
125(7)
125(6)
139(17)
139(16)
139(5)
153(12)
153(2)
153(3)
153(2)
167(5)
167(5)
182(1)
111(100)
112(14)
115(15)
112(79)
115(84)
112(69)
112(100)
115(100)
112(100)
115(100)
112(56)
115(55)
112(38)
107(10)
110(10)
121(10)
124(10)
121(5)
135(13)
138(4)
135(4)
a
114(100)
111(100)
114(100)
111(100)
111(85)
114(68)
111(66)
114(67)
111(40)
114(38)
111(18)
3
4
a
5
6
7
i-Pr
n-Bu
n-Bu
sec-Bu
sec-Bu
n-Pen
n-Pen
n-Hex
a
8
9
a
138(4)
1
1
1
0
1
2
149(12)
152(12)
164(2)
a
184(7)
195(5)
185(7)
196(3)
a
ꢀ
S,S -dialkyl methyl(d3)phosphonodithioites 4.
applied to explain the phenomenon of maximum flocking of either
hard or soft substitutions in the same molecules [18].
As expected, RI of compounds containing branched alkyl groups
were less than those of compounds containing normal alkyl groups.
Deuterosubstitution can affect analyte evaporation, diffusion, and
partition properties, affecting molecular interactions with the GC
stationary phase. In general, compounds 3, 4, and 5 have higher RI
than their corresponding deuterated analogs (Tables 1–3).
3.2. GC–MS analyses
The molecular ion (M+ ) of S-alkyl methylphosphonochloridoth-
ioites 3 is observed in their EI–MS spectra with relative good to
moderate abundance. The base peak in EI–MS of chemicals bearing
•
Major EI fragment ions of S-alkyl methylphosphonochloridoth-
ioites 3, as well as their retention indices (RI), are given in Table 1,
and the plausible fragmentation routes of 3 are shown in Fig. 1.
Table 3
ꢀ
ꢀ
GC/MS data of S-alkyl S -alkyl methylphosphonodithioites 5.
ꢀ
+•
Entry
R
R
Retention
index (RI)
M
Fragment ions (% relative abundances)
ꢀ
ꢀ
ꢀ
ꢀ
[A]
[B]/[B ]
[C]/[C ]
[D/[D ]
[E]
[F]
[G]/[G ]
1
2
Et
Et
Et
Et
Et
Et
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
sec-Bu
n-Bu
n-Pen
n-Pen
sec-Bu
sec-Bu
n-Pen
1287
1283
1330
1327
1498
1492
1424
1421
1581
182(63)
185(70)
196(73)
199(69)
210(41)
213(43)
210(38)
213(45)
224(36)
167(8)
167(9)
181(1)
181(1)
195(7)
195(6)
195(<1)
195(–)
209 (5)
139 (22)/153 (10)
142 (23)/156 (10)
139 (280)/167 (2)
142 (27)/170 (2)
139 (33)/181 (7)
142 (32)/184 (7)
153 (11)/167 (2)
156 (12)/170 (2)
153 (12)/181 (5)
140 (69)/154 (4)
143 (76)/157 (4)
140 (89)/168 (2)
143 (84)/171 (2)
140 (72)/182 (1)
143 (75)/185 (1)
154 (32)/168 (15)
157 (34)/171 (16)
154 (32)/182 (7)
125 (21)/138 (–)
125 (20)/138 (–)
125 (21)/153 (–)
125 (18)/153 (–)
125 (26)/167 (–)
125 (24)/167 (–)
139 (8)/153 (11)
139 (8)/153 (–)
139 (12)/167 (2)
111(100)
114(100)
111(85)
114(84)
111(100)
114(100)
111(61)
114(61)
111(81)
112(41)
115(45)
112(100)
115(100)
112(84)
115(88)
112(100)
115(100)
112(100)
107 (9)/121 (4)
110 (8)/124 (4)
107 (22)/135 (2)
110 (22)/138 (–)
107 (18)/149 (7)
110 (17)/152 (7)
121 (6)/135 (2)
124 (6)/138 (2)
121 (8)/149 (7)
a
3
4
a
5
6
a
7
8
a
9
a
ꢀ
ꢀ
S-alkyl S -alkyl methyl(d3)phosphonodithioites 5.
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4
Cl
SR
P
3
CH
3
-
Cl
-CH3
(R-H)
if R = n-alkyl
-
CH
3
-CH
3
-
(R-H)
SH
-R
-Cl
-SR
-
(R-H)
-
n
Cl
S
R'
RS
Cl
RS
HS
Cl
HS
Cl
S
Cl
S
P
P
CH
3
PSCl
P
P
P
P
P
-
(R-H)
P
P
CH
3
CH
3
CH
CH
3
CH
3
Cl
Cl
3
CH
3
CH3
I (n-alkyl)
A
B
C
D
E
F
G
H
I(sec-alkyl)
-
Cl
-SH
-
CH2
Fig. 1. Proposed fragmentation routes for S-alkyl methylphosphonochloridothioites 3.
ethyl substitution on sulfur atom is M+• (Table 1, entry 1 and 2).
the base peak or the second highest peak in the EI–MS spectra of 3
resulted from loss of an alkene molecule from M through 1,3 C-S
+
•
+•
When the S-alkyl chain length increases, the M signal decreases
in intensity. Expected isotopic ratios of chlorine and sulfur con-
taining fragments were observed, as is evident from the relative
abundances listed in Table 1.
Fragment ion [A] is formed through ␣-cleavage of CH3 P bond.
The ion at m/z 127 in the EI mass spectrum of deuterated analog of
hydrogen shift as depicted in Scheme 2. Analysis of mass spectra of
deuterated analogs also supported this point (Fig. 2).
Direct expulsion of alkyl on sulfur from M+ led to the forma-
tion of fragment ion [C] at m/z 113. Spectra of deuterated analogs
(Table 1, entry 2, 5, 8, and 10) revealed the ion corresponding to this
fragmentation at m/z 116. It should be noted that ion [C] could be
related to three possible structures (Scheme 3). The DFT calculated
•
S-ethyl methyl(d )phosphonochloridothioites (Table 1, entry 2) is
3
the result of elimination of CD3 from M+ via ␣-cleavage. Ion [B] as
•
Fig. 2. Representative EI–MS mass spectra of 3 and its deuterated analog.
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(
R')RS
SH
P
C/C'
HS
S
-
R(R
')
CH3
P
r
o
-H)
HS
SH
R
(
)
-
P
'-
H
CH3
E
R
(
-
F
CH3
'
)
R
(
R
-
S
P
R = R', 4
R
R', 5
RS
SR'
-R(R')
P
(R')RS
CH3
B/B'
CH3
CH3
SR(R)
P
HS
G/G'
-
CH2
P
CH3
D/D'
-
(R
-H) o
SR(R')
r -(
R'-H
)
RS
P
SR'
A
ꢀ
ꢀ
ꢀ
Fig. 3. Proposed fragmentation routes for S,S -dialkyl methylphosphonodithioites 4 and S-alkyl S -alkyl methylphosphonodithioites 5.
7
9 as [E]. When the S-alkyl chain length increases, the [E] signal
decreases in intensity. Fragment ion [G] was observed in EI–MS
of all S-alkyl methylphosphonochloridothioites 3 with relative low
intensity. The characteristic ion [H] was observed in EI–MS spec-
trum of chemical 3 that is bearing n-alkyl group on sulfur. Loss of
•
R
[
as an alkyl radical from S-(n-alkyl) chain gave rise to fragment
n−1
H]. This peak can be used for unambiguous distinction of n-alkyl
Scheme 2. Proposed fragmentation pathway for formation of [B].
from sec-alkyl group in such compounds. It is interesting to note
that the leaving of a methyl radical from alkyl on sulfur atom led
to the formation of fragment ion [M+ −15] as [I] with relative low
intensity. In case of sec-alkyl, structure of the ion [I] is a sulfonium
fragment, while in case of n-alkyl, it is a cyclic chloronium fragment.
The corresponding fragment ions [I] in EI–MS spectra of deuterated
analogs are also observed.
It is noteworthy that in EI–MS spectra of chemicals bearing large
alkyl (R ≥ 4) on sulfur atom, elimination of this alkyl as a thioalde-
hyde or thioketone by hydrogen migration and direct elimination
•
free energy of the structures (b) and (c) are equal. Free energy of
−
1
the structure (a) was calculated to be 151 kJ mol higher than the
structures (b) and (c). Fragment ion (a) is an unstable ion due to its
angel strain [19]. This indicated that the cleavage of the S R bond
initiated from chlorine (a) is not preferred over that the process
initiated from phosphorous (b) or sulfur (c).
•
Elimination of chlorine radical and RS from EI–MS of 3 led to
the formation of fragment ions [D] and [F], respectively with rel-
ative moderate abundance. Concerted or step-wise expulsion of
•
+•
of RS from fragment ion [M ] resulted in characteristic fragment
ions with relative high intensity, in some cases as the base peak.
These ions are good hints to discriminate between large (R ≥ 4) and
small alkyl (R ≤ 3) group on 3. Details of these fragmentations will
be discussed with the chemicals in the following section.
chlorine and alkene from M+• resulted in a fragment ion at m/z
With these encouraging results, attention was focused on the
ꢀ
spectra of S,S -dialkyl methylphosphonodithioites 4 and S-alkyl
ꢀ
ꢀ
S -alkyl methylphosphonodithioites 5. Major EI fragment ions
of 4 and 5, as well as their retention indices (RI), are given in
Tables 2 and 3. The plausible fragmentation routes for them are
illustrated in Fig. 3.
EI–MS spectra of structural isomers of 4, bearing n-alkyl and
sec-alkyl on sulfur atom, show a great deal of similarity, as shown
in Fig. 4. As a result, misidentification may occur. Retention index
Scheme 3. Three possible structures of [C].
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Fig. 4. Representative EI–MS mass spectra of 4.
is a very good hint to discriminate between them. As expected, RI
of compounds containing sec-alkyl groups were less than those of
compounds containing n-alkyl groups (Table 2).
As mentioned above, in the EI spectra of 3, bearing
large alkyl (R ≥ 4), elimination of methyl phosphinchloride and
chloromethylphosphanyl radical gave rise to two distinctive frag-
ment ions, which can be used for the identification of alkyl moiety
on such chemicals. In case of R = n-pentyl or n-hexyl, these ions
appeared in m/z 102 and 103, respectively (Fig. 5).
Ion [A] is formed via cleavage of P CH3 bond from M+ , which
is observed in all the spectra of 4 and 5. Support for this route
is provided by the analysis of mass spectra of deuterated analogs
•
(
Tables 2 and 3). It should be mentioned that such a fragmentation
At the first, it can be considered that the proposed mecha-
nism for the formation of ions with m/z 102 in MS ion source for
S-n-pentyl methylphosphonochloridothioite (Fig. 5) and S,S -di-n-
pentyl methylphosphonodithioite (Fig. 6) is a concerted 1,3 C-P
hydrogen migration process (Scheme 4).
route is not observed in the spectra of S-alkyl methylphospho-
ꢀ
nochloridothioites 3, except chemicals bearing ethyl group on
sulfur. Cleavage of P CH3 bond from M+ in all EI–MS spectra of
•
4
and 5 should be dictated by symbiotic effect [18]. Expulsion of a
+•
methyl radical from M of 4 and 5 increases the symbiotic effect
of sulfur atoms in the ion [A]. Elimination of alkyl on sulfur as
According to the proposed mechanisms, the intensity ratio of
these ions should be the same in EI–MS spectra of both chemicals.
Intensity of ion at m/z 102 is higher than for the ion at m/z 103
in EI–MS of S-n-pentyl methylphosphonochloridothioite (Fig. 5).
+
•
alkyl radical or as an alkene molecule from M through 1,3 C-S
hydrogen shift gave fragments [B] and [C] with relative moderate
abundance, respectively. Fragment ion [D] can be generated pre-
sumably from the ion [A] by expulsion of an alkene or from M+• by
step-wise cleavage of CH3 P bond and elimination of alkyl as an
alkene. Deuterium labeling analysis confirmed this fragmentation
pathway. EI–MS spectra of 4 and 5 showed a strong ion at m/z 111
as [E], resulting with loss of both alkyl groups on sulfur atoms as
alkyl radical and alkene molecule. It should be noted that the ion
ꢀ
Surprisingly the intensity ratio of them in EI–MS spectra of S,S -di-
n-pentyl methylphosphonodithioite (Fig. 6) is vice versa. This may
suggest step-wise mechanisms for the formation of ion at m/z 102,
not concerted process.
As shown in Scheme 5, direct cleavage P SR bond initiated from
chlorine atom results in a radical-cation complex. Subsequently,
hydrogen radical transfer from cation to the radical gave rise to
[
E] is the base peak in chemicals 4, bearing R ≤ 4 on sulfur atoms.
form fragment ion at m/z 102.
•
When the S-alkyl chain length increases, the [E] signal decreases
in intensity. Formation of ion [F] (M -2(R-H)) by the loss of two
In chloromethylphosphanyl radical (CH PCl ), attachment of
3
+•
chlorine to phosphorous atom increases its affinity for the abstrac-
+
•
•
alkene molecules from M and hydrogen rearrangements was also
observed in EI–MS spectra of all chemicals 4. The base peak in EI–MS
spectra of chemicals bearing R ≥ 5 (Table 2, entry 10, 11, and 12) is
a diagnostic fragment at m/z 103, which will be discussed in the
following section.
tion of H . This conclusion is based on the hard and soft acids
and bases (HSAB) concept [18]. Therefore, the relative intensity
of the ion at m/z 102 is higher than the ion at m/z 103 in EI–MS
spectra of S-n-pentyl methylphosphonochloridothioite, while
in S-ethyl methylphosphanyl radical (CH PSEt ), attachment of
•
3
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7
Fig. 5. EI–MS spectrum of S-n-pentyl methylphosphonochloridothioite.
ꢀ
Fig. 6. EI–MS spectrum of S,S -di-n-pentyl methylphosphonodithioite.
S
X
S
X
S
X
H
direct cleavage P-S
1,3 C-P H migration
P
P
P
+
+
H
CH3
H
CH3
H
CH
3
m/ z 102
m/ z 103
,2 C-S H migration
3
4
, X = Cl
, X = SR
1
HS
Scheme 4. Primary proposed mechanism for the formation of ions at m/z 102 and 103 in EI–MS of 3 and 4.
sulfur to phosphorous atom causes a decrease in its affinity for
Some studied chemicals, 4 and 5, are isomeric pairs. The isomer-
ism among them is exclusively due to the size and structure of alkyl
substitutions attached to sulfur atoms. Fig. 7 shows representative
EI–MS mass spectra of an isomeric pair of 4 and 5. Overall spectra
of this pair look similar. The notable difference between the mass
spectra of them is the ratio of the fragment ion [E] to [F]. The ion [E]
is dominant in compounds bearing two small alkyl groups (R ≤ 3),
•
the abstraction of H ; thus, the relative intensity of the ion at m/z
ꢀ
1
03 is higher than the ion at m/z 102 in EI–MS of S,S -di-n-pentyl
methylphosphonodithioite. Energy calculations also confirmed
this observation. It shows that the formation energies of methyl
phosphinchloride and S-ethyl methylphosphonodithioite are 408
and 387 kcal/mol, respectively (Scheme 6).
S
X
S
X
HS
X
H
Hydrogen transfer
direct cleavage P-S
P
P
P
+
+
H
CH
3
CH
3
H
CH
3
3
, X = Cl
4
, X = SR
m/ z 103, base peak in 4
m/ z 102, base peak in 3
radical-cation complex
Scheme 5. Step-wise mechanism for the formation of ion at m/z 102 in EI–MS spectra of 3 and 4.
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H. Saeidian et al. / International Journal of Mass Spectrometry xxx (2015) xxx–xxx
Fig. 7. Representative EI–MS mass spectra of an isomeric pair of 4 and 5.
enriching OCAD, which may be used in OPCW verification activities,
Cl
P
Cl
H
P
on/off site analysis, and to improve MS interpretation knowledge.
Fragmentation processes were mostly dominated by hydrogen
rearrangement, alkene, and thiol elimination. Energy calculations
of fragment ions revealed their relative probability of formation
during ionization.
+
H
-
408 kcal/mol
CH3
CH3
chloro methylphosphanyl radical
EtS
H
EtS
P
P
-
387 kcal/mol
+
H
Appendix A. Supplementary data
CH3
s-ethyl methylphosphanyl radical
CH
3
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ijms.2015.12.004.
Scheme 6. Formation energies of methylphosphinchloride and S-ethyl
methylphosphonodithioite.
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