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

Article abstract of DOI:10.1007/s13361-016-1430-0

A new class of compounds, mono- and bis-haloethylphosphonates (HAPs and bisHAPs, respectively), listed in Schedule 2.B.04 of the Chemical Weapons Convention (CWC), has been synthesized and studied by GC-MS with two aims. First, to improve the identification of this type of chemicals by the Organization for the Prohibition of Chemical Weapons, (OPCW). Second, to study the synergistic effect of halogen and silicon atoms in molecules undergoing mass spectrometry. Fragmentation patterns of trimethylsilyl derivatives of HAPs were found to depend on the nature of the halogen atom; this was in agreement with DFT-calculations. The data suggest that a novel intramolecular halogen transfer takes place during the fragmentation process. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s13361-016-1430-0

B American Society for Mass Spectrometry, 2016
J. Am. Soc. Mass Spectrom. (2016)
DOI: 10.1007/s13361-016-1430-0
RESEARCH ARTICLE
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
Nerea Picazas-Márquez,1 María Sierra,1 Clara Nova,1 Juan Manuel Moreno,2
Nuria Aboitiz,1 Gema de Rivas,2 Miguel A. Sierra,3 Roberto Martínez-Álvarez,3
Esther Gómez-Caballero2
1Ingeniería de Sistemas para la Defensa de España (ISDEFE), Beatriz de Bobadilla 3, E-28040, Madrid, Spain
2Laboratorio de Verificación de Armas Químicas (LAVEMA), Área de Defensa Química, Subdirección General de
Sistemas Terrestres, INTA, Campus La Marañosa, San Martín de la Vega, E-28330, Madrid, Spain
3Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Complutense, E-28040, Madrid, Spain
Abstract. A new class of compounds, mono- and bis-haloethylphosphonates (HAPs
and bisHAPs, respectively), listed in Schedule 2.B.04 of the Chemical Weapons
Convention (CWC), has been synthesized and studied by GC-MS with two aims.
First, to improve the identification of this type of chemicals by the Organization for the
Prohibition of Chemical Weapons, (OPCW). Second, to study the synergistic effect of
halogen and silicon atoms in molecules undergoing mass spectrometry. Fragmenta-
tion patterns of trimethylsilyl derivatives of HAPs were found to depend on the nature
of the halogen atom; this was in agreement with DFT-calculations. The data suggest
that a novel intramolecular halogen transfer takes place during the fragmentation
process.
Cl
No
No
O
P
O
O
Br
Me
Me Si
I
3
Yes!!!
Halogen
Party
Dance
O
Invitation
O I
Si Me
P
Me
Me
Keywords: Iodine transfer, Haloethylphosphonates, Chemical weapons convention
Received: 10 February 2016/Revised: 19 May 2016/Accepted: 24 May 2016
off-site analysis [3]. The chemicals subject to control by the
Introduction
OPCW are listed in an Annex of the CWC under various
schedules relating to military and nonmilitary purposes, chem-
ical nature, etc. To carry out the mandatory CWAs verifica-
tions, the OPCW maintains an analytical database, the Central
Analytical Database (OCAD), which is a collection of gas
chromatography retention indexes (GC(RI)), infrared (IR),
mass spectrometry (MS), and nuclear magnetic resonance
(NMR) spectra for scheduled chemicals and related com-
pounds [4]. The primary on-site analytical tool is gas
chromatography/mass spectrometry (GC/MS). Therefore,
GC(RI) and MS data in the OCAD are the primary analytical
references [5]. Because these efforts are of critical international
importance, a large number of scientific articles regarding GC/
MS analysis of CWAs and related compounds has been report-
ed [6–26].
ecent use of chemical warfare agents (CWAs) during the
Syrian conflict has caused international apprehension [1];
R
in 1997, the CWC was created to protect the world from any
CWA attack; it prohibits the development, production, acqui-
sition, stockpiling, retention, transfer, or use of chemical
weapons [2]. The OPCW, the compliance body for CWC,
holds inspections that may include sampling and on-site or
Dedicated to Professor Michael Hanack (University of Tübingen, Germany) on
the occasion of his 85th birthday.
Electronic supplementary material The online version of this article (doi:10.
1007/s13361-016-1430-0) contains supplementary material, which is available
to authorized users.
The compounds of the present study belong to Schedule
2.B.04, which includes Ball chemicals, except for those listed in
Correspondence to: Roberto Martínez–Álvarez; e-mail: rma@quim.ucm.es

N. Picazas-Márquez et al.: Haloethylphosphonates and Intramolecular Halogen Transfer
O
P
X
O
P
O
P
X
X
HO
Experimental
General
O
OH
O
+
R
R
R
O
OH
OH
DCC/DMAP
60 oC
X
All the chemicals required for the synthesis of HAPS and
bisHAPs as well as the solvents and derivatizing agent N,O-
bis(trimethylsilyl)trifluoroacetamide (BSTFA) are commer-
cially available and were used without further purification.
bisHAPs (13-24)
APA
HAPs
BSTFA CH2Cl2
R = Me, Et, Pr, iPr
X = Cl, Br, I
O
X
Synthesis of bisHAPs and HAPs and Derivatization
with BSTFA (Scheme 1)
P
O
R
OSiMe3
1-12
N,N-dicyclohexylcarbodiimide (DCC, 0.15 mmol) and 4-
dimethylaminopyridine (DMAP, 0.04 mmol) were added to a
solution of the corresponding alkylphosphonic acid (APA,
0.1 mmol) in dichloromethane (1 mL) at room temperature.
The mixture was stirred at 60 °C for 1 h. Immediately follow-
ing, the corresponding haloalcohol (0.44 mmol) was poured
into the reaction and stirred at 60 °C for 3 h. Stock solutions
were prepared by dilution to the desired concentration with
dichloromethane and by derivatization with 200 μL of BSTFA
at 60 °C for 30 min in 2 mL sealed glass vials when necessary.
The corresponding bisHAPs and silylated HAPs were analyzed
by GC/MS.
Scheme 1. Synthesis of HAPs, bisHAPs, and TMS derivatives
investigated
Schedule 1, containing a phosphorus atom to which is bond-
ed one methyl, ethyl, or propyl (normal or iso) group but no
additional carbon atoms^ [2]. Since the degradation of
Scheduled 1 chemicals may lead to the formation of this
kind of organophosphorous compounds, some of them are
considered environmental markers of nerve agents [19, 24,
26]. Schedule 2.B.04 is open to many compounds. There-
fore, an understanding of the different classes of compounds
in 2.B.04 is of paramount importance. In this study, we
report the EI-MS data for new bis-haloethylphosphonates
(bisHAPs) and trimethylsilyl derivatives of mono-
haloethylphosphonic acids (HAPs). Through a combination
of experimental and computational methods, we have dis-
covered new, unprecedented fragmentation patterns of some
of these compounds. Specifically, an iodine transfer may be
of relevance in the spectral interpretation of compounds in
the OCAD and related data bases.
GC/MS(EI) Analysis
The GC/MS analyses were conducted in electron ionization
(EI) mode (70 eV) using an Agilent 6890 gas chromatograph,
equipped with a 5973 MSD model (Agilent Technologies, Palo
Alto, CA, USA). An HP5 column (5% phenyl 95% methyl-
polysiloxane; 30 m length, 0.25 mm i.d., and 0.25 mm film
thickness) was used at a temperature program of 40 °C (1 min),
Table 1. Significant Peaks 25–29 (m/z, Relative Peak Intensities) in the Mass Spectra of Monohalogenated TMS Derivatives 1–12
Compound
R
X
25
26
27
28
29
1
Me
Me
Me
Et
Cl
Br
I
215 (30)
259 (20)
195(55)
195 (65)
153 (100)
153 (100)
151 (40)
151 (40)
C6H16ClPO3Si
2
C6H16BrPO3Si
3
C6H16lPO3Si
4
C7H18ClPO3Si
5
C7H18BrPO3Si
6
C7H18IPO3Si
7
C8H20ClPO3Si
8
C8H20BrPO3Si
9
C8H20IPO3Si
10
C8H20ClPO3Si
11
C8H20BrPO3Si
12
C8H20IPO3Si
307 (<10)
306.9439
229 (30)
195 (75)
195.0446
209 (72)
279 (100)
278.8776
153 (65)
152.9995
167 (100)
151 (50)
151.0257
165 (38)
Cl
Br
I
Et
275 (20)
321 (<10)
243 (45)
287 (30)
335 (<10)
243 (50)
287 (35)
335 (10)
209 (72)
167 (100)
165 (50)
Et
209 (80)
209.0660
223 (80)
293 (100)
292.8932
167 (60)
167.0181
181 (100)
165 (50)
165.0417
Pr
Cl
Br
I
Pr
223 (95)
181 (100)
181 (50)
181 (100)
181 (85)
179 (60)
Pr
223 (100)
223.0793
223 (100)
307 (98)
306.9146
179 (70)
179.0565
i-Pr
i-Pr
i-Pr
Cl
Br
I
223 (100)
179 (70)
223 (90)
223.9081
307 (100)
306.9513
181 (60)
181.0529
179 (80)
179.0773

N. Picazas-Márquez et al.: Haloethylphosphonates and Intramolecular Halogen Transfer
O
GC/MS plots as well as the retention indexes (RIs) of
O
R
P
the investigated compounds are included in the Supple-
mentary Material. HRMS spectra were recorded using a
TOF GCT Premier from Waters (Manchester, UK)
Micromass coupled with a gas chromatograph 7890A
from Agilent with continuous internal calibration, scan
time of 0.9 s, and inter-scan delay of 0.1 s, and are
included in the Supplementary Material.
X
OSiMe3
1-12
X = Cl, Br, I
- X
CH3
O
R
O
P
O
R
O
P
X
X = I
OSiMe3
O
GC/MS(CI) Analysis
SiMe2
The molecular mass of the compounds subject to this
study was confirmed by GC/MS analysis conducted in
chemical ionization (CI) mode using a Varian (Palo Alto,
CA, USA) 3400 gas chromatograph, equipped with a
Saturn 2000 ion trap. Chromatographic conditions were
identical to those described for above. The spectra were
acquired at a CI source temperature of 200 °C and
acetonitrile as reactant gas, with unit mass resolution,
scan range m/z 80–500 and a scan cycle of 2.5 scans/s.
25
26
O
P
R
O
O
X
X
SiMe2
27
O
P
O
R
OH
R
P
O
OSiMe3
SiMe2
28
29
Scheme 2. Proposed fragmentation pattern for TMS deriva-
tives of (2-haloethyl)alkylphosphonates 1–12
Computational Details
All calculations were performed at the DFT level using
the uB3LYP functional [27, 28] as implemented in
Gaussian 09 [29]. Cl, Br, and I atoms were described
using the lanl2dz pseudopotential [30]. The 6-31G**
basis set was used for the H, C, N, and O atoms [31,
32]. All structures of the reactants, intermediates, transi-
tion states, and products were fully optimized in vacuo
[31]. Transition states were identified by having one
imaginary frequency in the Hessian matrix. It was
then raised at 10 °C/min to 280 °C, where it was held
for 5 min. Helium was used as the carrier gas at a
constant flow of 1 mL/min. The samples were injected
in splitless mode at an injection temperature of 250 °C
and 1 μL volume. The spectra were acquired at an EI
source temperature of 230 °C and a quadrupole analyzer
temperature of 150 °C, with unit mass resolution, scan
range m/z 40–500 and a scan cycle of 3.15 scans/s. The
Figure 1. EI Mass spectrum of 2-iodoethyl trimethylsilyl methylphosphonate 3

N. Picazas-Márquez et al.: Haloethylphosphonates and Intramolecular Halogen Transfer
Figure 2. EI Mass spectrum of 2-chloroethyl trimethylsilyl methylphosphonate 1
confirmed that transition states connect with the corre-
sponding intermediates by means of application of the
eigenvector corresponding to the imaginary frequency
and subsequent optimization of the resulting structures.
All energies collected in the text are Gibbs energies at
298 K.
X
X
X = Cl -17.3
O
X = Cl 15,5
X = Br 19.8
X = I 10.7
O
O
P
X = Br -16,5
X = I -11.8
P
O
X
O
Me
+
CH3
O
O
Me
Me
P
Me
Me
Me
Si
Me3Si
Me
O
Si
O
I1
Me
X = Cl 0.0
X = Br 0.0
X = I 0.0
I2
TS1
X = Cl 26.0
X = Br 26.9
X = I 29.1
X
X = Cl 25.4
X = Br 28.1
X = I 31.6
X = Cl -25.4
X = Br -28.1
X = I -31.6
X
X
O
Me
O
Si
O
Me
Me
O
Si
P
O
Si
Me
P
Me
Me
O
P
O
O
Me
Me
Me
O
I3
TS3
TS2
X = Cl -21.8
X = Br -20.7
X = I -20.1
O
Me
Si
X = Cl -5.0
X = Br -10.7
X = I -16.2
O
X
X = Cl 68.8
X = Br 57.3
X = I 48.2
X
O
P
P
X
Me
Me
+ H2C=CH2
O
Si Me
O
O
Si
Me
Me
P
Me
Me
O
Me
O
X = I
27 (M-43)
TS4
I4
Scheme 3. Calculated reaction pathway for the fragmentation of I1. ΔG‡ values are given in kcal mol–1

N. Picazas-Márquez et al.: Haloethylphosphonates and Intramolecular Halogen Transfer
O
fragmentation in the mass spectrometry of these derivatives
[33]. This elimination is independent of the nature of the halogen
atom (chlorine or bromine) in the molecule. Variation of the
alkyl group attached to phosphorus atom produces no significant
effect in the general fragmentation of these TMS derivatives. The
loss of a methyl radical is followed by the elimination of a vinyl
halide molecule (CH2=CHX) to form the base peak of the spectra
(28), except when the halogen is iodine (compounds 3, 6, 9, and
12). The formation of fragments such as 26 for chlorine and
bromine derivatives can be explained as a result of a direct
elimination of a halogen radical from the undetected molecular
ion (Scheme 2). On the other hand, iodine derivatives behave
differently; the loss of a methyl group produces fragments of
very low abundance, which subsequently undergo an ethylene
molecule elimination leading to fragments such as 27. Accurate
mass measurements confirm these two consecutive eliminations.
Figure 1 (compound 3) is representative of the behavior of these
iodinated TMS derivatives, whereas Figure 2 shows the spectra
of a chlorine homologue (1) for comparison.
To explore the remarkable differences between iodides (3,
6, 9, and 12) and their chloro- and bromo-substituted conge-
ners, DFT calculations were carried out for compounds 1, 2,
and 3 (R = Me, X = Cl, Br, I) (see computational procedures
and Scheme 3). Regardless of the halogen, the loss of one Me-
group attached to the silicon easily occurs from the initially
formed radical cation I1. This process is assisted by the P=O
bond forming the cyclic intermediates I2 through TS1. This
step is more difficult for bromide 2 (ΔG‡ = 19.8 kcal mol–1) and
for chloride 1 (ΔG‡ = 15.5 kcal mo–1) being easiest for iodide 3
(ΔG‡ = 10.7 kcal mol–1). Nevertheless, the differences encoun-
tered between the three halogens have to be found lately in the
reaction mechanism leading to 27, since the evolution of I2 to
28 or 29 takes place irrespective of the halogen. Subsequently,
I2 evolves to I3 through TS2, which involves the attack of the
halogen (Cl, q = –0.03; Br, q = 0.01; I, q = 0.12) to the electron
deficient silicon center (when X = Cl, q=1.58; X = Br, q = 1.58;
X = I, q = 1.58). In this step, the oxygen tethered to the silicon
in I2 is displaced, forming the cyclic intermediate I3. Now, the
O
I
Me
P
OSiMe3
30 (M =336)
- I
CH3
O
P
O
P
Me
O
Me
O
I
OSiMe3
O
SiMe2
m/z 209 (38%)
m/z 321 (10%)
I
O
P
O
Me
O
Me
OH
P
I
SiMe2
O
SiMe2
m/z 279 (<10%)
m/z 153 (100%)
Scheme 4. Proposed fragmentation pattern for 3-iodopropyl
trimethylsilyl methylphosphonate 30
Results and Discussion
Unmodified mono-haloethylphosphonates (HAPs) cannot be
analyzed by GC since their high polarity and nonvolatile nature
preclude their submission without degradation. To overcome
this problem, these compounds were treated with BSTFA to
form the corresponding monosilylated derivatives 1–12. Ta-
ble 1 compiles the most significant ions observed in the EI
mass spectra of the prepared TMS derivatives while the corre-
sponding mass spectra can be found in the Supplementary
Material (SF1–16). Peaks for the molecular ions were not
observed. The molecular mass of 1–12 was confirmed, how-
ever, by GC/MS(CI) (Supplementary Material SF17–19).
Data in Table 1 show that the first fragmentation corresponds
to a methyl radical elimination, probably from the trimethylsilyl
group, to form the corresponding fragments 25. The loss of a
methyl radical bonded to the silicon atom is a well known
Table 2. Significant Peaks 31–36 (m/z, Relative Peak Intensities) in the Mass Spectra of Chloride and Bromide bisHAPs
Compound
R
X
31
32
33
34
35
36
13
Me
Et
Cl
Cl
Cl
Cl
Br
Br
Br
Br
185 (100)
199 (100)
213 (100)
213 (100)
229 (81)
243 (92)
257 (59)
257 (100)
159 (32)
173 (11)
-
97 (34)
63 (42)
141 (74)
155 (83)
169 (76)
169 (73)
185 (48)
199 (64)
213 (32)
213 (62)
79 (62)
93 (30)
107 (<2)
107 (<2)
79 (74)
93 (44)
107 (25)
107 (<2)
C5H11Cl2PO3
16
C6H13Cl2PO3
19
C7H15Cl2PO3
22
C7H15Cl2PO3
14
C5H11Br2PO3
17
C6H13Br2PO3
20
111 (29)
125 (23)
125 (15)
97 (41)
63 (26)
Pr
63 (40)
iPr
Me
Et
187 (19)
203 (21)
217 (24)
229 (25)
231 (18)
63 (32)
107 (100)
107 (100)
107 (100)
107 (100)
111 (34)
125 (18)
125 (20)
Pr
C6H13Br2PO3
23
iPr
C6H13Br2PO3

N. Picazas-Márquez et al.: Haloethylphosphonates and Intramolecular Halogen Transfer
Table 3. Significant Peaks 37–41 (m/z, Relative Peak Intensities) in the Mass
Spectra of Iodine bisHAPs
with 27 (M-43) was found by attacking the silicon atom of I1
with the oxygen tethering the halogenoethenyl chain. This
pathway is similar to the one depicted in Scheme 3. Although
this pathway is also suitable to explain the different behavior of
iodine compared with chlorine or bromine, the energies in-
volved in the key step are >100 kcal mol–1. Therefore, it seems
less probable than the proposed mechanism pathway in
Scheme 3. It is remarkable that although some heteroatom
transfers have been reported as examples of the hetero
McLafferty rearrangement [35–39], no data for similar iodine
consecutive transfers have been described in the literature.
The proposed mechanism for the formation of fragment 27
(Scheme 2) is supported by the mass spectra of 3-iodopropyl
trimethylsilyl methylphosphonate 30 (M = 336, SF20) which
was prepared (see Experimental) using 3-iodopropanol as the
corresponding alcohol. The spectrum reveals a base peak at m/z
153, the proposed formation of which begins with Me-cleav-
age. Formation of an oxetane ring, however, is disfavored since
its transition state homologous to TS2 in Scheme 3 would have
an eight-membered ring. Instead, the elimination of methyl
radical is followed by the loss of a propenyliodide molecule
(168 Da) to form the main fragment at m/z 153 (Scheme 4).
Nevertheless, the fragment at m/z 279, generated as a conse-
quence of consecutive eliminations of methyl radical and pro-
pylene molecule (42 Da), involving a iodine atom transfer
similar to the calculated in Scheme 2, is formed albeit in low
abundance (<10%). All the attempts to compute a reaction
pathway connecting I2 (Scheme 3) to the corresponding I3
for the homologous 30 were fruitless.
Compound
R
37
38
39
40
41
15
Me 250 (38) 97 (18)
249.9190
123 (100) 79 (22)
123.0165
155 (84)
154.9340
155 (75)
154.9340
C5H11I2PO3
18
C6H13I2PO3
21
C7H15I2PO3
24
C7H15I2PO3
Et
264 (28) 111 (24) 137 (100) 93 (16)
263.9308 137.0324
Pr
278 (22) 125 (25) 151 (100) 107 (13) 155 (70)
277.9475
iPr 278 (26) 125 (25) 151 (100) 107 (9)
277.9755 151.0617
155 (65)
154.9444
energies for this displacement are very similar for the three
halogens with the iodine being slightly disfavored. Cyclic
cation I3 evolves to I4 by an intramolecular attack of the
oxygen tethered to the halogenoethenyl chain. The energies
involved are again similar for the three halogens with iodine
being slightly disfavored compared with chlorine or bromine.
The final step of the mechanism consists of the extrusion of an
ethylene molecule from I3 to give the observed 27 (M-43).
This process is analogous to one reported for the fragmentation
of halogen-substituted amines via intramolecular halogen
transfer [34]. This rate-determining step is clearly favored for
the more nucleophilic iodine (ΔG‡ = 48.2 kcal mol–1) com-
pared with chlorine (ΔG‡ = 68.8 kcal mol-1) or bromine (ΔG‡ =
57.3 kcal mol–1). These energies are congruent with the exper-
imentally observed behavior of compounds 1–3.
To discard other possible fragmentation pathways, we have
computed the direct halogen transfer to the P=O bond in I1 as
an alternative hetero McLafferty type six-membered rearrange-
ment to explain both the Me and ethylene eliminations, togeth-
er with the reactivity differences between halogens. So far, we
have been unable to find a reaction pathway connecting I1 with
the product resulting from the transfer of the iodine atom to the
P=O bond. However, a high energy pathway connecting I1
Finally, a comparative study was made with the correspond-
ing ethyl trimethylsilyl alkylphosphonate acids [4, 40] (SF21–
24). Similar to the results for compounds 1–12, the elimination
of the methyl radical (M-15) that forms product-ions as 25
(Scheme 2, X = H) followed by the loss of an ethylene mole-
cule leads to the base peaks with structure identical to 28.
O
O
R
P
X
O
X
bisHAPs
X = Cl, Br
X
X
O
P
O
P
O
R
OH2
R
O
R
OH2
X
P
O
O
OH
X
X
X
34
31
32
33
H2O
O
P
O
P
R
R
O
OH
O
X
X
35
36
Scheme 5. Proposed fragmentation pattern for bis(2-chloroethyl) and bis(2-bromoethyl) alkylphosphonates

N. Picazas-Márquez et al.: Haloethylphosphonates and Intramolecular Halogen Transfer
Figure 3. EI Mass spectrum of bis(2-chloroethyl)methylphosphonate 13
The EI mass spectra of all bisHAPs studied (13–24) lacked the
odd-electron molecular ions (Tables 2 and 3, SF 25–40). The
molecular masses of these compounds were confirmed by GC/
MS(CI) (SF 41–43). Furthermore, fragments from the cleavage
of the P–C bond were also absent from the spectra, whereas this
dissociation was detected in the mass spectra of α-amino
phosphonates [41] and spiro alkylphosphonates [42]. Again,
the nature of the halogen atom (X) plays a crucial role in the
fragmentation pathway of compounds 13–24.
Thus, the homolytic cleavage of the C-halogen bond with
the subsequent loss of the corresponding halogen radical is the
main fragmentation for chlorinated bisHAPs to form the ion
fragments 31 (Table 2 and Scheme 5). Figure 3 shows the EI
mass spectrum of bis(2-chloroethyl)methylphosphonate 13 (M
Figure 4. EI Mass spectrum of bis(2-bromoethyl)methylphosphonate 14

N. Picazas-Márquez et al.: Haloethylphosphonates and Intramolecular Halogen Transfer
O
P
Fragmentations involving a double hydrogen atom transfer to
the P=O bond (McLafferty + 1 rearrangement) can also be
O
R
I
O
observed for chlorine and bromine bisHAPs. Thus, the elimi-
I
nation of a halogen vinylidene radical (XCH=CH●) leads to the
formation of fragments type 32, which evolve either by loss of
a water molecule, forming 35, or by elimination of a
vinylhalogenide molecule leading to 33. The subsequent elim-
ination of a vinyl halide molecule (CH2=CHX) from 35 gen-
erates the fragment ion 36 (Scheme 5).
bisHAPs
X = I
I
O
P
O
R
OH
R
OH2
To better understand the mass spectrometry of these halo-
genated compounds, a comparative study with the correspond-
ing diethyl alkylphosphonates (dEAPs) was carried out [4, 40,
43]. Similar to the observed fragmentations of bisHAPs,
diethyl methylphosphonate and diethyl ethylphosphonate (SF
44–45) undergo a McLafferty type-rearrangement with a dou-
ble hydrogen atom transfer to the P=O bond with loss of a
halogen vinylidene radical (XCH=CH●) forming ions at m/z
125 and 139, respectively [4, 40, 43]. Two subsequent elimi-
nations of ethylene and water molecules, respectively, lead to
the formation of the most significant peaks of the spectra.
Differences were found, however, between the fragmenta-
tions of bisHAP chlorides, bromides, and iodides (Table 3 and
Scheme 6). The reason could be attributed to the C-I bond’s
lower dissociation energy compared with those for the C–Cl and
C–Br bonds [44, 45]; this would lead to a different fragmentation
mechanism. The mass spectra of the iodides lack M+ and [M –
I]+ ions. Instead, a molecule of vinyl iodide is promptly elimi-
nated, affording fragments such as 37, which evolve either by
undergoing a McLafferty rearrangement with double hydrogen
transfer to form 38, or by loss of an iodine radical to
form 39. Additionally, a direct elimination of
I
P
O
OH
I
I
41
m/z 155
38
37
H2O
I
O
P
O
P
R
OH
R
OH
O
40
39
Scheme 6. Proposed fragmentation pattern for bis(2-
iodoethyl) alkylphosphonates
= 220) with the base peak at m/z 185 (fragment type 31, R =
Me, X = Cl). Although brominated bisHAPs also eliminate
bromine radical to form an ion at m/z 229, this ion is not the
base peak. The main peak for the brominated compounds
corresponds to the three membered cyclic ion [C2H4Br]+ (34,
X = Br, m/z 107). Figure 4 shows the EI mass spectrum of
bis(2-bromoethyl)methylphosphonate 14 (M = 308).
Figure 5. EI Mass spectrum of bis(2-iodoethyl)methylphosphonate 15

N. Picazas-Márquez et al.: Haloethylphosphonates and Intramolecular Halogen Transfer
Acknowledgments
iodoethylene radical (155 Da) produces fragments in low
abundance. The EI mass spectrum of bis(2-
iodoethyl)methylphosphonate 15 (Figure 5) reveals peaks
at m/z 155 [C2H4I]+ and the product of elimination of
155 Da (M-155, m/z 249). The presence of both frag-
ments indicates that a competition process to retain the
charge between these fragments is taking place. The
fragment at m/z 155 (41) shows a higher abundance
because it can retain the charge more easily than the
Financial support from the Spanish MINECO (CTQ2013-
46459-C2-1P; and CTQ2014-51912-REDC) is acknowledged.
The authors are very grateful for the help of Professor John
Almy (CSU, Stanislaus, CA, USA) for fruitful discussions and
careful editing of the manuscript.
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●
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