Gas chromatography-mass spectrometric studies of O-alkyl 0-2-(N,N-dialkylamino) ethyl alkylphosphonites(phosphonates) for Chemical Weapons Convention verification

Article abstract of DOI:10.1255/ejms.1234

The electron ionization (EI) mass spectra of a series of O-alkyl O-2-(NN-dialkylamino)ethyl alkylphosphonites(phosphonates) which are precursors of nerve agents were studied for Chemical Weapons Convention (CWC) verification General EI fragmentation pathways were constructed and discussed Proposed fragment structures were confirmed through analyzing fragment ions of deuterated analogs and density functional theory (DFT) calculations The observed fragment ions are due to different fragmentation pathways such as hydrogen and McLafferty+1 rearrangements alkene amine and alkoxy elimination by α-or β-cleavage process Fragment ions distinctly allow unequivocal identification of the interested compounds including those of isomeric compounds The presence and abundance of fragment ions were found to depend on the size and structure of the alkyl group attached to nitrogen phosphorus and oxygen atoms IM Publications LLP 2013.

Full text of DOI:10.1255/ejms.1234

H. Saeidian et al., Eur. J. Mass Spectrom. 19, 361–375 (2013)
361
Received: 10 July 2013
n
Accepted: 22 October 2013 n Publication: 28 October 2013
EUROPEAN
JOURNAL
OF
MASS
SPECTROMETRY
Gas chromatography-mass spectrometric
studies of O-alkyl O-2-(N,N-dialkylamino)
ethyl alkylphosphonites(phosphonates) for
Chemical Weapons Convention verification
Hamid Saeidian,a,* Mehran Babri,b* Atefeh Ramezani,a Davood Ashrafi,b Mansour Sarabadanib and
Mohammad Taghi Naserib
aDepartment of Science, Payame Noor University (PNU), PO Box 19395-4697, Tehran, Iran. E-mail: h_porkaleh@yahoo.com
bDefense Chemical Research Lab (DCRL), PO Box 31585-1461, Karaj, Iran
The electron ionization (EI) mass spectra of a series of O-alkyl O-2-(N,N-dialkylamino)ethyl alkylphosphonites(phosphonates), which
are precursors of nerve agents, were studied for Chemical Weapons Convention (CWC) verification. General EI fragmentation pathways
were constructed and discussed. Proposed fragment structures were confirmed through analyzing fragment ions of deuterated ana-
logs and density functional theory (DFT) calculations. The observed fragment ions are due to different fragmentation pathways such
as hydrogen and McLafferty+1 rearrangements, alkene, amine and alkoxy elimination by a- or b-cleavage process. Fragment ions
distinctly allow unequivocal identification of the interested compounds including those of isomeric compounds. The presence and abun-
dance of fragment ions were found to depend on the size and structure of the alkyl group attached to nitrogen, phosphorus and oxygen
atoms.
Keywords: mass spectrometry, Chemical Weapons Convention, alkylphosphonites(phosphonates), DFT calculations,
McLafferty+1 rearrangement
Introduction
An ongoing area of research in our laboratory in recent years
and four main precursors for the preparation of nerve agents
has been the utilization of microsynthesis and mass spec- (Part B). Schedule 2 lists three toxic chemicals not included
tral studies of organophosphorus compounds for verification
in Schedule 1 and the degradation products and precursors
of these toxic chemicals as well as of those of Schedule 1.
purposes under the Chemical Weapons Convention (CWC).1–3
This convention, which prohibits development, produc- Schedule 3 lists four toxic chemicals and some precursors
tion, stockpiling and use of chemical weapons, was avail- not listed in the other schedules. The state parties established
able for signature on January 13, 1993 and came into force
on April 29, 1997. For CWC implementation, toxic chemicals, (OPCW) to achieve the object and purpose of CWC.4 In order
precursors and most related chemicals are listed in three to detect and identify CWC-related chemicals in different
the Organization for the Prohibition of Chemical Weapons
distinct CWC schedules contained in the annex on chemicals. matrices, OPCW maintains a network of designated laborato-
Schedule 1 includes chemicals which were used in a chem- ries. Only designated laboratories are authorized to undertake
ical weapon such as mustard gas or nerve agents (Part A)
the task of off-site analysis in verification activities. Analytical
ISSN: 1469-0667
doi: 10.1255/ejms.1234
© IM Publications LLP 2013
All rights reserved

362
GC/MS Studies O-2-(N,N-Dialkylamino)ethyl Alkylphosphonites(phosphonates)
performance of designated laboratories and laboratories
seeking designation is regularly evaluated by OPCW through
official proficiency tests.5 For unequivocal identification of
the CWC-related chemicals in real samples or proficiency
tests, the availability of mass spectra and interpretation skills
are essential requirements. The OPCW Central Analytical
Database (OCAD) is the major source for CWC-related refer-
ence mass spectra.6 This database has been developed by
laboratory contributions of the member states. It is impossible
to have a complete collection of mass spectroscopic data for
all CWC-related chemicals, in part due to the extreme toxicity
with possible fragmentation routes. Structures of fragments
were confirmed using analysis of deuterated analogs.
Density functional theory (DFT) was used to reveal preferred
fragmentation pathways. This paper will make a substantial
contribution to OCAD.
Experimental
Reagents and chemicals
All chemicals required for microsynthesis of O-alkyl O-2-(N,N-
of these materials, which restrict research on such chemicals. dialkylamino)ethyl alkylphosphonites(phosphonates) were
In recent years, some research results have been reported
on microsynthesis and interpretation of mass spectra of
CWC-related chemicals.7–12
Among the scheduled chemicals, nerve agents constitute
the greatest worry, due to their highly toxic effects on humans
and facile and inexpensive synthesis. Well known chemicals
are tabun, sarin, soman and VX. Nerve agents inhibit the
enzyme acetylcholinesterase (AChE) which hydrolyzes and
purchasedfromSigma–Aldrich(StLouis, MO, USA), Fluka(Neu-
Ulm, Germany) and Merck (Darmstadt, Germany) and were
used as received. Alkyl dichlorophosphine, alkylphosphonic
dichloride were synthesized using the existing method.15,16
Isopropanol-d6 was prepared through reduction of acetone-d6
by sodium borohydride.17
GC/MS analyses
terminates the action of the neurotransmitter acetylcholine. The GC/MS analyses were performed using an Agilent 6890N
Inhibition of AChE results in overstimulation of cholinergic
nerves leading to respiratory paralysis.13,14 Therefore, fast
analysis and identification of these agents, their precursors
and degradation/reaction products (CWC-related chemicals)
are essential in selecting the most effective countermeasure
against them. O-alkyl O-2-(N,N-dialkylamino)ethyl
alkylphosphonites with general structure (I) are placed in CWC
as Schedule 1.B.10 (Figure 1). These chemicals are precursors
gas chromatograph equipped with a 5973 mass selective
detector, a HP-5MS capillary column (30m, 320µm i.d. and
0.25 µm film thickness) and helium as the carrier gas at a
constant flow of 1.8 mL min–1. The oven temperature was
set at 40°C for 3min and was then increased to 280°C with
a ramp of 10°Cmin–1 and held for 6min. The samples were
injected in splitless mode at an injection temperature of
250°C. The temperatures of the EI source and analyzer
of highly toxic nerve agents known as V-agents. For example, were kept at 230°C and 150°C, respectively. The ionization
2-ethyl O-2-(N,N-diisopropylamino)ethyl methylphosphonite energy was set at 70 eV. The scan range was m/z 40–500.
(QL) is used as a starting material for the synthesis of VX. Automated mass spectral deconvolution and identification
The OPCW Central Analytical Database (OCAD) has very poor
informationonthedataofalkylphosphonites. Atthistime, there
is only one spectrum for alkylphosphonite compound (QL). On
the other hand, oxidation of O-alkyl O-2-(N,N-dialkylamino)
ethyl alkylphosphonites gives O-alkyl O-2-(N,N-dialkylamino)
ethyl alkylphosphonates (II), which are also included in the
CWC Schedule 2.B.4. Although mass data of some derivatives
of II were entered in the OCAD, no detailed investigation on
the mass spectral fragmentation process of these chemicals
(I and II) and their isotopically-labeled derivatives are found in
the literature.
system (AMDIS) software was used to calculate the reten-
tion indices (RI) of the synthesized compounds. An alkane
mixture [octane (C8) to tetracosane (C24)] was used for reten-
tion indices calculations.
Computation details
All geometry optimizations and frequency calculations for all
species were performed by using the Gaussian 03 program.18
Density functional theory (DFT) calculations with the Becke
three parameters hybrid functional (DFT-B3LYP) were carried
out, with a 6-311 ++G (d, p) basis set for all atoms. Vibrational
frequencies were calculated at the same level to ensure that
each stationary point is a true minimum. The harmonic-
oscillator approximation was also used for the thermodynamic
Since verification activities, in general, rely on gas
chromatography-mass spectrometry (GC/MS), this paper is
devoted to electron ionization (EI) mass spectra of I and II
R3
N
R1
P
R3
R1
O
N
P
R3
O
OR2
R3
O
OR2
phosphonite (I)
phosphonate (II)
R1 = CH3, C2H5, R2 = CH3, C2H5, CD3, C2D5, i-C3HD6, R3 = CH3, C2H5, i-C3H7
Figure 1. General structure of O-alkyl O-2-(N,N-dialkylamino)ethyl alkylphosphonites(phosphonates).

H. Saeidian et al., Eur. J. Mass Spectrom. 19, 361–375 (2013)
363
partition functions. After geometry optimization and frequency
influencedbythealkylgrouponnitrogen.Whenalkylonnitrogen
calculations, zero-point energies (ZPEs) and thermal correc- (R3) becomes larger, the intensity of [A] decreases or vanishes.
tions were obtained at 298K.
In R3 = CH3 analogs, this ion abundance is the third largest
peak in the mass spectra. Ion [A] was clearly distinguishable
in the spectra of deuterated analogs. In addition, formation of
the ion [D] from [A] through a 1,3-hydrogen shift is an evidence
for α-cleavage of a P–C bond, which can be seen in the spectra
of deuterated analogs. It is interesting to note that ion [A]
could be related to three possible structures (Figure 3), in
which [A1] and [A2] are resonance forms. The free energy of
structure [A1], in the case of R2 =R3 =CH3 was calculated to be
112kJmol–1 and 23kJmol–1 less than that of structure [A2] and
[A3], respectively. This indicates a preference for the formation
General procedure for microsynthesis
of O-alkyl O-2-(N,N-dialkylamino)ethyl
alkylphosphonites I
A solution of alcohol (R2OH, 0.2mmol), 2-(N,N-dialkylamino)
ethanol (0.2 mmol) and triethylamine (0.4 mmol) in CH2Cl2
(200µL) was added to a solution of alkyl dichlorophosphine
(0.2 mmol) in dry dichloromethane (300µL), under nitrogen
atmosphere dropwise, while stirring. The reaction mixture was
stirred at ambient temperature for an hour. Any precipitate
was filtered off and the resulting solution of O-2-(N,N- of structure [A1]. The C−N or C−H bonding electrons in [A1] can
dialkylamino)ethyl alkylphosphonites I was analyzed using
GC/MS as required.
delocalize to stabilize the electron deficient oxygen atom. In
other words, the effect of bonding electrons of C−N or C−H on
stabilization of [A1] can be represented by hyperconjugation
*
(s®s , Figure 4).23 The implication of this resonance structure
General procedure for microsynthesis
of O-alkyl O-2-(N,N-dialkylamino)ethyl
alkylphosphonates II
is that some electron density is transferred from a C–N or C–H
*
bond (s, as HOMO) to the empty s orbital (as LUMO) of a C–O
Alcohol (R2OH, 0.2 mmol), 2-(N,N-dialkylamino)ethanol
(0.2mmol) and triethylamine (0.4mmol) in CH2Cl2 (200µL) was
added to a solution of alkylphosphonic dichloride (0.2mmol) in
bond. The C–O bond with the electron deficient oxygen atom is
better able to accept electron density.
Elimination of the 2-(N,N-dialkylamino)ethanol radical
dichloromethane (300µL) dropwise, while stirring. The reac- from molecular ion (M+•) by α-cleavage caused formation of
tion mixture was stirred at ambient temperature for an hour. ion [B]. Fragmentation of deuterated analogs also showed
Any precipitate was filtered off and the solution was analyzed
using GC/MS as required.
this ion. The intense ions [E], [F] and [G] were produced
from the 2-(N,N-dialkylamino)ethanol group. Presence of
CAUTION: These compounds are extremely toxic and, these fragments in the mass spectra is a good indication
therefore, should be handled only by a trained professional in
an efficient fume cupboard equipped with an active charcoal
filtration system.
of 2-(N,N-dialkylamino)ethanol in I. Fragment ion [C] could
be formed through the loss of an alkoxy radical from the
M+•. Ion [C] further fragmented to ion [H] by the migration
of one hydrogen to the P=O group. Elimination of alkoxy as
a radical and one alkyl group on nitrogen as the neutral
alkene gave rise to ion [I]. Fragment ion [J] is attributed to
the loss of N,N-dialkylethylamine as a radical via b-cleavage.
Its corresponding deuterated ion in the mass spectra of
deuterated analogs could support such a fragmentation
pathway. Leaving a neutral aldehyde and alkene from [J] gave
rise to ions [M] and [N], respectively. Direct elimination of the
N,N-dialkylamine moiety from M+• yielded ion [K]. The ions [L]/
[L¢] can be postulated to arise via hydrogen shift involving both
Results and discussion
EI-MS of O-alkyl O-2-(N,N-dialkylamino)ethyl
alkylphosphonites I
GC retention indices (RI) for contribution to the OCAD were
calculated using the Van Den Dool method.19 It is interesting
to note the effect of heavy isotopes on retention indices
of isotopically-labeled compounds. Deuterosubstitutions
can have an influence on the vaporization, diffusion, parti- oxygen atoms and a phosphorus atom (Figure 5). The radical
tion and lipophilicity of the analyte which are influencing
its interactions with the GC stationary phase.20 Retention
index depends on vapor pressure.21 For most unlabeled and
labeled compounds, inverse vapor pressure isotope effects
have generally been seen, pD >pH.22 In this study, the RI values
of labeled compounds are less than unlabeled compounds
(Table 1).
EI mass spectra of I showed that their fragmentation
follows a general pathway involving a- and b-cleavage and
amine, alkene and aldehydes elimination etc. Prominent EI
fragment ions of I are listed in Table 1 and their corresponding
structures are depicted in Figure 2.
cation can be produced by knocking out one non-bonding
electron either from phosphorus (route L), or from one of the
two oxygen atoms (route L¢). The proposed fragmentation
pathway (L) involves an initial hydrogen migration (1,4 C-P H
shift) to the phosphorus-bearing radical cation site, leading
to a distonic species. The second hydrogen is abstracted as
a hydride in a concerted manner, with simultaneous hydride
migration (1,3 C–O H– shift) and single bond cleavage involving
a four-membered cyclic state. The proposed fragmentation
pathway (L¢) also involves an initial hydrogen migration (1,5
C–O H shift) to the oxygen-bearing radical cation site, leading
to a distonic species followed by a 1,3 C–O H– shift to the other
oxygen atom through a four-membered transition state with
expulsion of a N,N-dialkylethenamine radical.
The most important fragment ion [A] is formed through
a-cleavage of P−C bond. The intensity of this special ion is

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GC/MS Studies O-2-(N,N-Dialkylamino)ethyl Alkylphosphonites(phosphonates)

H. Saeidian et al., Eur. J. Mass Spectrom. 19, 361–375 (2013)
365
R3
R3
R3
R3
R3
P
R1
N
N
N
OH
P
[H]
R2O
OH
[D]
R3
[F]
[E]
[G]
H
H
R3
O
R3
O
P
N
P
P
N
R1
OR2
[C]
[B]
[A]
R1
R3
OR2
R3
alpha-cleavage
-[2-(N,N-dialkylamino)ethanol]
alpha-cleavage
(-R1 )
alpha-cleavage
(-OR2 )
R1
O
R3
P
N
I
OR2
R3
beta-cleavage
-(N,N-dialkylamine)
R3
H
O
P
OH
R1
O
R1
N
P
P
PH
R1
OR2
R1
OR2
[J]
OR2
[L]
O
[K]
[I]
-alkene
-RCHO
O
O
-alkene
R1 = Et
P
P
P
R1
H
OH
R1
OH
HO
[M]
m/z 65
[N]
Figure 2. General fragmentation pattern of O-alkyl O-2-(N,N-dialkylamino)ethyl alkylphosphonites I in EI-MS.
Ions [L] and [L¢] with different structures have the same
molecular formulas and could give rise from different radical
cations. Calculations revealed that isomer [L] is 21kJmol–1
more stable than [L¢] in the case of R1 =R2 =CH3. This could be
attributed to delocalization of positive charge over two oxygen
atoms.
With these encouraging results, attention was focused
on the spectra of O-2-(N,N-diisopropylamino)ethyl
methylphosphonites (QL) and its deuterated analog (QL-d5,
entries 12 and 13 Table 1). As mentioned above, the QL is
a precursor for the synthesis of VX and its oxygen analogs.
Therefore, unambiguous identification of QL and its related
O
O
CH3
O
CH3
H3CO
P
P
N
P
N
N
OCH3
CH3
OCH3
CH3
H3C
CH3
A1
A2
A3
Figure 3. Three possible structures of [A].

366
GC/MS Studies O-2-(N,N-Dialkylamino)ethyl Alkylphosphonites(phosphonates)
CH3
H3C
N
H
H
H
H
H
HOMO
HOMO
H
H
LUMO
LUMO
O
O
H
(H3C)2N
or
P
P
OCH3
OCH3
(CN) (CO)
(CH ) (CO)
*
Figure 4. Hyperconjugation (s ® s ) in fragment ion [A].
chemicals in environmental samples is of vital interest. The
EI-MS spectra of QL and QL-d5 are shown in Figure 6. The
intensity of fragment ion [A] in both spectra, unlike the others,
is very low. Despite the other methylphosphonite derivatives,
elimination of an isopropyl radical on nitrogen from M+• was
observed with low intensity in the spectra of the QL (m/z 192)
and QL-d5 (m/z 197), respectively. These differences may be
considered as a hint for unambiguous identification of QL in
a real sample analysis.
EI-MS of O-alkyl O-2-(N,N-dialkylamino)ethyl
alkylphosphonates II
As mentioned above, the O-alkyl O-2-(N,N-dialkylamino)ethyl
alkylphosphonates II are listed in Schedule 2.B.4 of CWC. They
R3
H
R3
H
R3
R3
N
N
R3
R3
H
OH
PH
L
N
1,3 C-O hydride shift
1,4 C-P H shift
R1
O
R1
O
L
+
P
R1
OR2
PH
I
OR2
OR2
N,N-dialkylethenamine
Distonic species
R3
R3
H
R3
R3
N
N
R3
R3
H
OH
H
N
1,5 C-O H shift
1,3 C-O hydride shift
R2HO
R2O
O
L'
R2HO
O
P
+
R1
P
P
L'
I
R1
N,N-dialkylethenamine
R1
Distonic species
Figure 5. Proposed mechanisms for formation of ion [L].

H. Saeidian et al., Eur. J. Mass Spectrom. 19, 361–375 (2013)
367
114
ꢀ
100
50
0
O
O
P
N
72
M -(i -C3H7 )
127
44
84
63
56
98
91
148
176
47
134
190
119
164
220
40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230
(Spec. Edit) Scan 594 (11.921 min): 910615S3-1.D (-590)
114
ꢀ
100
50
0
D
O
O
D
P
N
D
D
D
72
127
M -(i -C3H7 )
84
44
47
64
98
56
176
148
190
159
160
225
220
40
60
80
100
120
140
180
200
240
Figure 6. EI-MS mass spectra of the QL and QL-d5.
are by-products in the synthesis of VX. Their presence in the
environmental sample indicates the alleged preparation of
restricted chemicals.
Therefore,theknowledgeontheirfragmentationmechanisms
in EI-MS spectra becomes important from the verifications
point of view for on/off site analysis. We have studied 32 O-alkyl
alkylphosphonates (Series-1, entries 1–11, Table 2), O-alkyl
O-2-(N,N-diisopropylamino)ethyl alkylphosphonates (Series-2,
entries 12–22, Table 2), and O-alkyl O-2-(N,N-dimethylamino)
ethyl alkylphosphonates (Series-3, entries 22–32, Table 2). As
typical examples, the spectra of three chemicals, along with
their deuterated analogs, are given in Figure 8. Fragment ion
O-2-(N,N-dialkylamino)ethyl alkylphosphonate MS spectra. [A] was formed by direct elimination of the alkoxy group as
The EI fragment ions of II are given in Table 2 and their routes
of fragmentation are shown in Figure 7. The M+• of II were not
present in the mass spectra. Chemical ionization (CI)-MS of
most of the studied chemicals were recorded to support their
structure elucidation (see supporting information).
a radical from M+• with moderate relative abundance. This
ion is not found in the mass spectra of series-2, with the
exception of the O-isopropyl analogs (entries 16 and 17, Table
2). However, when the O-alkyl chain on series-1 and 3 become
smaller, the intensity of the [A] signal decreases or vanishes.
Therefore, existence and intensity of [A] in the mass spectra of
II depends on the alkyl group size on the nitrogen and oxygen
atoms. Fragment [B] can be formed from M+• with double
All compounds II show fragment N-methylideneaminium [L]
as the base peak which resulted from M+• by cleavage of the
C–C bond of 2-(N,N-dialkylamino)ethanol. This ion could be
used for N,N-dialkylamino group distinction in such chemicals. hydrogen transfer (McLafferty+1 rearrangement).2 Formation
Analysis of mass spectra revealed that the type of alkyl
of ion [B] through McLafferty+1 rearrangement was proposed
groups present on nitrogen influenced the mass spectrum. by observing the corresponding fragment ions in EI-MS of
Based on the alkyl group, the chemicals can be classified in
deuterated analogs of II. This process involves an initial
three different classes: O-alkyl O-2-(N,N-diethylamino)ethyl
hydrogen migration (1,5 C–O H shift) to the oxygen-bearing

368
GC/MS Studies O-2-(N,N-Dialkylamino)ethyl Alkylphosphonites(phosphonates)
O
O
R3
P
N
R1
OR2
R3
II
-(OR2)
-(NR3R3)
McLafferty+1 rearrangement
O
R2O
HO
OH
P
OH
P
O
O
O
P
P
P
R1
R3
R1
R1
R1
R1
OH
OH
N
O
O
OR2
OH
[D]
[A]
[G]
[B]
[E]
R3
-H2O
-alkene
-H2O
O
P
O
P
-alkene
OR2
R1
R1
OH
M
[C]
[F]
-(R3)
-CH3
O
O
P
O
O
O
O
R1
R2O
R1
O
O
R1
R2O
P
P
P
R1
N
N
HN
R3
NH
R3
R'
R3
[J]
[K]
[I]
[H]
R'
R3
R3
R3
R3
R3
R3
N
N
N
[L]
[M]
[N]
Figure 7. Proposed fragmentation pathways of O-alkyl O-2-(N,N-dialkylamino)ethyl alkylphosphonates II in EI-MS.
radical cation site, leading to a distonic species. A radical
cation and a neutral enamine (radical cation–neutral complex)
are produced through single bond cleavage. Then, a hydrogen
atom transfers from an enamine to a radical cation, yielding a
cation and an enamine radical fragment (Figure 9).24
deuterated ion in the mass spectra of deuterated analogs is
an evidence of the occurrence of such a mechanism. Stepwise
expulsion of the N,N-dialkylamine moiety, which took place
to yield ion [G] and elimination of an alkene from M+•, was
another important mode of fragmentation that gave rise to
ion [D]. It is important to note that ion [D] was not produced in
It should be mentioned that the corresponding ion [B] for
compounds bearing an O-isopropyl group is not observed. all II bearing methyl groups on oxygen atoms. It is of interest
On the other hand, the b-cleavage process is observed in
that ion [D] can assume two structures, [D1] and [D2], as shown
Figure 10. Energy calculation shows that the former ion is
compounds bearing an isopropyl group on nitrogen which
can form fragment ion [K]. These facts could be used for 137kJmol–1 more stable than the latter.
identification of an isopropyl group on oxygen and nitrogen
in such chemicals. Loss of H2O from ion [B] is found in most
cases which produces the fragment ion [C]. Its corresponding
Formation of fragment ions [E] and [F] was attributed to
stepwise loss of a neutral alkene and water molecule from
ion [B]. Generally, these fragment ions were present in the

H. Saeidian et al., Eur. J. Mass Spectrom. 19, 361–375 (2013)
369

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H. Saeidian et al., Eur. J. Mass Spectrom. 19, 361–375 (2013)
371

372
GC/MS Studies O-2-(N,N-Dialkylamino)ethyl Alkylphosphonites(phosphonates)
H
O
O
HO
O
R3
O
R3
H
H
H
N
R1
P
OH
1,5 C-O H shift
P
N
P
N
R1
R1
R3
OR2
OR2
R3
R3
OR2
R3
II
Distonic species
radical cation-neutral complex
Hydrogen transfer
OH
R1
P
OH
Enamine radical fragment
+
OR2
[B]
Figure 9. Proposed mechanism for formation of ion [B] in EI-MS of II.
mass spectra of alkylphosphonates. The [M+• – R3] ions, isomeric pairs have different alkyl groups on nitrogen (entries
where the alkyl group is other than methyl, show ion [H]
corresponding to the loss of an alkyl via b-fission. Ion [H] was
1, 2 and 3, Table 3) and, hence, can easily be differentiated
from one another by considering the lower part of the mass
clearly distinguishable in the EI-MS of deuterated analogs. spectra; especially ions [L], [M] and [N], which reveal the size
As expected, [M+•-R3] is prominently observed in Series-2, in
which two isopropyl groups are attached to nitrogen. Stepwise
loss of alkoxy (OR2) and an alkyl radical on nitrogen gave
rise to the ion [I]. The cation [I] could further disintegrate by
elimination of a methyl radical and produce ion [J]. The ions
[H], [I], [J] and [K] are not present in the mass spectra of
of the alkyl group on nitrogen in the 2-(N,N-dialkylamino)
ethanol moiety. The [L] is the base peak for such chemicals
which, in the case of R3 =Et, i-Pr and Me are m/z 86, m/z 114
and m/z 58, respectively. Three other isomeric pairs (entries 4,
5 and 6, Table 3) have different alkyl groups on phosphorous
and oxygen atoms. The isomeric pairs show a resemblance in
series-3. Therefore, spectra for these chemicals are distinct. their EI-MS spectra. The mass spectra for the isomeric pair
The lower part of the spectra of all II was dominated by the
ions [L], [M], [N], [O], [P] and [Q] which were produced from
2-(N,N-dialkylamino)ethanol with hydrogen rearrangements
and alkyl and alkene elimination.
consisting of isopropyl on nitrogen (entry 4, Table 1), which
exhibit very similar appearance, are shown in Figure 11 as
example.
It is noteworthy that among the studied alkylphosphonates
II, six isomeric pairs (Table 3) are present for II. The isomerism
is exclusively due to the size of the alkyl group attached to the
nitrogen, phosphorous and oxygen atoms. These isomeric
compounds could easily be differentiated based on differences
in their EI-MS fragmentation pathways. Among these, three
Table 3. Some isomeric compounds for chemicals II.
Entry
M+•
Isomeric pairs
R2
R1
R3
1
2
3
4
5
6
209
237
223
223
251
195
CH3
C2H5
CH3
C2H5
C2H5
CH3
HO
HO
O
O
C2H5
CH3
C2H5
CH3
C2H5
i-C3H7
P
P
H3C
H3C
C2H5
C2H5
CH3
i-C3H7
C2H5
CH3
O
O
D1
CH3
C2H5
C2H5
CH3
C2H5
C2H5
O
O
P
CH2
H3C
P
O
CH3
C2H5
C2H5
CH3
i-C3H7
i-C3H7
H3C
O
D2
OH
OH
CH3
C2H5
C2H5
CH3
CH3
CH3
Figure 10. Proposed structures of [D].

H. Saeidian et al., Eur. J. Mass Spectrom. 19, 361–375 (2013)
373
114
ꢀ
100
50
0
[D], m/z 123
O
O
HO
P
N
P+
O
O
70
O
84
127
43
79
98
56
208
236
151
164
134
140
176 192
180
225
220
40
60
80
100
120
160
200
240
(Text File) Scan 687 (14.508 min): 910307S2-1.D (-680)
114
ꢀ
[C], m/z 107
100
O
O
P+
O
P
N
O
O
70
50
84
127
43
47
79
56
151
98
208
236
240
134
140
161 173
160 180
192
200
0
40
60
80
100
120
220
Figure 11. EI mass spectra for isomeric pair consisting isopropyl on nitrogen (entry 5, Table 3).
The ion at m/z 107 corresponding to the fragment of [C]
proves to be characteristic for the methyl moiety on the oxygen
and McLafferty+1 rearrangement. The most important frag-
ment ion in the EI-MS of phosphonites was formed through
atom in such chemicals and the presence of ion [D] in the a-cleavage a P−C bond, which was clearly distinguishable in
mass spectra of chemicals shows methyl attached to the
phosphorous atom. Analysis of mass spectra of deuterated
analogs also supported these points.
the spectra of the deuterated analogs. This fragment ion was
not observed in the mass spectra of phosphonates. Presence
and abundance of fragment ions formed through direct elimi-
nation of alkoxy groups in the mass spectra of phosphonates
depends on the alkyl group size on nitrogen and oxygen atoms.
The characteristic fragmentation processes and subtle differ-
ences in EI-MS spectra of phosphonites and phosphonates
Conclusions
EI-MS of the O-alkyl O-2-(N,N-dialkylamino)ethyl alkyl- may create pitfalls in structural assignments of unknown
phosphonites(phosphonates) were collected and investigated
with the aim of enriching OCAD, which may be used in OPCW
verification activities, on/off site analysis and to improve MS
interpretation knowledge. The presented EI-MS data of the title
chemicals indicated that their fragmentations were governed
by the size and structure of the alkyl group attached to nitrogen,
phosphorus and oxygen atoms. Fragmentation processes
CWC-related chemicals and isomeric compounds.
Appendix A. Supplementary
data
were mostly dominated by hydrogen rearrangement, alkene, Supplementary data associated with this article can be found,
amine and alkoxy elimination by a- and b-cleavage process in the online version, at http://dx.doi.org/10.1255/ejms.1234.

374
GC/MS Studies O-2-(N,N-Dialkylamino)ethyl Alkylphosphonites(phosphonates)
2007(15), 171 (2007). doi: 10.3998/ark.5550190.0008.
f17
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