Analysis of chemical neutralization products of phosphonothiolates by gas chromatography mass spectrometry

Article abstract of DOI:10.1080/10426500307845

A series of phosphonothiolates, including the highly toxic O-Ethyl-S-(2-diisopropylamino) ethyl methylphosphonothioate (VX), have been subjected to chemical neutralization reaction with metallic sodium. The phosphonothiolates decompose to their respective phosphonic and phosphonothioic acids and this results in the detoxification of VX. GC/MS technique in both EI and CI mode has been applied for reaction monitoring and final identification of the neutralization products formed in this reaction.

Full text of DOI:10.1080/10426500307845

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Phosphorus, Sulfur, and Silicon and the Related
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Analysis of Chemical Neutralization Products of
Phosphonothiolates by Gas Chromatography Mass
Spectrometry
A. K. Gupta a , M. Palit a , D. K. Dubey a & S. K. Raza a
a Defence Research & Development Establishment , Gwalior, India
Published online: 27 Oct 2010.
To cite this article: A. K. Gupta , M. Palit , D. K. Dubey & S. K. Raza (2003) Analysis of Chemical Neutralization Products of
Phosphonothiolates by Gas Chromatography Mass Spectrometry, Phosphorus, Sulfur, and Silicon and the Related Elements,
178:8, 1631-1637, DOI: 10.1080/10426500307845
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Phosphorus, Sulfur, and Silicon, 178:1631–1637, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390225597
ANALYSIS OF CHEMICAL NEUTRALIZATION
PRODUCTS OF PHOSPHONOTHIOLATES BY GAS
CHROMATOGRAPHY MASS SPECTROMETRY
A. K. Gupta, M. Palit, D. K. Dubey, and S. K. Raza
Defence Research & Development Establishment, Gwalior, India
(Received November 27, 2001; accepted February 24, 2002)
A series of phosphonothiolates, including the highly toxic O-Ethyl-S-(2-
diisopropylamino) ethyl methylphosphonothioate (VX), have been sub-
jected to chemical neutralization reaction with metallic sodium. The
phosphonothiolates decompose to their respective phosphonic and phos-
phonothioic acids and this results in the detoxification of VX. GC/MS
technique in both EI and CI mode has been applied for reaction moni-
toring and final identification of the neutralization products formed in
this reaction.
Keywords: Chemical ionization; chemical neutralization; disulphide;
electron ionization; GC/MS; phosphonic acid; phosphonothiolates;
sodium; thiophosphonic acid; VX
Chemical warfare agents either can be destroyed by incineration or
neutralized by chemical reaction to produce nonlethal or nontoxic
products, which can be disposed of safely, or postprocessed.1 O-Alkyl
methylphosphonothiolates constitute one of the most lethal classes
of “nerve agents” represented by O-ethyl S(2-diisopropylamino)ethyl
methylphosphonothiolate commonly known as VX (1) which is a highly
toxic chemical and can stop respiratory and nervous functions and can
kill in minutes.2
VX can be neutralized effectively by the use of bleach at low pH,
where VX readily dissolves in acidic solutions; on the other hand the sol-
ubility of VX is reduced significantly at higher pH. Hydrolysis catalyzed
The authors thank Dr. D. K. Jaiswal, Director, DRDE and Dr. M. P. Kaushik, Head
PTD Division for providing necessary facilities and encouragement.
Address correspondence to S. K. Raza, Defence Research & Development Establish-
ment, Gwalior-474 002, India. E-mail: skraza@hotmail.com
1631

1632
A. K. Gupta et al.
by base is one of the most widely used neutralization reaction for nerve
agents. VX (pKa = 9) dissolves in pure water to form a basic solution
and the solubility of VX decreases significantly as the solution becomes
more basic, leading to very slow rate of hydrolysis.3 Another approach
for the neutralization of VX is oxidation of the sulfur atom. But on oxi-
dation, nitrogen present in VX is predominantly oxidized to the stable
N-oxide, which is still toxic.4 Thus, the neutralization of VX by oxida-
tion is not the method of choice. Nano-size MgO, CaO, and Al2O3 also
have been used for the neutralization of VX.5−7 These reactions are
analogous to their solution behavior,3 with two exceptions: The first is
that the corresponding nontoxic phosphonate products reside as sur-
face bound complexes; the second, and most notable exception, is that
toxic EA-2192 which forms under basic hydrolysis8,9 is not observed in
these reactions. VX also has been neutralized and decontaminated by
using metal ions supported on zeolites. Silver and sodium exchanged
zeolites have been used to enhance the rate of decomposition of VX
and related compounds at ambient temperature.10,11 Recently, desul-
furization of alkyl and alkyl-aryl organ sulfur compounds with sodium
was reported resulting in the formation of corresponding alkanes and
small amounts of alkylmercaptans.12 Our interest in detoxification of
highly-toxic VX and related phosphonothiolates prompted us to apply
this method for the chemical neutralization of these compounds. In this
study we selected VX (1), and some structurally related phosphonoth-
iolates as shown in Figure 1.
RESULTS AND DISCUSSION
The total chemical neutralization was achieved within 120 min. The
chemical neutralization of VX (1) yielded nontoxic products namely
N,N-diisoprylaminoethyl disulfide (1a), methylphosphonic acid (1b),
O-ethyl methylphosphonic acid (1c), methylthiophosphonic acid (1d),
and O-ethyl methylthiophosphonic acid (1e). All the phosphonic acids
were identified as their trimethylsilyl derivatives both in EI and CI
modes. 1a was observed only while monitoring the neutralization reac-
tion with GC/MS-EI, but after doing the work-up of the reaction mix-
ture, 1a could not be detected either in organic or aqueous layer. This
may have been due to further desulfurization.
The neutralization of S,S-dialkyl alkylphosphonothiolates (2–8)
produced their respective disulfides (2a–8a), alkylphosphonic acids
(2b–8b), and alkylthiophosphonic acid (2c–8c). The acids were identi-
fied on the basis of EI and CI data of their silylated derivatives. In 5 we
detected S-butyl isopropylthiophosphonic acid (5d) as its trimethylsilyl

Analysis of Chemical Neutralisation
1633
FIGURE 1 Structures of phosphonothiolates subjected to chemical neutral-
ization reaction.
derivative which was formed most probably due to incomplete desul-
phurisation.
The neutralization reaction of S,S-dipropyl methylthiophosphonoth-
iolate (9) yields not only its corresponding disulfide (9a) but also tri-
and tetra-sulfides (9b and 9c) respectively. The other neutralization
products obtained from 9 were methylthiophosphonic acid (9d) and
methyl phosphonic acid (9e) identified as their trimethylsilyl deriva-
tive by GC/MS.
In all these neutralization reactions, we observed disulfides only
while monitoring the reaction products before work-up; however, af-
ter giving extended reaction time or after the addition of methanol,
these disulfides disappear and only corresponding alkylphosphonic
acids and alkylthiophosphonic acids were detected by GC/MS as their

1634
A. K. Gupta et al.
FIGURE 2 Products obtained on chemical neutralization reaction of 1–9 as
confirmed by GC/MS.

Analysis of Chemical Neutralisation
1635
TABLE I EI and CI MS Data of the Compounds Detected from Chemical
Neutralization of 1–9
Molecular
weight
CI MS
Compd. no.
EI mass spectrum (m/z)
(M + H)+
1a
320
240
42, 72, 89, 114 (100%), 160, 174, 189, 285
59, 73, 105, 133, 147, 181, 209, 225 (100%),
321
241
1b, 2b, 9d
240 (M+.
)
1c
196
256
212
178
150
254
61, 75, 121, 137, 153 (100%), 169, 181, 196 (M+.
73, 93, 113, 133, 147, 241 (100%), 256 (M+.
56, 73, 121, 137, 153, 169 (100%), 197, 212 (M+.
57, 87, 122, 178 (100%), (M+.
66, 78, 108, 150 (100%) (M+.
73, 121, 135, 147, 195, 211, 226, 239 (100%),
)
)
197
257
213
179
151
255
1d, 2c, 9e
1e
2a, 3a, 4a, 5a
6a, 7a, 8a, 9a
3b, 6b
)
)
)
254 (M+.
)
4b, 7b
5b, 8b
5d
9b
9c
268
268
284
182
214
73, 135, 195, 211, 225, 237, 253 (100%), 268 (M+.
73, 135, 147, 195, 211, 226, 253 (100%), 268 (M+.
73, 121, 133, 147, 209 (100%), 242, 269, 284 (M+.
)
)
)
269
269
285
183
215
55, 64, 100, 111, 140, 182 (100%) (M+.
)
65, 70, 104, 130, 142, 193, 214 (100%) (M+.
)
trimethylsilyl derivatives. The disulphides perhaps undergo further
desulfurization to give alkenes, which were not detected. The EI and
CI mass spectral data of various phosphonothiolates obtained from the
neutralization reaction are presented in Table I.
Chemical neutralization with sodium metal may thus be a useful re-
action for the complete decontamination of thiophosphonates including
the highly toxic compounds such as VX. The mass spectral data in both
EI and CI for various degradation products can be used for the detection
of the compounds even in the reaction mixture.
EXPERIMENTAL
Synthesis of Phosphonothiolates
O-Ethyl-S- [2-(diisopropylamino) ethyl] methylphosphonothiolate (VX)
was synthesized inhouse according to literature procedure13 and the
final structure and purity was checked by GC/MS and 1H-NMR. (Cau-
tion: VX is synthesized in a special laboratory, built mainly for synthe-
sis of highly-toxic compounds. Full body protection including breathing
protection is worn when handling the agent, which includes both syn-
thesis work and the neutralization reaction.)
Dialkyl alkylphosphonothiolates (2–8) and dialkyl alkylthiophos-
phonothiolate (9) were synthesized according to the literature

1636
A. K. Gupta et al.
procedure14−16 and the final structure and purity were checked by
GC/MS and 1H-NMR.
Desulphurization Reaction
Sodium (0.1 mmol) and phosphonothiolates (0.01 mmol) were taken in
a solvent (10 mL) [decane for 1, 2, 5 and dodecane for 3, 4, 6–9] in a
50 mL two-necked, round-bottom flask fitted with a condenser. The re-
action mixture, monitored by GC/MS in EI mode, was vigorously stirred
and refluxed till the substrate was totally consumed. After cooling the
reaction mixture to room temperature, unreacted sodium was destroyed
with methanol at 0◦C. Saturated aqueous NH4Cl (50 mL) was added to
the mixture.
Extraction and Derivatization
After the addition of saturated aqueous NH4Cl solution, the aqueous
and organic layers were separated using separating funnel. The organic
layer was analyzed by GC/MS in both EI and CI modes as such while
the aqueous layer was extracted with diethyl ether and analyzed after
concentration. This layer was later silylated with BSTFA at 80◦C for
120 min and subjected to GC/MS analysis.
One portion of the aqueous layer was evaporated to dryness
on rotavapour followed by reconstitution with acidic methanol
(HCl/methanol −0.5N). It was further evaporated to dryness and sily-
lated for GC/MS analysis. Another portion of the aqueous layer after
evaporation to dryness was reconstituted with alkaline methanol (1%
triethylamine/methanol). It was further evaporated to dryness and sily-
lated for GC/MS analysis.
GC/MS Analysis
The GC/MS analyses were performed by Varian 3400 GC coupled to a
TSQ 7000 mass spectrometer (Finnigan Mat). GC operating conditions
were as follows: injector temperature 250◦C, transfer line temperature
280◦C, column temperature programming 50◦C (2 min)—@10◦C/min-
280◦C (5 min), carrier gas helium at pressure of 10 psi. EI mass spec-
trometric operating conditions were as follows: ion source pressure
1.5 × 10−6 torr, source temperature 150◦C, electron energy 70 eV, and
emission current 400 µA. CI mass spectrometric operating conditions
were as follows: ion source pressure with methane as the reagent gas
1.5 × 10−3 torr, source temperature 150◦C, electron energy 100 eV, and
emission current 300 µA.

Analysis of Chemical Neutralisation
1637
REFERENCES
[1] Yu-Chu Yang, Chemistry and Industry, 334 (1995).
[2] J. A. F. Compton, in Military Chemical and Biological Agents, Chemical and
Toxicological Properties (The Telford Press, Caldwell, NJ, 1987).
[3] Y.-C. Yang, J. A. Baker, and J. R. Ward, Chem. Rev., 92, 1729 (1992).
[4] Y.-C. Yang, L. L. Szafraniec, W. T. Beaudry, and D. K. Rohrbaugh, J. Am. Chem.
Soc., 112, 6621 (1990).
[5] G. W. Wagner, P. W. Bartram, O. Koper, and K. J. Klabunde, J. Phys. Chem. B, 103,
3225 (1999).
[6] G. W. Wagner, O. Koper, E. Lucas, S. Decker, and K. J. Klabunde, J. Phys. Chem. B,
104, 5118 (2000).
[7] G. W. Wagner, L. R. Procell, R. J. O’Connor, S. Munavalli, C. L. Carnes, P. N. Kapoor,
and K. J. Klabunde, J. Am. Chem. Soc., 123, 1636 (2001).
[8] Y.-C. Yang, Acc. Chem. Rev., 32, 109 (1999).
[9] Y.-C. Yang, L. L. Szafranine, and W. T. Beaudry, J. Org. Chem., 58, 6964 (1993).
[10] A. Bellamy, J. Chem. Soc., Perkin Trans. 2, 2325 (1994).
[11] G. W. Wagner and P. W. Bartram, Langmuir, 15, 8113 (1999).
[12] Zhengkun Yu and J. G. Verkade, Tet. Lett., 39, 2671 (1998).
[13] F. Siegfried, Lehrbuch der Militarchemie, Band 1-2, 2 ueberarb. Aufl.; militarverlag
der DR: Berlin, 1977.
[14] E. Schegk, H. Schlor, and G. Schrader, DAS 1, 058, 992 (1957).
[15] G. Schrader, DAS 1, 032, 247 (1954).
[16] K. N. Anisimov, N. E. Kolobova, and A. N. Nesmejanov, Izv. Akad-Nauk SSSR, Ser.
Khim., 669 (1955).