J . Org. Chem. 1996, 61, 8407-8413
8407
Au toca ta lytic Hyd r olysis of V-Typ e Ner ve Agen ts
Yu-Chu Yang,* Linda L. Szafraniec, William T. Beaudry, Dennis K. Rohrbaugh,
Lawrence R. Procell, and J ohn B. Samuel
Research and Technology Directorate, U.S. Army, Edgewood Research, Development, and Engineering
Center (ERDEC), Aberdeen Proving Ground, Maryland 21010-5423
Received J uly 30, 1996X
Both V-type nerve agents MeP(O)(OR)(SCH2CH2NR′2), VX (R ) C2H5; R′ ) i-C3H7) and its isomeric
analog RVX (the “Russian V-agent”, R ) i-C4H9; R′ ) C2H5), react slowly but completely with an
equimolar amount of H2O via exclusive P-S cleavage to produce the corresponding phosphonic
acid (MeP(O)(OR)OH) and 2-aminoethanethiol (HSCH2CH2NR′2). The reaction is believed to be
initiated by nucleophilic attack of the deprotonated phosphonic acid on the protonated V-agent to
produce a diphosphonate intermediate ((MeP(O)(OR))2O) that rapidly hydrolyzes to regenerate the
phosphonic acid. The autocatalytic ionic chain reaction is thus continued in the nearly nonaqueous
reaction medium. The viscous final product mixture remains reactive toward freshly added trace
amounts of the V-agent, giving the same final reaction half-life of 13-15 h at 23 °C. When water
is insufficient and depleted, the diphosphonate intermediate accumulates and reacts with the
aminoethanethiol to regenerate the V-agent. This autocatalytic hydrolysis process is not observed
with a simpler phosphonothioate analog (MeP(O)(OC2H5)(SC2H5)), which suggests that the attack
of the phosphonic acid on the V-agent is intramolecularly assisted by the protonated amino group.
In tr od u ction
VX (O-ethyl S-(2-(diisopropylamino)ethyl) methyl-
phosphonothioate, CAS No. 50782-69-0) has been known
to slowly degrade in storage to ethyl methylphosphonic
acid, 2-(diisopropylamino)ethanethiol, and the toxic P,P′-
diethyl dimethyldiphosphonate (1a , 1d , and 1c in Scheme
1, respectively) in the presence of trace amounts of
water.7 The following short-term laboratory observation
also confirmed this degradation. A freshly prepared
94.9% pure VX sample (feed 1, no inhibitor added, see
the following discussion) was stored in a capped NMR
tube placed in an oven at 35 °C and was analyzed by 31P
NMR once a week. After 3 weeks, the major degradation
product 1c increased from less than 0.6 to 2.6 area %;
about 0.2 area % 1a was also detected; and the purity of
the VX decreased to 92.1%. In practice, 2-5% by weight
of an inhibitor, diisopropyl- or dicyclohexylcarbodiimide
(i-PrNdCdNiPr (DICDI) or C6H11NdCdNC6H11(DCCDI))
was added to the stockpiled VX to retard the degradation.
The inhibitor can react with H2O, 1a , and 1d to form urea
and thiourea (Table S-4, Supporting Information), so that
further degradation of VX is prevented.7
There has been a heightened interest in the chemistry
of chemical warfare agents since the National Research
Council recommended chemical neutralization as one of
the potential alternative methods for the destruction of
chemical weapons.1 Of the known weaponized nerve
agents, the relatively new V-type agents, methyl phospho-
nothioates (MeP(O)(OR)(SCH2CH2NR′2) are among the
most toxic and persistent.2,3 Thousands of tons of two
isomeric V-agents have been declared as stockpiles in two
countriessVX (1, R ) Et; R′ ) i-Pr) in the United States
and RVX (“the Russian V-agent”, 2, R ) i-Bu; R′ ) Et)
in Russia.4,5 These stockpiles are to be destroyed in the
near future, and the safety as well as environmental
impacts of the destruction process are of ultimate con-
cern.1 We present in the following an NMR study of
the background chemistry of a simple neutralization
approachsto detoxify the V-agents by adding about 7%
water (equimolar) to the V-agent in a closed container.
Our small-scale (up to 50 mL) experiments showed that
in 30-60 days at room temperature, the V-agents were
completely converted to less toxic products by a unique
autocatalytic hydrolysis process.6 Thus, any conceivable
human or environmental exposures to these exceedingly
lethal compounds during neutralization are minimal, and
the total mass of the final neutralized product is only
increased by less than 10% over the agent feed.
It is conceivable that if a small but sufficient (i.e.,
stoichiometric) amount of water is deliberately added to
VX, both VX and 1c should continue to hydrolyze to
completion giving only two nontoxic final products, 1a
and 1d . It may be possible to develop a large-scale
process that chemically neutralizes the V-agent stockpiles
in-situ (i.e., inside the original container). Therefore, we
have investigated the reaction of both VX and RVX (O-
isobutyl S-(2-(diethylamino)ethyl) methylphosphonothio-
ate, CAS No. 159939-87-4) with up to 10% watersan
equimolar mixture gives H2O/V-agent ) 0.067 g/g. We
have also studied a simple thioate analog, O,S-diethyl
methylphosphonothioate (3, MeP(O)(OC2H5)(SC2H5)), un-
der comparable reaction conditions to isolate the effect
X Abstract published in Advance ACS Abstracts, November 15, 1996.
(1) Committee on Review and Evaluation of the Army Chemical
Stockpile Disposal Program, National Research Council. Recommenda-
tions for Disposal of Chemical Agents and Munitions; National
Academy Press: Washington, D. C., 1994.
(2) Yang, Y.-C.; Szafraniec, L. L.; Beaudry, W. T.; Rohrbaugh, D.
K. J . Am. Chem. Soc. 1990, 112, 6621-6627.
(3) Yang, Y.-C.; Baker, J . A.; Ward, J . R. Chem. Rev. 1992, 92, 1729-
1743.
(4) (a) Voronov, V.; Fedorov, L. Chemical Weapons or Chemical War?
Moscow Khim. Zh. 1993, J uly, No. 7, 66-70. (b) Beletskaya, I. P.;
Novikov, S. S.; Chemical Weapons in Russia. Vestn. Ross. Akad. Nauk
1995, 65(2), 99-104.
(5) Mendeleev Chemistry J ournal (Zhurnal Ross. Khim. Ob-va im.
D. I. Mendeleeva); Allerton Press, New York, 1993; Vol. 38, No. 2.
(6) Yang, Y.-C. Chem. Ind. 1995, No. 9, 334-337.
(7) The observed degradation did not result from air oxidation or
from thermal decomposition as was verified by monitoring VX samples
under both wet and dry nitrogen at 100 °C. See: Rohrbaugh, D. K.; et
al. Studies in Support of SUPLECAM II. 1. Thermal Decomposition of
VX, CRDEC-TR-88056, May 1988, Aberdeen Proving Ground, MD,
unclassified report.
S0022-3263(96)01450-8
This article not subject to U.S. Copyright. Published 1996 by the American Chemical Society