Reaction of lewisite-1 with alcohols, diols, and thiols in water - A simple method of derivatization of thiodiglycol

Article abstract of DOI:10.1080/10426500701429197

Reaction of 2-chlorovinyldichloroarsine (Lewisite-1) with alcohols, thiols, diols, and hydroxy thiols in water at 40C has been examined. The expected derivatization products, dialkyl 2-chlorovinylarsonites or corresponding arsonodithiolites, were obtained with alcohols and thiols, whereas reactions with bifunctional diols and hydroxythiols produced analogous cyclic esters. All derivatives may be easily detected using gas chromatography. This reaction was found useful to easily transform bis(2-hydroxyethyl) sulfide (thiodiglycol), a sulfur mustard decomposition product, to a stable eight-membered cyclic arsonite derivative. After extraction with dichloromethane, the derivative may be easily and selectively detected using GC/MS at a 100 ppb level thiodiglycol content in water matrices, eliminating tedious evaporation of water and then silylation. This method may be applied to analyze Chemical Weapons Convention related environmental water samples.

Full text of DOI:10.1080/10426500701429197

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Phosphorus, Sulfur, and Silicon
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Reaction of Lewisite-1 with
Alcohols, Diols, and Thiols in
Water—A Simple Method of
Derivatization of Thiodiglycol
Mieczysław S. Sokołowski a & Leszek Konopski a
a Organization for the Prohibition of Chemical
Weapons , OPCW Laboratory , Rijswijk, The
Netherlands
Published online: 23 Aug 2007.
To cite this article: Mieczysław S. Sokołowski & Leszek Konopski (2008) Reaction
of Lewisite-1 with Alcohols, Diols, and Thiols in Water—A Simple Method of
Derivatization of Thiodiglycol, Phosphorus, Sulfur, and Silicon and the Related
Elements, 182:10, 2311-2327, DOI: 10.1080/10426500701429197
To link to this article: http://dx.doi.org/10.1080/10426500701429197
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Phosphorus, Sulfur, and Silicon, 182:2311–2327, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701429197
Reaction of Lewisite-1 with Alcohols, Diols, and Thiols
in Water—A Simple Method of Derivatization
of Thiodiglycol
Mieczyslꢀaw S. Sokolꢀowski
Leszek Konopski
Organization for the Prohibition of Chemical Weapons, OPCW
Laboratory, Rijswijk, The Netherlands
Reaction of 2-chlorovinyldichloroarsine (Lewisite-1) with alcohols, thiols, diols,
and hydroxy thiols in water at 40◦C has been examined. The expected derivati-
zation products, dialkyl 2-chlorovinylarsonites or corresponding arsonodithiolites,
were obtained with alcohols and thiols, whereas reactions with bifunctional diols
and hydroxythiols produced analogous cyclic esters. All derivatives may be eas-
ily detected using gas chromatography. This reaction was found useful to easily
transform bis(2-hydroxyethyl) sulfide (thiodiglycol), a sulfur mustard decomposi-
tion product, to a stable eight-membered cyclic arsonite derivative. After extraction
with dichloromethane, the derivative may be easily and selectively detected using
GC/MS at a 100 ppb level thiodiglycol content in water matrices, eliminating te-
dious evaporation of water and then silylation. This method may be applied to
analyze Chemical Weapons Convention related environmental water samples.
Keywords Alcohols; derivatization; diols; gas chromatography; lewisite; thiodiglycol
INTRODUCTION
2-Chlorovinyldichloroarsine (Lewisite-1 or L1, 1), usually contain-
ing varying amounts of its analogs: bis(2-chlorovinyl)chloroarsine
(Lewisite-2, 2) and tris(2-chlorovinyl)arsine (Lewisite-3, 3), is a com-
pound listed in Schedule 1 of toxic chemicals in the Annex on Chem-
icals of the Chemical Weapon Convention (CWC).1 Despite of its rel-
atively low polarity, L1 is not easily separated using gas chromatog-
raphy except at a very high concentration level. However, Lewisite-1
easily reacts with alcohols2 and thiols3 in organic solvents, as acetone,
producing appropriate esters or thioesters of 2-chlorovinylarsonic acid.
Received April 14, 2007; accepted April 22, 2007.
We would like to thank Dr. Peter Siegenthaler for performing the NMR spectra.
Address correspondence to Mieczyslꢀaw S. Sokolꢀowski, OPCW Laboratory, Heulweg 28-
30, Rijswijk, GN 2288, The Netherlands. E-mail: opcwrij@worldonline.nl
2311

2312
M. S. Sokolꢀowski and L. Konopski
Only the reaction of L1 with one of the thiols, methyl thioglycolate (HS-
CH2COOMe, 4) has been reported to proceed in water at 60–70◦C.4 To
our best knowledge, no reaction of Lewisites with alcohols in water has
been described in the literature as yet.
Reactions with dithiols could be performed in both organic solvents
and water. Thus, 1,2-ethanedithiol 5,5−10 1,3-propanedithiol 65,6,10,11
and their homologues up to 1,8-octanedithiol6 in water, ethanol, 2-
propanol or acetone, as well as 3,4-dimercaptotoluene (DMT 7)10,12
in hexane transform L1 into appropriate 5- to 11-membered cyclic
thioesters, which are stable derivatives and easy to identify on GC/MS.
Also 1,2-propanedithiol (British anti-Lewisite, BAL 8) reacts with
Lewisite-1 in water to form a stable and non-toxic 5-membered ar-
sonodithiolite, preventing the toxic Lewisite effects.10,13 However, to
our knowledge, no reaction of Lewisites with diols and hydroxy thiols
in water has been described in the literature as yet.
Analyzing water samples containing low concentrations of compound
1 and some C6-C10 alcohols, we unexpectedly found the reaction prod-
ucts of L1 and alcohols.14 That is why we decided to investigate this
reaction.
Bis(2-hydroxyethyl) sulfide (thiodiglycol, TDG, 9) is the most impor-
tant sulfur mustard decomposition product, as well as a starting mate-
rial for its production, a compound listed in Schedule 2 of toxic chemicals
in the Annex on Chemicals of the CWC.1 Due to its high polarity and the
absorptive nature, TDG is not extractable from water or soil using an
organic solvent, except at a very high concentration, for the same rea-
son it is also not easy to analyze it directly using GC.15 As described in
the literature procedures,14,16 the water solution has to be evaporated
to dryness using for example rotating vacuum evaporator,17 following
by silylation with N,O-bis(trimethylsilyl) trifluoroacetamide (BSTFA)
in tetrahydrofuran and identification on GC/MS as a bis(trimethylsilyl)
derivative.15 This arduous and time consuming procedure often did not
give a satisfactory recovery and was basically developed to confirm pres-
ence of TDG in an aqueous sample at the 10 ppm (μg/g) level. However,
a solid phase micro extraction (SPME) method allowed the GC/MS de-
tection of TDG in water at a 200 ppb level as tert-butyldimethylsilyl
derivative, obtained from N-methyl−N-(tert-butyldimethylsilyl) triflu-
oroacetamide (MTBSTFA).18 Other developed methods of TDG derivati-
zation were pentafluorobenzoylation14 or acylation with heptafluorobu-
tyric anhydride.19
In this article, reaction of Lewisite-1 1 with different primary alco-
hols, thiols, diols (including TDG) and hydroxy thiols in water has been
examined, and the resulting products were analysed using GC/MS and
GC/FID/FPD.

Reaction of Lweisite-1 with Alcohols, Diols, and Thiols
2313
TABLE I Derivatives of 2-Chlorovinylarsonous Acid and Alcohols or
Thiols
Chemical name
M.w. (m/z)
RI
10
11
12
13
14
15
16
17
18
O,O-dimethyl 2-chlorovinylarsonite
O,O-diethyl 2-chlorovinylarsonite
198
226
226
240
240
254
254
282
314
1018
1136
1198
1167
1221
1271
1309
1491
1933
O-methyl O-isopropyl 2-chlorovinylarsonite
O-ethyl O-isopropyl 2-chlorovinylarsonite
O-ethyl O-propyl 2-chlorovinylarsonite
O,O-diisopropyl 2-chlorovinylarsonite
O,O-dipropyl 2-chlorovinylarsonite
O,O-dibutyl 2-chlorovinylarsonite
S,S−dibutyl 2-chlorovinylarsonodithiolite
RESULTS AND DISCUSSION
The derivatives 10–24 of Lewisite-1 with alcohols, thiols and glycols,
obtained according to procedures described in the experimental section,
are presented in Tables I and II. In water solution, Lewisite-1 undergoes
complex transformations, depending on pH. Only if pH is lower than
2 and in presence of hydrochloric acid, Lewisite-1 is expected to exist
mainly in its form 1 in water solution.
In weakly acidic and neutral water solutions, Lewisite-1
has tendency to hydrolyze affording 2-chlorovinylarsonous acid
L1(OH)225.10,20 This acid is in equilibrium with its anhydride, called
Lewisite-1 oxide, with a formal structure Cl CH CH As O 26. At
higher concentration levels, this anhydride exists, however, mainly
in different polymeric or oligomeric forms,10 the most common is
the trimeric form, 2,4,6-tris(2-chlorovinyl)-1,3,5-trioxa-2,4,6-triarsane
(L1-O)3, (26a). This form is non polar (easy to extract from water
solutions with dichloromethane), volatile and can be identified by
gas chromatograph with a reasonable retention time under standard
TABLE II Cyclic Derivatives of 2-Chlorovinylarsonous Acid
Chemical name, acronym
M.w. (m/z)
RI
19
20
21
22
2-(2-chlorovinyl)-1,3,2-dioxarsole, L1=EG
2-(2-chlorovinyl)-1,3,2-oxathiarsole, L1=2-ME
2-(2-chlorovinyl)-1,3,6,2-dioxathiarsocane, L1=TDG
2-(2-chlorovinyl)-1,3,9-trioxa-6,12-dithia-2-
arsacyclotetradecane, L1=(TDG)2
196
212
256
360
1129
1345
1656
2455
23
24
2-(2-chlorovinyl)-1,3,6,7,2-dioxadithiarsonane, L1=SS
2-(2-chlorovinyl)-1,3,6,2-trioxarsocane L1=DEG
288
240
1910
1438

2314
M. S. Sokolꢀowski and L. Konopski
conditions (RI = 2177). The homologous tetrameric form – (L1-O)4
26b may be only observed on LC, and possibly some other in water
and organic solvents insoluble10 higher cyclic or linear polymers may
also form; they were not examined in this work however. Moreover,
an acetylene elimination in a retro-Michael reaction may be also
observed.21,22 The resulting chloroarsenous acid derivative dehydrates
and eliminates HCl affording arsenic(III) oxide As4O6 (27). This
relatively volatile—even though polar—inorganic compound is always
present in all gas chromatograms as a broad peak (RI = 1427) and
produces a characteristic mass spectrum in GC/MS (M+. at m/z 396);
the decomposition may also occur in the GC injector.
In alkaline solution, the retro-Michael elimination occurs already
quantitatively, 2-chlorovinylarsonic acid loses an acetylene HC CH 28
molecule,21,22 and due to alkaline conditions, the resulting chloroarse-
nous acid is at the same time transformed into its disodium salt afford-
ing disodium chloroarsenite 29. At higher pH, the remaining chlorine
atom hydrolyses and finally only trisodium arsenite (Na3AsO3, 30) is
present in the water solution (Scheme 1).
Reactions of Lewisite-1 with C1-C4 aliphatic alcohols were first ex-
amined. The reactions were carried out at 40◦C during 2 to 3 h with
diluted solution of the appropriate alcohol (50 ppm, m/m) and Lewisite-
1 (250 ppm) in water. The reactions with mixtures of alcohols were also
carried out in such a way as to maintain fivefold excess of L1 with re-
spect to every alcohol, present at 50 ppm level. The examined alcohols
methanol 31, ethanol 32, propanol 33, isopropanol 34, and butanol 35
SCHEME 1 The transformations of Lewisite-1 in water.

Reaction of Lweisite-1 with Alcohols, Diols, and Thiols
2315
afforded the appropriate O,O-dialkyl 2-chlorovinylarsonites 10–17, de-
tected on GC/MS (Scheme 2). The extension of the reaction time de-
creased the yield of the derivative and after 17 h (overnight) there
was no derivatisation product detected on GC/MS. Thus the dialkyl
2-chlorovinylarsonites and especially the esters of lower alcohols, were
not stable.
Since arsenic shows a high affinity to sulfur, it may be expected that
derivatization of Lewisite-1 in water with a thiol proceeds faster, even
if there is neither dichloroarsine form 1 nor Lewisite-1 oxides (such as
(L1-O)3, 26a) present in the water solution. Thus, both forms 1 and 26a
were carefully removed from the Lewisite-1 water solution by washing
with dichloromethane, and only 2-chlorovinylarsonous acid L1(OH)2 25
(250 ppm) was practically present in water. Reaction with 1-butanethiol
36 (250 ppm) in water at room temperature during 10 min smoothly
transformed the arsonous acid form of Lewisite-1 25 into S, S−dibutyl
2-chlorovinylarsonodithiolite 18.
However, the same reaction of L1(OH)2 25 with propanol 33 carried
out at 40◦C did not produce O,O-dipropyl 2-chlorovinylarsonite 16 even
after 17 h. Thus, Lewisite-1 reacts with alcohols in water only in its
anhydride form (L1-O)3 26a, and—of course—in dichloroarsine form 1,
whereas reaction with thiols occurs easily with all forms existing in
water, including 2-chlorovinylarsonous acid 25.
The retention indices (RIs) of the 2-chlorovinylarsonous acid esters
obtained are presented in Table I.
EI MS spectra of the dialkyl 2-chlorovinylarsonites 10–17 contain oc-
casionally a very weak peak for the molecular ion, but usually no peak
for this ion at all. In most cases, the [M-·OR]+ is the base ion, except
for O,O-dimethyl 2-chlorovinylarsonite 10, where the characteristic
SCHEME 2 Reactions of Lewisite-1 with alcohols and 1-butanethiol.

2316
M. S. Sokolꢀowski and L. Konopski
Cl CH CHAsH(OMe)+· ion at m/z 168 and the [M-CH2O]+· ion are ob-
served instead. The ions As(OMe2)+ at m/z 137 and HAs=O+Me at m/z
107 give the most intense signals present in the spectrum. In the case
of the isopropyl esters, also the [M-·CH3]+ ion is found. Characteristic
As(OR2)+ ions also are found in all spectra. Ions Cl CH CH As O+R,
Cl As O+R (acetylene elimination), HO As O+H at m/z 109, AsC2H2+
at m/z 101, As O+ at m/z 91 and characteristic As+ (no isotope ions)
at m/z 75 are observed in all spectra and additionally confirm the
structure.
As an example, the EI MS spectrum of O,O-dibutyl 2-
chlorovinylarsonite 17 is presented in Figure 1. The spectrum shows
only a very weak peak of the M+· ion at m/z 282 (1%) as well as
a peak for the As(OBu)+2 ion at m/z 221 and the intense signal of
ClCH CH As O+Bu ion at m/z 209 (base ion). The ions As(OH)OBu+
at m/z 165, ClCH CH As O+H at m/z 153, ClCH CHAsH+ at m/+z
137, ClCH CHAs+· at m/z 136, ClAs O+H at m/z 127, HO As(OH)2
at m/z 109, AsC2H+ at m/z 101, as well as m/z 57 and 41 (n−butyl
group in the esters)2confirm the structure. An intense signal at m/z 71
(no chlorine atom) may correspond to a dihydrofuranylium ion C4H7O+
resulting from a rearrangement of the n−butoxy group.
The mass spectrum of the sulfur analogue is different. In the EI
MS spectrum of S, S−dibutyl 2-chlorovinylarsonodithiolite 18, the rel-
atively intense M+· ion at m/z 314 (12%) as well as [M-·Bu]+ at m/z 257
and [M-·SBu]+ at m/z 225 are present, together with the ions Cl As S+
Bu at m/z 199, ClCH CH As S+H at m/z 169, As S+Bu at m/z 164,
AsCl+ at m/z 110, As S+ at m/z 107, SBu+ at m/z 89, and As+ at
FIGURE 1 MS spectrum of O,O-dibutyl 2-chlorovinylarsodithiolite 17.

Reaction of Lweisite-1 with Alcohols, Diols, and Thiols
2317
FIGURE 2 MS spectrum of S, S-dibutyl 2-chlorovinylarsodithiolite 18.
m/z 75. The intense ions Bu+ at m/z 57 and [n-Bu - CH4]+ at m/z41,
typical for the n−butyl group, additionally confirm the structure. The
prominent ion at m/z 204 (no chlorine, 2 sulfur atoms) corresponds to
BuSCH CHSBu+·, resulting from a rearrangement (Figure 2).
The reactions of L1 with bifunctional alcohols and thiols were also
carried out. Since 5-membered cyclic arsonodithiolite derivatives of
Lewisite-1 with 1,2-ethanetiol 5 and 3,4-dimercaptotoluene7 are easy
to prepare,5,9−11 the analogous compounds were expected to form from
ethylene glycol (EG, 37) and 2-mercaptoethanol (2-ME, 38). Derivati-
zations were performed in water at 40◦C for 3 h at 10 ppm concen-
trations of compounds 37 and 38 and a large excess (200 ppm) of L-1
1. Cyclic derivatization products, appropriately 2-(2-chlorovinyl)-1,3,2-
dioxarsolane (L1=EG, 19) and 2-(2-chlorovinyl)-1,3,2-oxathiarsolane
(L1=2-ME, 20), have been smoothly obtained (Scheme 3).
The EI mass spectra of compounds 19 and 20 show distinguishable
to strong molecular ions at m/z 196 (8%) and 212 (43%), respectively.
The base peaks in the mass spectra, the dioxarsolylium ion at m/z 135
for L1=EG and the oxathiarsolylium ion at m/z 151 for L1=2-ME, in
SIM mode showed high abundance and excellent signal-to-noise (S/N)
ratio, thus derivatization with L1 is a method to easily detect diols
37 and 38 in water at least at a ppm level. Other ions present in the
spectrum of 19, [M - H2C=O]+· at m/z 166 and As O+ at m/z 91, and in
the spectrum of 20 [M - HC CH]+· at m/z 186 and As S+ at m/z 107,
as well as present in both spectra Cl CH=CHAs+· at m/z 136, AsCl+
at m/z 110, AsC2H+· at m/z 100 and As+ (m/z 75), additionally confirm
the structure of compounds 19 and 20.

2318
M. S. Sokolꢀowski and L. Konopski
SCHEME 3 Reactions of Lewisite-1 with bifunctional alcohols and thiols in
water at 40◦C.
Nonetheless, derivatization of bifunctional thiodiglycol TDG 9
showed to be much more interesting. Already after 2 h at 40◦C, TDG
present in water in a large concentration range from 100 ppb to 10000
ppm, in the presence of an excess (3 to 200 times) of Lewisite-1,
was unexpectedly easily transformed into an 8-membered cyclic ar-
sonite derivative, 2-(2-chlorovinyl)-1,3,6,2-dioxathiarsocane (L1=TDG,
21). The derivatization carried out at pH 6 and 2 gave similar results.
All forms of Lewisite-1—the dichloroarsine form 1, the arsonous acid
form L1(OH)2, the form 25 as well as the (L1-O)3 form 26a are suitable
to derivatize TDG in water. The reaction may be also performed with
the (L1-O)3 form 26a in dichloromethane. In the SIM mode, the base
ion in the MS of L1=TDG at m/z 195 showed a high selectivity (practi-
cally only one ion present in the SIM chromatogram) and an excellent

Reaction of Lweisite-1 with Alcohols, Diols, and Thiols
2319
SCHEME 4 EI MS fragmentation pathways of L1=TDG21.
S/N ratio, more than 1000 even at 100 ppb concentration range. In the
TIC mode, in a concentration of 1–10 ppm the L1=TDG 21 peak was a
prominent and easily to distinguish signal, even in very complex water
matrices.
The TDG and L1 derivatization product 21 showed to be a very sta-
ble compound. When the reaction time was extended up to 25 h, it was
still present in the sample in a high concentration. However, some side
reactions have been observed. Thus a 14-membered condensation prod-
uct of two molecules of TDG with L1, L1=(TDG)2 22 was observed in
the TIC at a higher retention time. The formation of macrocyclic rings
is favored by the high dilution during derivatization and by the pres-
ence of catalytic amounts of aprotic dipolar solvents, like DMSO, or
similar to DMSO thiodiglycol sulfoxide (TDGO, 31). Moreover, a con-
siderable amount of L1=TDG 21 degradation product, identical with
2-(2-chlorovinyl)-1,3,2-oxathiarsolane (L1=2-ME, 20) has been found
in the TIC (Figure 4).

2320
M. S. Sokolꢀowski and L. Konopski
In the EI MS of 2-(2-chlorovinyl)-1,3,6,2-dioxathiarsocane (L1=TDG)
21, the distinctly visible molecular ion at m/z 256 (3%) is present. The
fragmentation pathways are shown in the Scheme 4, and the mass
spectrum in Figure 3.
The EI MS spectrum of 2-(2-chlorovinyl)-1,3,9-trioxa-6,12-dithia-2-
arsacyclotetra-decane, L1=(TDG)2 22 (Figure 4) contains a weak sig-
nal for the molecular ion at m/z 360 and a prominent signal of the
[M - ClCH=CH·]+ ion at m/z 299. Other ions present in the spectrum,
[L1=TDG-H]+ at m/z 255 ([299]+ - ethylene oxide), m/z 239 ([299]+
-
ethylene sulfide), dioxathiarsocanylium ion C4H8AsO2S+ at m/z 195,
oxathiarsolylium ion C2H4AsOS+ at m/z 151, AsOCH2+· at m/z 105,
[ethylene sulfide]+· at m/z 60, [ethylene sulfide H·]+ at m/z 59 and
61, EtOH+· at m/z 46, [ethylene oxide + H·]+ at m/z 45, as well as
FIGURE 3 SIM chromatogram and MS of L1=TDG 21 (1 ppm TDG in water
derivatised with L1).

Reaction of Lweisite-1 with Alcohols, Diols, and Thiols
2321
FIGURE 4 TIC chromatogram and MS of L1=(TDG)2 22.
the previously discussed ions at m/z 136, 110, 107, 91, and 75 addi-
tionally confirm the structure of 14-membered heterocycle L1=(TDG)2
22.
The derivatization reaction may be also performed with equimolar
amounts of TDG and L1. However, it failed when TDG was present in
a large excess, possibly due to the tendency of this bifunctional alcohol
to polymerise. That is why the described method is a very simple and
efficient way to detect trace amounts of TDG in water using L1 as a
derivatization agent, rather then the opposite. The sample preparation
is very simple, and a tedious and time-consuming evaporation of water
and then silylation may be eliminated. Moreover, the detection limit
and the selectivity of the reaction are very good.
The reaction of L1 with a higher sulfur homologue of TDG, bis(2-
hydroxyethyl) disulfide 40, in water was also examined. After 3 h

2322
M. S. Sokolꢀowski and L. Konopski
at 40◦C, the disulfide 40 was smoothly transformed into the analo-
gous 9-membered cyclic arsonite derivative, 2-(2-chlorovinyl)-1,3,6,7,2-
dioxadithiarsonane 23.
The EI MS spectrum of the compound 23 contains the molecular
ion at m/z 288 (9%). The base ion, [M - ClCH CH·]+ at m/z 229 corre-
sponds to a dioxadithiarsonylium structure C4H8AsO2S+. The 1,3,4,2-
oxadithiarsinylium ion C2H4AsOS+ at m/z 183 (base 2ion—ethylene
2
oxide), and the previously discussed ions at m/z 212 and 151 are also
observed in the mass spectrum.
This method may be also used to derivatize diethylene glycol (DEG,
41), a TDG oxygen analogue, in water. 10 ppm DEG in water was easily
transformed after 3 h at 40◦C into an analogous 8-membered cyclic
arsonite derivative, 2-chlorovinyl-1,3,6,2-trioxarsocane (L1=DEG, 24,
Figure 5).
The EI MS spectrum of 2-chlorovinyl-1,3,6,2-trioxarsocane
(L1=DEG, 24, Figure 5) contains the weak molecular ion at m/z
240 (2%). The base ion [M - ClCH CH·]+ at m/z 179 gave high
abundance in both TIC and SIM modes with an excellent S/N ratio in
SIM mode. The trioxarsocanylium ion C4H8AsO+ at m/z 135 and the
3
other ions present in the spectrum: the previously mentioned ions at
m/z 136, 100, 91, and 75, as well as oxiranium ion C2H3O+· at m/z 43
additionally confirm the structure of compound 24.
The structures of all 5-, 8-, 9-, and 14-membered cyclic arsonite
derivatives discussed in this article were additionally confirmed by
chemical ionization mass spectrometry (CI MS, reagent gas: isobutane).
The MH+ quasi-molecular ions were found as base peaks (100%) in the
CI MS of the following compounds (m/z): 19 (197), 20 (213), 21 (257),
FIGURE 5 Mass spectrum of L1=DEG 23.

Reaction of Lweisite-1 with Alcohols, Diols, and Thiols
2323
23 (289), and 24 (241). In the CI MS spectrum of the 14-membered
cyclic compound 22 the signal for the MH+ ion at m/z 361 was of lower
intensity (15%).
Nevertheless, the attempts to derivatise bis(2-chloroethyl) sulfox-
ide (thiodiglycol sulfoxide, TDGO 39), another environmental oxida-
tion product of a sulfur mustard, unexpectedly failed. Even 400–
600 ppm water solutions of TDGO did not produce any deriva-
tive with L1. This may be due to the different geometry and high
1
polarity10 of the TDGO molecule (see Scheme 3). The H NMR spec-
trum shows that the molecule is asymmetrical.22 Maybe also a redox
reaction takes place, and the resulting As(V) analogue of Lewisite-1, 2-
chlorovinyldichloroarsine oxide 42 does not form derivatives with TDG
also due to a different molecule geometry. Our experience showed as
well, that As(V) organic compounds, such as cacodylic acid Me2As(O)OH
43, did not form any esters with alcohols and diols in water.23
The RIs of the cyclic 2-chlorovinylarsonous acid esters obtained are
shown in Table II.
All Lewisite derivatives discussed in this article showed in TIC usu-
ally two or sometimes more peaks. This was due to geometrical iso-
merism of the Lewisite molecule. According to NMR data, the highest
peak corresponded to (E)-2-chlorovinyl isomer, (E)-Cl–CH=CH–AsCl2,
(J = 15 Hz), whereas the smaller peaks corresponded mainly to (Z)-
HH
isomer (J = 8 Hz). This is in contrast to some literature data, where
HH
the (E) and gem (CH2 =CHCl–AsCl2,
J
= 1 Hz) isomers are mainly
HH
expected in the Lewisite molecules, whereas the (Z)-2-chlorovinyl iso-
mer, (Z)-ClCH=CH–AsCl2, is practically absent.24 However, the mass
spectra of the isomers of the compounds discussed in this article did not
show any significant differences.
CONCLUSIONS
The method described above may be used not only to derivatize
Lewisite-1 in water with alcohols (and especially thiols), but also to
derivatize some alcohols, particularly diols—such as thiodiglycol 9—
with Lewisite in water matrices at 100 ppb levels, alternatively to time-
consuming evaporation and silylation. This simple novel method has
been successfully applied to the analysis of CWC related environmen-
tal water samples.
The stable derivatives resulting from the reaction of TGD 9 and
bis(2-hydroxyethyl) disulfide 40 with Lewisite-1 contain 8-, 9-, and 14-
membered rings of arsenic, oxygen and sulfur atoms and are new types
of heterocyclic compounds, not described before in the literature.

2324
M. S. Sokolꢀowski and L. Konopski
EXPERIMENTAL
Materials
2-Chlorovinyldichloroarsine 1 (Lewisite-1), 5 mg/mL solution in wa-
ter, was obtained from Spiez Laboratories, Spiez, Switzerland. Bis(2-
hydroxyethyl) sulfide 9 (for chromatography, International Enzymes
Ltd.), methanol 31 (spectrometric grade, Aldrich, 99.9%), ethanol32
(analytical grade, Baker >99.8%), propanol 33 (analytical grade, Baker
>99%), isopropanol 34 (analytical grade, Baker >99%), butanol 35
(Aldrich, 99%), 1-butanethiol 36 (Aldrich, >99%), ethylene glycol 37
(Aldrich, >99%), 2-mercaptoethanol 38 (Aldrich, 98%), thiodiglycol sul-
foxide 39 (Radian, 99%), bis(2-hydroxyethyl) disulfide 40 (Aldrich, tech.
grade), diethylene glycol 41 (Aldrich, 99%), dichloromethane (analyti-
cal grade, Baker, 99.9%), acetone (analytical grade, Baker, 99.5%), hy-
drochloric acid 0.1 M (analytical grade, Boom), and anhydrous sodium
sulfate (Fluka, >99%) were used.
Water matrix: demineralized or tap water.
Equipment
GC/MS Conditions
HP 6890 Series gas chromatograph was coupled on-line with a HP
5792A Mass Selective Detector (MSD).
GC/MS analysis was performed on Hewlett-Packard, HP 6890 GC
/5972A MSD. The instrument conditions used were as follows:
GC conditions. FSOT capillary column, 30 m × 0.25 mm I.D., phase:
5-HP MS (95% dimethylsiloxane, 5% phenylsiloxane), film 0.25 μm,
carrier gas: helium, constant flow 0.9 ml/min; injection: split/splitless
(splitless mode with 1 min splitless period), injection volume 1-2 μl
(manually), injector temperature: 250◦C. Column temperature: 40◦C (2
min) then increased to 280◦C (10◦C/min) and at 280◦C (4 min).
Mass spectrometry conditions. Electron ionization (EI) at 70 eV, ion
source temperature 180◦C, trap current 200 μA, accelerating voltage
1870 V, analyzator: quadrupole. Resolution 0.7 u, mass range 40 to 550
u. The chromatograms were performed in both Total Ion Current (TIC)
or Selected Ions Monitoring (SIM) modes. Chemical Ionization (CI):
reagent gas: isobutane.
GC/FID/FPD Conditions
HP 6890 Series gas chromatograph equipped with an autosampler
and, in parallel, Flame Ionization Detector (FID) and Flame Photomet-
ric Detector (FPD), optical filter wavelength for sulfur: 394 nm. CG
conditions: the same as for GC/MS.

Reaction of Lweisite-1 with Alcohols, Diols, and Thiols
2325
Sample Preparation
Derivatization and Sample Preparation—General Procedure
To 1 mL of the water solution of an appropriate alcohol, hydroxythiol
or diol 31–35, 37–41 in a 4-mL vial with PTFE-lined screw-cap, the 5
mg/mL water solution of Lewisite-1 1 was added in such amounts that
the content of the alcohol/hydroxy thiol/diol in solution was in the range
100 ppb (ng/g)–10,000 ppm (μg/g), usually 1–10 ppm, and Lewisite was
in molar excess of 1 to 200 times (usually 3 to 6 times). Reaction was
usually carried out at pH 6; if the reaction was performed at pH 2, the
appropriate amount of 0.1 M aqueous hydrochloric acid was added. The
cap was then screwed on and derivatization was carried out at 40◦C for
2–25 h, usually 3 h. After cooling, the water matrix was washed with
dichloromethane (3 × 1 mL), the combined organic layers were dried
with anhydrous sodium sulfate for 30 min and filtered. Depending on
the concentration of the alcohol, samples were concentrated (fivefold)
or not, in a mild nitrogen flow at room temperature (usually, at 1–10
ppm concentration, no evaporation was necessary).
One to two μL of the resulting dichloromethane solution was injected
in GC/MS or GC/FID/FPD. Linear (van den Dool) retention indices (RI)
were calculated by a linear polygon method25 with retention times (RT)
of even carbon number hydrocarbons from C8 (octane) to C24 (tetrade-
cane), 10 μg/mL each, injected under the same conditions in the GC/MS.
All discussed spectra fragmentations were confirmed by calculating
the intensity of the isotope peaks of the fragment ions.
Derivatization of Thiodiglycol 9 with Lewisite-1 1 in Water
To 1 mL of water containing 10 μg of thiodiglycol 9 (10 ppm) in a 4-mL
vial with PTFE-lined screw-cap, 20 μL of water solution of Lewisite-
1 1 (5 mg/mL, molar excess 5.9 times) was added. The cap was then
screwed on and derivatization was carried out at 40◦C for 2 h. After
cooling, the mixture was washed with dichloromethane (3 × 1 mL), the
combined organic layers were dried with anhydrous sodium sulfate for
30 min and filtered. one μL of the resulting dichloromethane solution
was injected in the GC/MS. In the above described conditions, the RT of
2-chlorovinyl-1,3,6,2-dioxathiarsocane 21 was 17.77 min.
Derivatization of Thiodiglycol 9
(i) With Water Solution of 2-Chlorovinylarsonous Acid L1(OH)2
25. One mL of Lewisite-1 in water (5 mg/mL) were washed with
dichloromethane (3 × 1 mL). To the water phase, containing mainly 2-
chlorovinylarsonous acid 25, was added 1 mL of water containing 2 ppm
of thiodiglycol 9 and derivatization was performed in a 4-mL screw-cap

2326
M. S. Sokolꢀowski and L. Konopski
vial at 40◦C for 2 h. After cooling, the water matrix was worked out
as described in general procedure. Two μL of the organic solution was
directly injected in the GC/MS and GC/FID/FPD. RT of compound 21
was as above.
(ii) With Lewisite-1 Oxide Trimer (L1-O)3 26a in Dichloromethane.
Three hundred μL of the above combined organic layers, containing
mainly (L1-O)3 26a, was shaken with 1 mL of water solution of TDG (1
ppm, 1 μg) in a 4-mL screw-cap vial. The reaction mixture was kept at
40◦C for 2 h, shaking occasionally. After cooling, the reaction mixture
was worked out as described in general procedure. Two μL of the organic
solution was directly injected in the GC/MS and GC/FID/FPD. RT of
compound 21 was as above.
(iii) Synthesis of Compound 21 from (L1 − O)3 26a and TDG 9 in
Dichloromethane. Three mL of Lewisite-1 in water (5 mg/mL, contain-
ing 15 mg (72 μmol) of Lewisite-1) was washed with dichloromethane (1
× 2 + 3 × 1 mL). The combined organic extracts were dried (Na2SO4),
filtered, and then added to 5.16 mg (42 μmol) of thiodiglycol 9 in a 4-
mL vial equipped with a PTFE-lined screw-cap. The reaction mixture
was kept at 40◦C for 3 h, cooled, and the unreacted TDG was washed
out with water (3 × 2 mL). The organic phase was dried (Na2SO4), fil-
tered and evaporated to dryness in a mild stream of nitrogen at room
temperature. Uncolored oil, yielded 5.3 mg (49%).
EI and CI GC/MS: see discussion.
1H NMR (500 MHz, CDCl3, δ [ppm]): 2.63 (ddd, 2H, H-5, H-7); 2.98
(ddd, 2H, H-5, H-7); 4.02 (ddd, 2H, H-4, H-8); 4.37 (ddd, 2H, H-4, H-
8); 6.56 (d, J = 15 Hz, 1H, H-1), 6.65 (d, J = 15 Hz, 1H, H-2);
HH
HH
(configuration E−).
13C NMR (DEPT 90◦, 125.7 MHz, CDCl3, δ [ppm]): 29.7 (C-5, C-7),
68.3 (C-4, C-8).
Derivatization of 2-Chlorovinylarsonous Acid 25 with
1-Butanethiol 36 in Water
1 mL of Lewisite-1 in water (5 mg/mL) was washed with
dichloromethane (3 × 1 mL). To the water phase, containing mainly
2-chlorovinylarsonous acid 25, solution of 1-butanethiol 36 in acetone
(5 mg/mL, 100 μL) was added. After 10 min at room temperature, the
reaction mixture was worked out as described in the general procedure.
One μL of the organic solution was directly injected in the GC/MS and
GC/FID/FPD. Under the conditions described above RT of S, S−dibutyl
2-chlorovinylarsonodithiolite 18 was 20.74 min.

Reaction of Lweisite-1 with Alcohols, Diols, and Thiols
2327
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