Degradation of Sulfur Mustard on KF/Al2O3: The Role of Organic Solvents and Active Species

Article abstract of DOI:10.1021/acs.joc.8b01314

Solvent effects on the ability of KF/Al₂O₃ supports to degrade the warfare agent sulfur mustard (HD) were explored. RP-KF/Al₂O₃ possessing hydroxide ions and ECUF/KF/Al₂O₃ holding fluoride

Full text of DOI:10.1021/acs.joc.8b01314

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Note
Degradation of Sulfur Mustard (HD) on KF/Al2O3:
The role of Organic Solvents and Active Species
Gil Fridkin, Ishay Columbus, Lea Yehezkel, and Yossi Zafrani
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01314 • Publication Date (Web): 13 Jul 2018
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Degradation of Sulfur Mustard (HD) on KF/Al O : The role of Organic
2
3
Solvents and Active Species
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Gil Fridkin,* Ishay Columbus, Lea Yehezkel and Yossi Zafrani*
Department of Organic Chemistry, Israel Institute for Biological Research,
Ness-Ziona 74100, Israel
gilf@iibr.gov.il ; yossiz@iibr.gov.il
Abstract
Solvent effects on the ability of KF/Al O supports to degrade the warfare agent sulfur
2
3
mustard (HD) were explored. RPꢀKF/Al
2
O
3
possessing hydroxide ions and ECUF/KF/Al
containing 10 wt % of
. Additionally, RPꢀKF/Al led
to elimination products while ECUF/KF/Al O mainly to substitution derivatives. Enlarging
2 3
O
holding fluoride ions, were examined. Reactions on RPꢀKF/Al
organic solvents were faster than those on ECUF/KF/Al
2 3
O
2
O
3
2 3
O
2
3
the solvent amounts to 90 wt % resulted in decreased reaction rates. The significance of
solvent identity/amount and active species are discussed.
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Development of effective methods for decontamination of chemical warfare agents
1
ꢀ4
(
CWAs) applied in both military and homeland scenarios is most relevant as evident from
5
recent events of CWAs use. Among the array of approaches available for that purpose,
reactive sorbents that physically adsorb and chemically degrade CWAs to nontoxic products
seems to hold great potential. Indeed, in recent years an extensive effort has been directed
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7ꢀ10
11
towards the study of various active supports, such as nanosized MgO, Al
2
O
3
,
CaO,
12
13ꢀ15
16ꢀ18
Zr(OH)4, and TiO2,
as well as metal organic frameworks (MOFs)
that have
capabilities to decontaminate CWAs. Acknowledging the attractiveness of this approach we
were recently engaged with the examination of the potential of various impregnated alumina
supports, i.e. RPꢀKF/Al
Coordinatively Unsaturated Fluoride)
decontaminate CWAs. Indeed, we have found that the extremely toxic organoꢀphosphorus
OP) based CWAs VX (Oꢀethyl Sꢀ2ꢀ(diisopropylamino)ethyl methylphosphonothioate) and
2
O
3
(regular preparation), ECUF/KF/Al
2
O
3
(Enriched with
19,20
21
4 2 3,
and R NF/Al O
to actively and effectively
(
GB (Oꢀisopropyl methylphosphonofluoridate, sarin) as well as the blister agent sulfur
mustard (2,2'ꢀdichloroethyl sulfide, HD) were effectively degraded on these supports with
1
9ꢀ21
reaction halfꢀlife times ranging from few minutes to several hours.
Typically, small
amount of water was added to the supports in these studies to achieve these results, while
with the dry powders extremely long reaction times were obtained. However, in respect of
potential application of these types of powders in the field, we envisioned that further
addition of an organic solvent will be required to promote facile and effective dispersal of the
sorbent as well as rapid diffusion of the CWAs towards the powder active sites. Accordingly,
we have recently explored the effects organic solvents have on the fluorideꢀpromoted
2
2
heterogeneous hydrolysis and alcoholysis of various OP compounds, among them the CWA
23
VX, on the surface of ECUF/KF/Al
2
O
3
. These experiments showed that not only is the
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identity of the solvent important in these reactions but also its quantity. It was proposed that
addition of minute quantity (3ꢀ10 wt %) of the proper solvents is suffice to permit mobility of
the reaction components while maintaining their very high local concentration in close
proximity to the solidꢀsupport large porous surface area. Under these conditions, acceleration
of reactions rates by order of magnitudes was obtained. Most importantly, leaching of
fluoride ions, which were found pivotal in the mechanism of OP's hydrolysis/alcoholysis, was
prevented in such small amounts of solvents.
1
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In order to develop a universal decontamination sorbent, namely, one that will effectively
detoxify OP CWA's as well as HD type of agents, it was of interest for us to complete and
examine whether the above notions on solvents effects could also be implemented for the
effective decontamination of the more hydrophobic agent HD on such matrices. To the best
of our knowledge, solvent effects on HD decontamination reactions on solidꢀsupports were
not explored before. A study on the reactions of an HD simulant, 2ꢀchloroethylethyl sulfide
(2ꢀCEES), in the presence of MgO (~150 mg) and large amounts (10 mL) of pentane,
24
methanol and THF was however reported. Using GCꢀMS as their method of analysis, the
authors showed that surprisingly the most hydrophobic and inert solvent pentane led to the
fastest reactions. Accordingly, we envisioned that degradation studies of HD itself on KF
impregnated alumina supports wetted with different amounts (minute to large) of organic
solvents and monitored by NMR would provide significant information. The results of these
studies are described herein with specific attention to products identity and volume of
solvents used.
For this study, methanol and ethanol were chosen as representatives of polar protic solvents,
acetonitrile as an example of a polar aprotic solvent and heptane as a hydrophobic solvent.
On the basis of previous kinetic data, we have decided to perform the solvent effect study on
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2 3
HD decontamination with two of our leading supports, namely, RPꢀKF/Al O and
19ꢀ21
2 3
ECUF/KF/Al O (Table 1).
Table 1. Kinetics and product distribution of HD degradation reactions
a
2 3 2 3
on RP-KF/Al O and ECUF/ KF/Al O in the presence of solvents.
d
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Elimination vs
e,f,g
Sol.
Substitution
Run
Solid support
Sol.
%
t
1/2 (h)
Products(%)
b
e
1
2
3
4
5
6
7
8
9
RPꢀKF/Al
ECUF/KF/Al
RPꢀKF/Al
ECUF/KF/Al
2
O
3
ꢀ
ꢀ
ꢀ
ꢀ
355
319
138
224
80
23
18
19
97
3
20
77
82
81
b
e
e
e
2
O
3
b
2
O
3
Water
Water
MeOH
MeOH
MeOH
MeOH
EtOH
EtOH
Hep
Hep
Hep
MeCN
MeCN
10
10
10
90
100
10
10
10
10
90
10
10
10
b
2
O
3
c
f
RPꢀKF/Al
RPꢀKF/Al
None
2
O
O
3
18.5
3
c
f
2
3
102
347
97
c
f
0
100
c
f
ECUF/KF/Al
RPꢀKF/Al
ECUF/KF/Al
2
O
3
30.1
21.1
578
42.0
105
996
91
93
39
93
93
81
95
14
9
7
61
7
7
19
5
86
c
g
2
O
3
c
e,g
1
1
1
1
0
1
2
3
2
O
3
c
e
RPꢀKF/Al
RPꢀKF/Al
2
O
O
3
c
e
2
3
c
e
e
ECUF/KF/Al
RPꢀKF/Al
ECUF/KF/Al
2
O
3
c
e
14
2
O
3
50.6
c
15
2
O
3
1751
a
b
Products ratio at the end of the reactions. On the basis of our previous
Loading of 5% HD. CEVS (1), DVS
3), traces of HOEVS (2). TDG (4), TDG oligomers (5), Thioxane (6).
methoxyethyl chloroethylsulfide (7), bis(2ꢀmethoxyethyl)sulfide (8).
ethoxyethyl chloroethylsulfide (9), bis(2ꢀethoxyethyl)sulfide (10).
2
0
c
d
study, loading of 6.5% of HD.
e
f
(
g
Although prepared from the same materials, i.e. alumina and KF, due to variation in their
protocol of preparation these supports differ in the nature of their active species. Specifically,
in the case of RPꢀKF/Al
2
O
3
which is prepared in water, the fluoride ions are mainly
AlF and the support active species
, which is prepared in methanol or
ethanol, the fluoride ions are "free" and available for reactions, as the formation of K AlF is
consumed for the formation of inactive waterꢀinsoluble K
3
6
25
2 3
are hydroxide ions. In the case of ECUF/KF/Al O
3
6
19ꢀ21
prevented in these solvents (eq. 1ꢀ2).
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This difference was previously shown to have marked effect on the kinetics of OP CWAs
decontamination reactions on these dry or water wetted matrices, i.e. reactions on
ECUF/KF/Al
2 3 2 3
O were found to be much faster and effective than those on RPꢀKF/Al O ,
presumably due to the major role the fluoride ion has in the hydrolysis mechanism of
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9,26
OPs.
) on these matrices in the presence of 10 wt % of organic solvents, however in an opposite
direction. Namely, RPꢀKF/Al appears superior than ECUF/KF/Al for these reactions
As can be seen in table 1, this pattern also exists in the case of HD reactions (5 wt
%
2
O
3
2 3
O
in all solvents. In the case of ethanol, heptane and acetonitrile this behavior is most
pronounced with degradation reactions up to ~20ꢀ30 times faster on RPꢀKF/Al O than on
2
3
ECUF/KF/Al O (runs 9, 11, and 14 versus 10, 13 and 15 respectively). In the case of
2
3
methanol, however, the reaction on the former was only ~1.5 times faster than that on the
latter (run 5 versus 8). Interestingly, reactions on RPꢀKF/Al in the presence of all organic
2
O
3
solvent examined resulted in improved kinetics as compared to reactions on the dry or water
wetted supports. For example, reaction in the presence of 10 wt % methanol (run 5) was
found to be ~7 times faster than that in the presence of 10 wt % of water (run 3). However, in
2 3
the case of ECUF/KF/Al O , only methanol (run 8) led to a faster reaction, ~ 7 times, than
that obtained in the presence of water (run 4). All other solvents led to extremely slow
transformation rates, even much slower than that observed on the dry support. Apart of the
different kinetics, the reactions on the two supports differed also in the identity of the
2
7
products obtained as well as their ratio (Table 1). It should be noted that hydrolysis or
elimination pathways are favored over oxidation for this environmentally persistent and
28
hydrophobic CWA, as some of its oxidation products are toxic. Reactions on RPꢀKF/Al
2
O
3
in the presence of all solvents led almost exclusively (93ꢀ97%) to the elimination products, 2ꢀ
chloroethyl vinyl sulfide (CEVS, 1) and divinyl sulfide (DVS, 3), while only small amount
(3ꢀ7%) of substitution products were observed (Scheme 1 and Figure 1). However, on
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ECUF/KF/Al
2
O
3
t
he product identity and distribution varied contingent on the solvent used.
In the case of methanol and heptane, elimination products were mostly obtained, while in the
case of ethanol and acetonitrile substitution products were predominant. Significantly, all
28
products obtained in these experiments are relatively of nonꢀtoxic nature.
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Scheme 1. Optional HD degradation products on KF alumina supports.
HD
t = 0.2 h
t = 5.7 h
t = 23.0 h
CEVS
t = 71.2 h
CEVS
t = 170 h
DVS
140
130
120
110
100
90
80
70
60
50
40
30
20
10 ppm
1
3
Figure 1. Selected CꢀNMR spectra of HD degradation reactions on RPꢀ
KF/Al in the presence of 10 wt % of methanol. See scheme 1 for
structures.
2
O
3
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In order to understand the above results, the solubility/mobility of HD in the organic solvents
and the relative activity of the powders active species towards this substrate should be
considered. Although only minute amounts, i.e. 10 wt %, of solvents were added, such that
the supports maintained their solid nature, this volume is in principal suffice, as we recently
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
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3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
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5
5
5
5
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5
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0
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2
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0
22,23
showed for the degradation of OPꢀbased CWA and simulants,
to afford effective mobility
of all reaction components. Since in a specific solvent HD is mobile on the two supports to
the same extent, the different reactions kinetics obtained on them must arise from the fact that
KOH is a stronger base than KF. Accordingly, it probably better activates the RPꢀKF/Al
2 3
O
support towards reaction with HD and makes it superior than ECUF/KF/Al O , although the
2
3
20
surface area of the former matrix is lower than the latter. The different kinetics obtained on
a specific support in the presence of the various solvents may stem from the different
solubility of HD as well as of the active species KOH or KF in them. Interestingly, in the case
of RPꢀKF/Al
solvents (although different in nature) led to similar kinetics with t1/2 times ranging from
8.5h to 50.6h. Specifically, due to the rather high solubility of KOH in methanol and ethanol
2 3
O these differences somewhat compensated each other such that all four
1
(
Table S1 in the supporting information) these solvents led to 2ꢀ3 times faster reaction rates
runs 5 and 9) than those obtained in heptane and acetonitrile (runs 11 and 14). The latter
(
solvents managed to mediate relatively fast reactions, albeit the negligible solubility of KOH
in them, due to their ability to promote effective diffusion of HD to the support active pores.
In the case of ECUF/KF/Al O experiments, however, a large difference in reaction times
2
3
was obtained (~30 to 1750h) among these solvents. The substantial reactions rate difference
between the two polar protic solvents methanol and ethanol (runs 8 and 10) stems from the
large difference of KF solubility's in these solvents (MeOHꢀ 10.3g/100g solvent, EtOHꢀ
0.1g/100g solvent, see Table S1 in the supporting information). A similar reaction rate
difference phenomena in the presence of these solvents was also observed by us in the case of
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2
an organoꢀphosphorous compound. Heptane and acetonitrile which negligibly solubilize KF
mediated even much slower reactions than ethanol (runs 13 and 15). In respect to the
products obtained and their ratio, the activity of KOH and KF in elimination or substitution
reactions should be examined. Evidently, once strong bases like KOH are present on the
support and are accessible in the presence of organic solvents, elimination reactions are
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favored over substitution. For example, in the RPꢀKF/Al O experiments the elimination
products CEVS (1) and DVS (3) were almost the sole products obtained while substitution
products were obtained only in trace amounts. Since KF is a weaker base than KOH and in
addition it exhibits lower solubility in the examined solvents (Table S1 in the supporting
29ꢀ33
information),
reactions on ECUF/KF/Al O apart of slower kinetics typically provided a
2 3
much more complex mixture of products. In general, as longer the reactions became, the ratio
between elimination and substitution products shifted towards the latter. Apparently,
elimination reactions of HD are quicker, however, if not occurring, slow hydrolysis promoted
by surface hydroxyl group or residual amounts of water present in the solvents is obtained.
In order to evaluate the effect large amounts of solvents promote, experiments in the presence
2 3
of 90 wt % of solvents were next performed. Specifically, RPꢀKF/Al O was mixed with 90
wt % of methanol or heptane holding 5 wt % of HD, and the mixtures were examined
periodically, after vigorous shaking, using solution NMR. The results showed that enlarging
the solvent amounts led to decreased reactions rates, i.e. ~5 times for methanol (run 6) and
~
2.5 times for heptane (run 12), as compared to reactions in the presence of 10 wt % of
solvents (runs 5 and 11). Most interestingly was the fact that the increased amount of
methanol led solely to the methanolꢀbased substitution products methoxyethyl
34
chloroethylsulfide (7) and bis (2ꢀmethoxyethyl)sulfide (8), while in the presence of 10 wt %
of methanol elimination products were predominantly obtained (Figure S2 in the Supporting
Information). Evidently, the relatively large amount of methanol afforded effective leaching
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of both KOH and HD from the KF/Al O support, such that the decontamination reactions
practically occurred in the solution phase in the presence of active methoxide ions. The fact
that the pH of the solution at the end of the experiment was found to be 11 further supports
this notion. Under heterogeneous conditions, i.e. once a minute amount of solvent is added,
KOH leaching is prevented and elimination reactions of HD, which probably forms specific
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interactions with the RPꢀKF/Al
To further substantiate that the reactions in the presence of 90 wt % of methanol occurs
mainly due to KOH leaching from the RPꢀKF/Al support and not only from methanol
2 3
O support, are promoted on the basic solid media.
2
O
3
intrinsic nucleophilic activity, a control solvolysis experiment in which only methanol and
HD were mixed, was performed. Indeed, it was found, that although not inert, methanol itself
led to a solvolysis reaction ~3 times slower (run 7) than that obtained in the presence of 10 wt
%
of the powder (run 6). In the case of heptane, since KOH has negligible solubility in it,
even large amount of this hydrophobic solvent did not mediate leaching of the salt, as was
also evident from the neutral pH the solution exhibited at the end of the experiment. In
accord, reactions of HD must have occurred only after its diffusion and adsorption to the
2 3
RP/KF/Al O matrix. Once adsorbed, the support mediated the formation of the elimination
product CEVS (1) which was also the major product obtained under heterogeneous
conditions in the presence of 10 wt % of solvent.
Solvent effects on the degradation reactions of HD were explored. Our results demonstrated
that organic solvent wetted supports mediated much quicker reactions than those obtained on
the dry or water wetted matrices, seemingly due to the improved diffusion HD exhibits under
these conditions. Reactions of HD on RPꢀKF/Al
2
O
3
were found to be much faster than those
activity
on ECUF/KF/Al . It seems reasonable to assume that the increased RPꢀKF/Al O
2
O
3
2 3
is derived from hydroxide ion being a stronger base than fluoride ion. Small amounts of
solvents were found beneficial for such reactions as leaching of active species was avoided
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while effective mobility of the reaction components and high concentration reactions were
still maintained. Usage of small amounts of solvent is of course also mostly desired from
environmental and economical considerations. We believe, that the fact that this pattern was
observed in our studies might suggest that using minute amounts of the appropriate solvent is
advantageous in general.
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Experimental section
Caution: These experiments should only be performed by trained personnel using applicable
safety procedures.
1
3
Materials and chemicals. HD labeled with C (HD*) was prepared (>99% purity)
35
13
according to a literature procedure. The C label was distributed evenly among the carbons.
KF (≥99%), Al (activated, neutral, 150 mesh 58Å), Methanol (HPLC grade), Heptane
HPLC grade) and acetonitrile (HPLC grade) were purchased from commercial suppliers.
Deionized water was obtained from a laboratory water purification system. RPꢀKF/Al
(regular preparation) and ECUF/KF/Al O (Enriched with Coordinatively Unsaturated
2 3
O
(
2
O
3
2
3
20,23
Fluoride) powders were prepared as previously described.
Preparation of powders wetted with 10% solvent: Dry powders (0.45 g) were placed in
glass vials and solvents (0.05 g) were added on top. The mixtures were vortexed and ground
thoroughly, using a glass rod, until homogenous powders were obtained (typically two or
three cycles).
Preparation of powder wetted with 90% solvent: dry powder, 0.03g, were placed in Teflon
NMR tubes, and 0.27 g of solvent (which contained 1.2 µl of HD) was added.
Sample preparation. Samples of the appropriate powders (40 mg) were added to the 0.4 cm
ZrO rotor and 1.6 µL HD, 5 wt %, were applied via syringe to the center of the sample. The
2
rotor was then sealed with a fitted KelꢀF cap. For the 90 wt %: 1.2 µl of HD was added to the
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solvent as described above. For the 100 % methanol (control experiment): 1.2 µl of HD was
added to 340 µL of methanol and the mixture was placed in a Teflon NMR tube.
13
Kinetic studies using MAS NMR: To obtain clear NMR data, Cꢀlabeled HD (HD*) was
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used. C spectra were obtained at 125 MHz on a 11.7 T (500 MHz) spectrometer, equipped
with a 0.4 cm standard CPꢀMAS probe, using direct polarization (i.e., no cross polarization
13
(
CP) was used). Typical spinning rates were 5 kHz. Chemical shifts for C were referenced
to external TMS as 0.0 ppm. The number of transients per spectrum varied between 100 and
2000. For comparison purposes, spectra were recorded under identical conditions. Spectra
were measured periodically to determine remaining starting material and identify degradation
products. In all cases, the reactions profiles fitted a pseudoꢀfirstꢀorder seemingly due to the
large excess of hydroxide or fluoride ions and a rateꢀdetermining step, such as diffusion of
the reactants.
Supporting Information
NMR spectra and kinetic profiles of all reactions. The supporting information is available
free of charge on the ACS Publications website at DOI.
Corresponding Authors
Eꢀmail: gilf@iibr.gov.il ; yossiz@iibr.gov.il
*
Tel.: +972 8 9381740. Fax: +972 8 9381548.
Notes
The authors declare no competing financial interest.
Acknowledgments
This work was internally funded by the Israeli Prime Minister's office.
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4. Products 7 and 8 were identified by NMR (Figure S2 in the supporting information),
albeit the methyl ether peak originating from methanol was not conclusively
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observed, as the methanol was not C labeled. Product's 8 identity was further
+
verified using GCꢀMS, (M+H) , 152.
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5. Reiff, L. P.; Taber, D. F.; Yet, L. Proceeding of the 1996 ERDEC Scientific
Conference on Chemical and Biological Defense Research, 19-22 November, 1996. P.
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