The autoxidation of triaryl trithioarsenites, (ArS)3As: Evidence for binding and activation of triplet dioxygen by arsenic(III)

Article abstract of DOI:10.1080/104265091000589

Triaryl trithioarsenites, (ArS)₃As, are oxidized by air to As₂O₃ and ArSSAr. In two cases the parent "thiol" (pyrid-2-thione and 1-hydroxypyrid-2-thione) is coproduced. The oxidation, in nonprotic solvents, is favored by electron-withdrawing groups at the para position of the phenyl group. The products obtained in nonprotic solvents were rationalized by assuming that the binding of the triplet dioxygen to arsenic(III) gives a triplet diradical, (ArS)₃As-O-O, or an arsenadioxirane, (ArS)₃As(O₂), intermediate, which decomposes after nucleophilic attack by another (ArS)₃As molecule. In protic solvents a zwitterion, (ArS)₃As⁺-O-O^-, and in the presence of moisture a hydroperoxy arsenic(V) compound, (ArS) ₃As(OH)-O-OH, may be intermediates in the air oxidation of some aromatic trithioarsenites. These data tend to indicate that arsenic(III) bound to suitable groups can directly bind dioxygen, a property which may have implications in chemotherapy and carcinogenesis. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/104265091000589

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The Autoxidation of Triaryl
Trithioarsenites, (ArS)3As:
Evidence for Binding and
Activation of Triplet Dioxygen
by Arsenic(III)
Maria N. Haikou a & Panayiotis V. Ioannou a
a Department of Chemistry , University of Patras ,
Patras, Greece
Published online: 16 Aug 2006.
To cite this article: Maria N. Haikou & Panayiotis V. Ioannou (2006) The Autoxidation
of Triaryl Trithioarsenites, (ArS)3As: Evidence for Binding and Activation of Triplet
Dioxygen by Arsenic(III), Phosphorus, Sulfur, and Silicon and the Related Elements,
181:2, 363-376, DOI: 10.1080/104265091000589
To link to this article: http://dx.doi.org/10.1080/104265091000589
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Phosphorus, Sulfur, and Silicon, 181:363–376, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265091000589
The Autoxidation of Triaryl Trithioarsenites, (ArS)3As:
Evidence for Binding and Activation of Triplet Dioxygen
by Arsenic(III)
Maria N. Haikou
Panayiotis V. Ioannou
Department of Chemistry, University of Patras, Patras, Greece
Triaryl trithioarsenites, (ArS) As, are oxidized by air to As O and ArSSAr. In
3
2 3
two cases the parent “thiol” (pyrid-2-thione and 1-hydroxypyrid-2-thione) is copro-
duced. The oxidation, in nonprotic solvents, is favored by electron-withdrawing
groups at the para position of the phenyl group. The products obtained in nonpro-
tic solvents were rationalized by assuming that the binding of the triplet dioxygen
˙
to arsenic(III) gives a triplet diradical, (ArS) As˙
O
O, or an arsenadioxirane,
3
(ArS) As(O ), intermediate, which decomposes after nucleophilic attack by another
3
2
(ArS) As molecule. In protic solvents a zwitterion, (ArS) As+
O
O−, and in the
3
3
presence of moisture a hydroperoxy arsenic(V) compound, (ArS) As(OH) OH,
O
3
may be intermediates in the air oxidation of some aromatic trithioarsenites. These
data tend to indicate that arsenic(III) bound to suitable groups can directly bind
dioxygen, a property which may have implications in chemotherapy and carcino-
genesis.
Keywords Activation; binding; dioxygen; triaryl trithioarsenites
INTRODUCTION
Evidence begins to accumulate indicating that arsenic(III) coordinated
to suitable organic groups can directly combine with dioxygen to give
unstable adducts that decompose to various products depending on the
nature of the organic groups. Thus, ascorbic acid complexed with arse-
nous acid, H3AsO3, in a ratio of 1:2 As(III)/ascorbic acid is oxidized by
air to dehydroascorbic acid much faster than in the absence of As(III).1
The reaction of allyl and benzylarsonic acids with thiophenol gave
not only the expected diphenyl alkyldithioarsonites, R As(SPh)2, and
diphenyl disulfide, PhSSPh, but also various other products, some of
which (As2O3, (PhS)3As, PhCH2OH, PhCH O) arose from the reaction
Received February 3, 2004; accepted February 10, 2005.
Address correspondence to Panayiotis V. Ioannou, University of Patras, Department
of Chemistry, Patras, Greece. E-mail: ioannou@chemistry.upatras.gr
363

364
M. N. Haikou and P. V. Ioannou
of these alkyldithioarsonites with the dissolved dioxygen.2 Attempted
oxidation3 of the esters 1–3, 5, 7, and 8 (without exclusion of air) by oc-
tasulfur in refluxing solvent, as melts, or in solution in the presence of
triethylamine, as an activator of octasulfur, did not give the expected
arsenic(V) esters, (ArS)3As S, but various amounts of As2O3 and disul-
fides, ArSSAr, (in the case of 8, the parent thiol, 2-mercaptopyridine,
in its thioketo form was also coproduced) were obtained according to
Eq. (1):
2(ArS)3As + 3/2O2 → As2O3 + 3ArSSAr .
(1)
Brill and Campbell,4 after 4 h of refluxing a benzene/methanol solution
of PhSeNa and AsCl3, isolated the diselenide PhSeSePh instead of the
ester (PhSe)3As. This result can be rationalized by Eq. (2):
6PhSeNa + 2AsCl3 → 6NaCl ↓ + 2(PhSe)3As 3−/2→O2 As2O3 ↓
+3PhSeSePh,
(2)
To the best of our knowledge, there are no reports in the literature
on the air oxidation of aromatic trithioarsenites except for the obser-
vation previously mentioned.3 In order to understand the effect of the
trithioarsenite structure on its air oxidation, compounds 1–7 were pre-
pared having electron-donating and electron-withdrawing para sub-
stituents. The esters 8 and 9 contain an electron-withdrawing pyridine
group and seem to be interesting ligands containing As, S, and N and
As, S, and O donor atoms.
In this article we present our results on the air oxidation of the aro-
matic trithioarsenites 1–9 in solution and compared the relative rates
of the air oxidation of 1–9 vis-a-vis the air oxidation of their correspond-
ing thiols. The results are best interpreted by assuming O2 binding to
As(III).

Air Oxidation of Triaryl Trithioarsenites
365
RESULTS AND DISCUSSION
On the Preparation of Aromatic Trithioarsenites
We have developed a simple method for the preparation of aliphatic,
(RS)3As, and aromatic, (ArS)3As, trithioarsenites by reacting As2O3
with equivalent amounts of thiol in methanol, ethanol, or water,3,5
thus avoiding the use of the liquid AsCl3 and the preparation of a
salt (usually sodium) of the thiol.6 However, compounds with pro-
nounced thioketo rather than thiol character, e.g., the antithyroid agent
2-mercapto-1-methylimidazole, do not react with As2O3.5 Moreover, the
sodium salt of 2-mercapto-1-methylimidazole does not react with AsCl3
(T. D. Sideris, unpublished results). 4-Mercaptopyridine, which exists
predominantly as pyrid-4-thione,7 reacts with As2O3 in methanol. The
colored solid obtained is not the expected tris(4-pyridyl) trithioarsenite
but probably a mixture of As2O3 and cyclo-As4S4 containing 4-pyridyl
group(s). Such mixtures have been obtained previously by reacting
(ArS)3As with S8 in the presence of triethylamine as a catalyst without
exclusion of air.3 These sulfur-containing molecules probably arise from
the reaction of As2O3 with HS−/H2S. The latter most likely comes from
the attack of another 4-mercaptopyridine molecule.8
The thiols 2-mercaptopyridine and 2-mercaptopyridine N-oxide
also exist predominantly as the tautomeric pyrid-2-thione and 1-
hydroxypyrid-2-thione.7,9 The products obtained upon their reaction
with As2O3 are the aromatic trithioarsenites 8 and 9 as evidenced by
their solid state IR spectra. Thus, the spectrum of 8 resembles the spec-
trum of bis(2-pyridyl) disulfide,10 except that the two peaks at 1149
(mw) and 1114 (s) of the latter are found as a somewhat broad peak
centered at 1130 cm−1 (m) in 8. The solid state IR spectrum of 9 is sim-
ilar to that 2,2ꢀ-dithiobis(pyridine N-oxide).10 In the spectrum of 2,2ꢀ-
dithiobis(pyridine N-oxide) two peaks appeared at 1250 (vs) and 1226
(s), which fall in the region 1300–1200 cm−1 for the N+-O− stretching vi-
bration. In the spectrum of 9, which should be approximately the same
as that of the disulfide, these peaks changed intensity and shifted to
1260 (w) and 1206 cm−1 (vs), probably indicating coordination of the
O− to As(III) to give an As(III) complex, based on the observation that
the N+ O− stretching vibration in pyridine N-oxide appears at 1242
cm−1 and on coordination to Pt(II) is shifted to 1235 cm−1 11
.
Because the esterification gives a solid trithioarsenite from the solid
As2O3, a 24–48 h stirring was used. In view of the facile autoxidation
of some trithioarsenites in solution, especially 2, 8, and 9, deaerated
solvent should be used for their preparation. However, 2, 8, and 9 were
found to be stable as solids at −20◦C without special precautions for at
least 5 months.

366
M. N. Haikou and P. V. Ioannou
Air Oxidation of the Trithioarsenites 1–9 Versus the Air
Oxidation of Their Parent Thiols
The oxidation of thiols to disulfides by dioxygen is faster in alkaline
solutions, is fast in aprotic (e.g., N, N-dimethylformamide) but slow in
protic (e.g., MeOH) anhydrous solvents; the rates (in methanol) depend
on the nature of the thiol (e.g., n-BuSH > p H2N Ph SH > Ph SH
.
1−
˙
ꢁ p O2N Ph SH). It is a free radical process involving RS, O2 , and
2−
O2 species generated by the reaction of RS− with O2 in a rate deter-
mining step.12 The autoxidation of thiols in neutral media at r.t. does
not take place in the absence of radical initiators, e.g., trace metals, UV,
and peroxides.13
The data in Table I show that 4-chloro and 4-nitrothiophenol are
not autoxidized, while the other para substituted thiophenols as well
as 2-mercaptopyridine and 2-mercaptopyridine N-oxide (the latter two
existing predominantly in their thioketo forms7,9) dissolved in nondried
solvents are oxidized by air to a very small extent to their disulfides,
which is consistent with the proposal12 that it is the anion, ArS−, that
reacts with O2. The addition of methanol to a chloroform solution of
thiophenol does not seem to increase its autoxidation to diphenyl disul-
fide.
From Table I it can be seen that the esters 1–9 are air oxidized to
As2O3 (and disulfides) to various degrees depending on the nature of the
aryl group and the solvent. This is a clear indication that the As(III)
in the esters 1–9 can bind and, thus, activate the dioxygen towards
oxidation of the bound ArS- ligands.
The Effect of the Aryl Group on the Air Oxidation
of the Trithioarsenites 1–9
The ease of the oxidative decomposition of 1–7 does not seem to follow
a linear trend when the Hammett para substituent constants σ14,15 are
considered. In fact, the trend seems to parallel the development of a pos-
itive charge on sulfur in diaryl disulfides, i.e., electron-donating groups
result in a low, constant positive charge, while this charge increases
with the electron-withdrawing power of the para substituents of the
phenyl groups.16 The data of Table I indicate that, in CHCl3 or CHCl3-
rich solvents, electron-donating groups tend to disfavor while electron-
withdrawing groups tend to favor the oxidative decomposition of 1–7.
The esters 8 and 9, also having electron-withdrawing aryl groups, de-
composed by air, much faster than 1–7, to As2O3 and a mixture of their
disulfide and free “thiol” instead of only the disulfide.
From the literature it is known that the sensitized photooxygenation
(i.e., with singlet dioxygen, 1O2) of aliphatic sulfides (the aromatic ones

Air Oxidation of Triaryl Trithioarsenites
367
TABLE I Percent of Oxidative Decomposition, Based on the Isolated
As2O3, of the Triaryl Trithioarsenites 1–9 Dissolved in a Solvent
(∼ 20 mM) and Stirred in Air at r.t. and Percent of the Parent Thiol
Oxidized by Air to Its Disulfide Under the Same Conditions.
Duplicate (in Most Cases) Experiments
Disulfide
Hammett
Time
(hours)
Decomposition
(%)
from
thiol (%)
Ester
Solvent
σ-value15
1
Me2CO/CHCl31 : 9
Me2CO/MeOH1 : 2
CHClb3
72
72
72
24
72
72
72
72
72
72
72
72
72
8
8–14
6–12
10a
−0.660
−0.370
5–10a
—
2
—
MeOH
100a
100a
5–10a
—
MeOHc
3
4
CHCl3
13–19
11–14
37–41
8–16
64–66
85–89
30–36
69–73
100e
−0.151
Dd
Me2CO/CHCl3 1 : 4
Me2CO/MeOH 1 : 1
CHCl3
CHCl3/MeOH 3 : 1
CHCl3/MeOH 3 : 2
CHCl3
0.00
<5a
—
5
0.00
Dd
Dd
Dd
6
7
8
+0.227
+0.778
—
NDd
NDd
<5a
—
CHCl3
CHCl3
CH2Cl2
48
7
7
94e
c
9
MeOH/CHCl3 1 : 3
100e
—
—
—
<5a
MeOH
MeOH/CH2Cl2 1 : 3
100e
48
70 f
c
a
Visual estimation of TLC spots.
Suspension, 4 mM.
Dry solvent/pure dioxygen.
The thiol and its disulfide have the same R values on TLC. D = disulfide was
b
c
d
f
detected and ND = disulfide was not detected after capturing the thiol with mercury(II).
e
Thiol and disulfide were produced (see Experimental section).
Calculated from the isolated thiol plus disulfide.
f
being unreactive because they do not have an α-H) to their sulfoxides
is favored in protic solvents (e.g., methanol) and the first intermediate
that is formed, the persulfoxide R2S(O2), has a zwitterionic character,
R2S+ O O−.17−19 Trialkylphosphines, R3P, react with dioxygen in air
giving a variety of products that were explained by assuming that 3O2
(triplet dioxygen) reacted with the R group rather than with P(III),20
while in the gas phase reaction of Me3P with 3O2, the formation of the
diradical, Me3P. O O., was suggested as the first intermediate.21 An
analogous diradical, R2HP. O O., has also been suggested as an inter-
mediate in the air oxidation of dialkylphosphines, R2HP, to dialkylphos-
phine oxides, R2HP O, in isopropyl alcohol22 and it is different from
that obtained by dioxygen oxidation of dimethylarsine, Me2HAs, i.e.,

368
M. N. Haikou and P. V. Ioannou
Me2As O O.,23,24 en route to cacodyl oxide, Me2As O AsMe2, and ca-
¨
codylic acid, Me2AsO2H.25 Theoretical calculations26 on the interac-
1
tion of PH3 and Me3P with O2 show that the species R3P. O O. or
R3R+ O O− are not stable as intermediates. The energy minima cor-
respond to the phosphadioxiranes 10 and 11 and the addition of water
to 10 exothermally gives 12.
The oxidative decomposition of the esters 1–9 in nondried solvents
can be interpreted by two routes. The first, “hydrolysis-oxidation,”
involves hydrolysis of the trithioarsenite and then oxidation of the thiol
by dioxygen, (Eqs. (3) and (4)):
2ArSSAr + 6H2O → 6ArSH + 2As(OH)3 → As2O3 ↓ + 3H2O (3)
4ArSH + O2 → ArSSAr + 2H2O.
(4)
This route, if followed, should be a minor one because trithioarsen-
ites are stable in a neutral environment and unstable in alkaline or
acidic solutions,5,27 and because while the esters 6 and 7 decompose
to As2O3 and disulfide, their parent thiols, 4-chlorothiophenol and 4-
nitrothiophenol, are not oxidized by air (Table I). 4 nitrothiophenol is
not oxidized even in alkaline solutions.12
The second route requires the formation of an (ArS)3As/O2 adduct
and the ability of 3O2 in air to combine with the As(III) in certain com-
pounds has been inferred in previous reports.1−4,23 The adduct can most
likely be a loosely bound complex, (ArS)3As: . . . 3O2, rather than an exci-
1
plex, (ArS)3As:. . . O2. These species can give a diradical or a zwitterion,
respectively, Scheme 1.28,29
For a diradical to be formed, a transfer of a π∗ electron from
3O2 into a contracted30,31 empty 4d orbital of As(III) is envisioned.32
Electron-withdrawing groups on (ArS)3As (i.e., the development of pos-
itive charge on the sulfur atoms bound to As(III)) will contract the
d orbitals to a point favorable for electron transfer to form the di-
radical, and this may explain the facile air oxidation of the esters
6 and 7 (Table I). Electron-donating groups will not contract the d
orbitals, making the electron transfer less favorable. The diradical
(ArS)3As˙ O O. can react with another (ArS)3As molecule to give the
new diradical (ArS)3As· O O As·(SAr)3 which, by homolytic fission

Air Oxidation of Triaryl Trithioarsenites
369
SCHEME 1
of the peroxy bond, will give two molecules of the arsenic(V) ester,
(ArS)3As O, which decompose to As2O3 and disulfide (see next section).
The ester (ArS)3As O can also be produced by attack of an (ArS)3As
molecule at the apical oxygen of an arsenadioxirane, (ArS)3As(O2), (see
ref. 26). These two possibilities can explain the air oxidation of 1–7 in
nonprotic solvents.
The Effect of the Solvent on the Air Oxidation
of the Trithioarsenites 1–9
In nonprotic and nondried solvents, 1–5 were air oxidized to an extent of
10–15% while 6 and 7, having electron-withdrawing groups, were 35%
and 70% air oxidized, respectively. Ester 8 was completely consumed
during the air oxidation in ∼8 h giving As2O3, disulfide, and 80–90%
free “thiol.” Part of the latter arose from the hydrolysis of 8 because in
dry dichloromethane under dioxygen the decomposition was incomplete
after 48 h and the “thiol” was only ∼30%.
In dry methanol under dioxygen, ester 2 was slowly oxidized to
As2O3 and disulfide, but in nondried methanol in air the oxidation was
faster (Table I), indicating involvement of water in the process. In dry
MeOH/CH2Cl2 under dioxygen the consumption of 9 was incomplete
after 48 h, giving As2O3, disulfide (∼50%), and free “thiol” (∼50%), but
in MeOH or in MeOH/CHCl3 the consumption of 9 during its air oxida-
tion was fast, giving As2O3, disulfide (∼60%), and free “thiol” (∼40%).

370
M. N. Haikou and P. V. Ioannou
In the presence of methanol, the air oxidation of 1 was unaffected, while
that of 4 and 5 increased.
In protic solvents the diradical or the arsenadioxirane, Scheme 1,
can be converted to the zwitterion (ArS)3As+ O O−. Methanol can
affect a zwitterion in several ways: It can stabilize it by solvation; it
can (by hydrogen bonding to the −O− terminal) decrease the negative
charge on the oxygen thus facilitating the nucleophilic attact17 of an-
other (ArS)3As to give two molecules of (ArS)3As O; and, finally, can
convert it to a hydroperoxy compound (ArS)3(MeO)As OOH (see ref.
19), which will be more easily attacked by an (ArS)3As nucleophile.
By one of these possibilities, the increased decomposition of 4 and 5,
assuming no water participation, can be rationalized.
Air oxidation of solutions of 1–9 introduces another variable, that
of moisture, especially when methanol is used as solvent or co-
solvent. Entry of a water molecule to the tetracoordinated As(V),
(ArS)3As+ O O−, to give the pentacoordinated As(V) hydroperoxide
analogous to 12 should be favorable due to the bigger size of arsenic
compared to phosphorus.33 The effect of water is most profoundly seen
in the case of 2, 8, and 9. From 8 and 9, As2O3, disulfide, and free “thiol”
are produced, the latter arising from both oxidative decomposition and
hydrolysis of the esters.
The mono esters of arsenic acid, RO AsO3H2, are hydrolytically
very unstable,34 probably because the size of arsenic permits the
easy entry of a water molecule.33 Thioesters of arsenic acid of the
type ArS-AsO3H2, if formed, are also hydrolytically unstable,3 while
those of the type (ArS)2AsO2H and (ArS)3As O, postulated in this
work, once formed have two options: either to hydrolyse to ar-
senic acid, (HO)3As O, and thiol, ArSH, or to suffer a redox reac-
tion giving [HO As O] and [ArS As O] by expulsion of a disul-
fide, ArSSAr. The hydrolysis route does not take place because
As4O6, and not H3AsO4, is produced. We propose that the As4O6
arises from the tetramer (HO As O)4 by dehydration and from the
tetrameric (ArS As O)4 via oxidative hydrolysis. Compounds of the
type RS As O, e.g., (arsenate reductase)-cys S As O, was postu-
lated to hydrolytically give As2O3 and (arsenate reductase)-cys SH.35
The enzyme prevents the oxidation of cysteine to cystine, while in
our case such an inhibition is not possible and a disulfide, ArSSAr, is
produced.
From the results of Brill and Campbell,4 mentioned in the intro-
duction, and the data of Table I, it follows that the ester (PhSe)3As is
oxidized by air much faster than the (PhS)3As, 5. Since the Pauling
electronegativities of sulfur (2.58) and of selenium (2.55) do not differ
appreciably, it seems that the size (covalent radii: S 102, Se 114 pm)

Air Oxidation of Triaryl Trithioarsenites
371
plays a role in the binding of dioxygen to the (ArE)3As (E S or Se). The
structure of the (ArE)3As may also be a factor because the conforma-
tion of 5 in solution36a (but not in the solid state36b) has been shown to
have a “picket-fence” arrangement of the three phenyl groups, which
probably prevents the approach of O2 to As(III), while such a conforma-
tion of (PhSe)3As, due to the bigger size of Se, will not prevent such a
binding.
Some years ago we37 tried the reaction between 5 and n-octyl am-
sylate in dry dichloromethane in an effort to prepare arsonic acids ac-
cording to Eq. (5):
H2O
(PhS)3As + RO − SO2 − C6H4 − NMe+ → R − As+(SPh)3 −→
3
R − AsO3H2.
(5)
However, after 3 days of stirring at r.t. we obtained As2O3 and PhSSPh
(100% oxidative decomposition). This result, which differs from that
shown in Table I, implies that the oxidation of 5 by dioxygen is cat-
alyzed by the amsylate. The mechanism of the catalysis is not yet
known. Another interesting case is the following38: sodium arsen-
ite is nearly unaffected by dioxygen (a 0.12%-per-24-h rate of oxida-
tion to sodium arsenate has been published39) and sodium sulfite is
slowly oxidized by air. However, in the presence of both salts, air oxi-
dized both salts to arsenate and sulfate, and under proper conditions
one molecule of arsenate was produced for every molecule of sulfate
formed.
Summarizing, the results of the air oxidation of the triaryl
trithioarsenites 1–9 reported herein, of triphenyl triselenoarsenite,4
trialkyl trithioarsenites,4,6 diphenyl allydithioarsonite and diphenyl
benzyldithioarsonite,2 and of As(III)/ascorbic acid 1:2 complex1 tend to
indicate that the As(III) in these compounds can bind dioxygen, giving
a diradical L3As. O O., or an arsenadioxirane [L3As(O2)], or a zwitte-
rion L3As+ O O− intermediate, depending on the reaction conditions.
This intermediate in the previously mentioned compounds reacts fur-
ther to give the various observed products. From the limited literature
data37,38 it seems that the binding and/or the reaction of the bound
dioxygen can be “catalyzed” by other nonarsenic-containing molecules,
which themselves can remain unaffected (e.g., amsylate) or be oxidized
(e.g., sulfite).
The ability of As(III) to bind and activate dioxygen may have impli-
cations in chemotherapy or induction of carcinogenesis40 because both
may involve reactive oxygen species.41,42

372
M. N. Haikou and P. V. Ioannou
EXPERIMENTAL
The source and purification of the aromatic thiols used to prepare
the esters 1–3, 5, 7, and 8 have been described.3 4-chlorothiophenol
and 2-mercaptopyridine N-oxide (Aldrich) were used as received. 4-
acetamidothiophenol (Aldrich, 90%) was purified by fractional crystal-
lization (60% recovery) from acetone-petroleum ether, m.p. 155–156◦ C
(lit.16 155–158◦C). 4-mercaptopyridine (Aldrich) was purified by recrys-
tallization from methanol8, m.p. 173–177◦C sinters, 184–189◦C melts to
a red oil with evolution of hydrogen sulfide (lit.8 186◦C). The disulfides of
thiophenol, 4-mercaptophenol, 4-nitrothiophenol, 4-methylthiophenol,
4-aminothiophenol, and 2-mercaptopyridine were isolated as byprod-
ucts of the attempted oxidation of the esters 1–3 and 5–7 by octasulfur.3
4-acetamidophenyl disulfide was prepared by hydrogen peroxide oxi-
dation of a methanolic solution of 4-acetamidothiophenol, m.p. 213–
215◦C (lit.16 150–153◦C, lit.43 218–220◦C). 2,2ꢀ-dithiobis(pyridine N-
oxide) was prepared by hydrogen peroxide oxidation of a methanolic
solution of 4-mercaptopyridine N-oxide, m.p. 174◦C starts darkening,
203◦C dec. (lit.44 235–237◦C, lit.45 205◦C dec., lit.46 200–203◦C dec.).
Its IR (KBr) spectrum was the same as reported.10 Bis(4-chlorophenyl)
disulfide was prepared by hydrogen peroxide oxidation of a methano-
lic solution of 4-chlorothiophenol, m.p. 73–74◦C (lit.47 72◦C). The es-
ters 1–3, 5–7, and 8 have been prepared as described.3 Nondried
AR grade solvents and solutions were deaerated by boiling, flushing
with nitrogen, stoppering, and cooling to r.t. Dichloromethane and
methanol, used in some experiments, were dried over A4 molecular
sieves.
Thin Layer Chromatography, TLC, using silica gel H (Merck), was
run on microslides, always using the appropriate standards. The fol-
lowing developing solvents were used and the R values for the triaryl
f
trithioarsenite, disulfide, and thiol, respectively, were for 1: Et2O, R
f
0.13, 0.54, 0.77; for 2: Et2O/petroleum ether 1:1, R 0.12, 0.38, 0.58; for
f
3: petroleum ether, R 0.22, 0.46, 0.46; for 4: Et2O, R 0.07, 0.47, 0.37; for
f
f
5: petroleum ether, R 0.14, 0.46, 0.46; for 6: petroleum ether, 0.18, 0.57,
f
0.57; for 7: Et2O/petroleum ether 1:3, R 0.0, 0.45, 0.45; for 8: Et2O, R
f
f
0.31, 0.77, 0.31; and for 9: Et2O, R 0.64, 0.0, 0.73. Spots were made vis-
f
ible first with iodine vapors followed by spraying with 35% sulfuric acid
and charring. Compounds containing an ArS- group gave colored spots
before being charred. The pairs thiol/disulfide having the same R val-
f
ues could not be separated using a variety of other developing solvents.
Isolated arsenic(III) oxide was measured by weighing and its pu-
rity was checked by IR48 (sharp peak at 802 cm−1). IR spectra
were obtained on a Perking-Elmer model 16PC FT-IR spectrometer.

Air Oxidation of Triaryl Trithioarsenites
373
Elemental analyses were obtained through the Centre of Instrumental
Analyses, University of Patras, Greece.
Preparation of the Trithioarsenites 4, 6, and 9
Tris(4-acetamidophenyl) trithioarsenite, 4
To
a
deaerated colorless solution of the orange 4-
acetamidothiophenol (524 mg, 3.13 mmol) in methanol (5 mL),
arsenic(III) oxide (103 mg, 0.52 mmol As2O3) was added, and the
suspension was stirred at r.t. for 24 h. The suspension cleared and
the clear pale yellow-green solution was evaporated and dried to give
a yellow-green foam (619 mg), which was recrystallized from boiling
ethyl acetate (15 mL) to give the product (486 mg, 80%) as a white
powder. It is soluble in MeOH and Me2CO, insoluble (at r.t.) in AcOEt
and CHCl3, moderately soluble in boiling AcOEt, and soluble in boiling
chloroform, M.p. ∼135◦C sinters, 171–174◦C melts. Calculated for
C24H24N3O3S3As (M 573.56): C, 50.25; H, 4.22; N, 7.33; S, 16.77%;
r
found: C, 50.12; H, 4.39; N, 7.07; S, 16.03%. IR (KBr): 3300 m, 3246 mw,
3176 mw, 3102 mw, 3048 mw, 1660 s, 1592 vs, 1534 vs, 1490 s, 1394
m, 1370 mw, 1318 s, 1258 mw, 1178 mw, 1041 w, 1014 w, 820 m, 734 w,
702 w, 604 w, 585 w, 516 mw.
Tris(4-chlorophenyl) trithioarsenite, 6
A suspension of arsenic(III) oxide (198 mg, 1 mmol As2O3) and 4-
chlorothiophenol (867 mg, 6 mmol) in deaerated methanol (7 mL) was
stirred at r.t. for 24 h. Centrifugation and washing with methanol
(2 × 2 mL) gave the product 6 (861 mg, 85%) as a white powder sol-
uble in petroleum ether and ether and sparingly soluble in methanol.
M.p. ∼ 70◦C shrinks, 77–78◦C melts. Calculated for C18H12Cl3S3As (M
r
505.76): C, 42.74; H, 2.39; S, 19.02%; found: C, 42.53; H, 2.42; S, 19.55%.
IR (KBr): 1892 vw, 1636 vw, 1568 w, 1472 vs, 1386 m, 1090 vs, 1012 s,
818 vs, 742 w, 542 w, 496 m.
Tris(2-pyridyl N-oxide) trithioarsenite, 9
To a yellowish solution of 2-mercaptopyridine N-oxide (994 mg,
7.8 mmol) in deaerated methanol (10 mL), arsenic(III) oxide (258
mg, 1.3 mmol As2O3) was added, and the suspension was stirred at
r.t. for 48 h. The precipitated product 9 (574 mg, 49%), as a faint
yellowish powder, was obtained by centrifugation and washing with
methanol (1 × 2 mL). It is moderately soluble in methanol and insolu-
ble in Et2O, Me2CO, AcOEt, and CHCl3. M.p. 155–157◦C. Calculated
for C15H12N3O3S3As (M 453.38): C, 39.73; H, 2.67; N, 9.27; S, 21.21%;
r
found: C, 39.41; H, 2.55; N, 9.20; S, 21.45%. IR (KBr): 3442 w, 3062

374
M. N. Haikou and P. V. Ioannou
w, 1586 w, 1542 m, 1460 vs, 1406 s, 1260 m, 1206 vs, 1138 s, 1084 s,
1034 mw, 834 s, 762 s, 694 s, 578 s, 546 m.
Attempted Preparation of Tris(4-pyridyl) trithioarsenite
The reaction of arsenic(III) oxide and 4-mercaptopyridine
(1:6 mol/mol) in deaerated methanol gave yellow, orange, or orange-
brown solids insoluble in all common organic solvents and decomposed
by 2 M sodium hydroxide. Their IR (KBr) spectra were very weak,
indicating low content of the 4-pyridyl group in the solid. The percent
analyses showed very low C, H, and N and very high S contents. The
supernatants contained at least two compounds (by TLC [acetone])
and were not studied further.
Air Oxidation of Triaryl Trithioarsenites
Triaryl Trithioarsenites 1–7
The ester (0.1 mmol) dissolved in a solvent (Table I) (4–6 mL) in a
centrifuge tube was stirred at r.t. in air, replenishing from time to time
the solvent that evaporated. All solutions (except those containing the
ester 2 in methanol) became opalescent and TLC showed that only the
esters and disulfides (when separated from their thiols) were present.
Centrifugation and washing (1 × 1 mL solvent) gave pure (by IR) As2O3
from which the percent decomposition was calculated. The percent de-
composition of 2 in chloroform and in methanol was estimated by TLC.
Tris(2-pyridyl) trithioarsenite, 8
The ester 8 (0.1 mmol) dissolved in chloroform (6 mL) was stirred
in air at r.t. for 8 h. Centrifugation and washing with chloroform gave
pure, by IR, As2O3 (11 mg) corresponding to 100% decomposition. The
supernatant contained (TLC estimation) bis(2-pyridyl) disulfide (∼15%)
and 2-mercaptopyridine (∼85%) and gave a solid, which melted at 118–
121◦C. Pure disulfide melts at 52–53◦C49 and pure thiol melts at 128–
130◦C.50
To the ester 8 (0.25 mmol) dissolved in dry dichloromethane (18 mL)
oxygen was added, stoppered, and stirred at r.t. for 48 h. Centrifugation
and washing with chloroform gave pure, by IR, As2O3 (23 mg), corre-
sponding to 94% decomposition. The supernatant contained (by TLC)
the disulfide (∼70%) and thiol plus 8 (∼30%) and gave a solid, which
melted at 45–47◦C.
Tris(2-pyridyl N-oxide) trithioarsenite, 9
The ester 9 (0.1 mmol) dissolved in methanol (or methanol/chloro-
form 1:3) (6 mL) was stirred in air at r.t. for 7 h. Evaporation, drying
in vacuum, and the addition of acetone (3 mL) precipitated pure, by IR,

Air Oxidation of Triaryl Trithioarsenites
375
As2O3 (11 mg) corresponding to 100% decomposition of 9. The super-
natant contained, by TLC, 2,2ꢀ-dithiobis(pyridine N-oxide) (∼60%) and
2-mercaptopyridine N-oxide (∼40%).
To a solution of 9 (0.23 mmol) in dry methanol (3 mL) and dry
dichloromethane (9 mL) oxygen was added, stoppered, and stirred at
r.t. for 48 h. Evaporation, drying in vacuum, and the addition of acetone
(7 mL) precipitated As2O3 and the insoluble 9, which did not react. The
supernatant contained, by TLC, disulfide (∼50%) and thiol (∼50%) and
gave 61 mg of a semisolid from which a 70% decomposition of 9 was
calculated.
Air Oxidation of Thiols Used to Prepare the Esters 1–9
The parent thiols for the esters 1, 2, 4, 8, and 9 dissolved in a sol-
vent were stirred in air at r.t. and the disulfide produced was visually
estimated from the TLCs.
In order to detect the disulfides produced by air oxidation
of 4-methylthiophenol, thiophenol, 4-chlorothiophenol, and 4-
nitrothiophenol, the free thiol was captured by mercuric acetate
in methanol. Centrifugation and washing with methanol gave the
mercuric mercaptide, ArSHgSAr, and a supernatant. The latter was
evaporated, dried in vacuum, and analyzed by TLC. Thiophenol and
4-methylthiophenol produced disulfides but 4-chlorothiophenol and
4-nitrothiophenol did not (Table I).
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