Iron(III)-Ethylenediaminetetraacetic Acid Mediated Oxidation of Thiols to Disulfides with Molecular Oxygen

Article abstract of DOI:10.1039/a702061i

Fe^IIIEDTA in aqueous methanol offers a simple environmentally acceptable synthetic tool for oxidizing thiols to the corresponding disulfides by molecular oxygen in excellent yields, under mild conditions and devoid of side reactions.

Full text of DOI:10.1039/a702061i

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300 J. CHEM. RESEARCH (S), 1997
J. Chem. Research (S),
1997, 300–301†
Iron(III)–Ethylenediaminetetraacetic Acid Mediated
Oxidation of Thiols to Disulfides with Molecular Oxygen†
Tumula Venkateshwar Rao,a Bir Sain,a Pappu S. Murthy,a Turaga S. R. Prasada
Rao,a Ajay K. Jainb and Girish C. Joshi*a
aIndian Institute of Petroleum Dehradun-248 005, India
bDepartment of Chemistry, University or Roorkee, Roorkee-247 667, India
FeIII–EDTA in aqueous methanol offers a simple environmentally acceptable synthetic tool for oxidizing thiols to the
corresponding disulfides by molecular oxygen in excellent yields, under mild conditions and devoid of side reactions.
FeIII–EDTA, O2
The conversion of thiols into the corresponding disulfides
R
S
H
R
S
S
R
(oxidative S–S coupling) is an important reaction and many
stoichiometric reagents have been reported to be effective
oxidants for it, such as dichromates,1 chlorochromates,2
manganese dioxide,3 diethyl azodicarboxylate,4 halosilane–
chromium trioxide,5 nickel peroxide,6 chromium peoxide,7
pH 7.8–9.6, aq. MeOH
1
2
R = Ph, 4-MeC6H4, 4-MeOC6H4, 2-pyridyl, PhCH2, Bun, n-C5H11
n-C7H15, n-C8H17
,
diaryl telluroxides,8 tetrabutylammonium cerium(IV
)
Scheme 1
nitrate,9 sodium perborate10 and silver trifluoromethane-
sulfonate.11 Owing to the growing environmental concerns
surrounding the use of toxic and dangerous oxidants, oxida-
tive catalytic transformations of organic compounds with
molecular oxygen have become an area of continued
research and development in recent years.12 The catalytic
oxidation of thiols present in petroleum fractions to dis-
ulfides with molecular oxygen under strongly alkaline condi-
tions using metal phthalocyanines as catalysts has been
extensively studied.13 However, there are only a few reports
on the synthesis of disulfides by catalytic oxidation of thiols
using molecular oxygen as the primary oxidant, with basic
alumina,14 cobalt tetrasulfonatophthalocyanine,15 intercala-
ted [MOVIO2(O2CC(S)Ph2)2]2ꢀ in ZnII–AlIII-layered double
hydroxide16 and cobalt chlorate17 all having been used as
catalysts. The subject has been comprehensively reviewed by
Uemura.18 Among the transition metals, iron is singled out
as being non-toxic19 and more emphasis is being given on the
use of iron-based systems for oxidation.20 Earlier, we
reported iron(III)–ethylenediaminetetraacetic acid (FeIII–
EDTA) mediated autoxidation of 2,6-di-tert-butylphenol
and substituted hydroquinones.21 We now report for the first
time FeIII–EDTA22 catalysed oxidation of thiols (1) to di-
sulfides (2) with molecular oxygen (Scheme 1).
fate solution and raising the pH of the mixture to 8.0 by
addition of sodium carbonate solution. The oxidation experi-
ments were carried out by bubbling molecular oxygen into a
solution of the thiol in 80% aqueous methanol containing
FeIII–EDTA (10 mol% of the thiol) at specified pH under
ambient conditions (Table 1). A wide variety of thiols (aro-
matic, aliphatic and heterocyclic) were selectively oxidized to
their corresponding disulfides in near quantitative yields
without any evidence for the formation of the corresponding
sulfonic acid. Under these reaction conditions aromatic
thiols in general were found to be more reactive than ali-
phatic ones. Among the aliphatic thiols the reactivity was
found to decrease with increasing carbon chain length and
was strongly dependent upon the pH of the medium. While
aromatic thiols could be oxidized at a pH of about 8 in a
reasonable reaction time, the aliphatic thiols required a
higher pH. To evaluate the catalytic effect of FeIII–EDTA in
this reaction, a parallel blank experiment was carried out with
benzenethiol. The conversion of benzenethiol into its di-
sulfide was 73% after 4 h without FeIII–EDTA, while conver-
sion was quantitative within 20 min in the presence of FeIII–
EDTA.
The oxidation of thiols to disulfides by molecular oxygen
under alkaline conditions has been reported to proceed
through a radical pathway involving one-electron transfer
An FeIII–EDTA (0.1
EDTA disodium salt solution to an ammonium iron(III) sul-
M
) solution was prepared by adding
Table 1 FeIII–EDTA catalysed oxidation of thiols (1) to disulfides (2) by molecular oxygena
Mp or bp (Torr) (T/°C)
Disulfide
(2)
Reaction
(t/h)
Yieldb
(%)
R
pH
Found
Lit.
a
b
c
d
e
f
Ph
7.8
7.9
7.8
8.0
7.8
8.5
9.5
9.5
9.5
9.6
0.33
0.75
1.0
0.50
8
96
95
87
84
97
98
93
86
87
88
59–61
47–48
59–6014
4-MeC6H4
4-MeOC6H4
2-Pyridyl
PhCH2
46–4825
43.825
44–45
52–53
52–5325
70–71
69–7014
PhCH2
3
70–71
69–7014
g
h
i
Bun
8
9
12
18
94(6)
88–91(3)14
90–92(1)26
143–147(5)27
178–83(5)27
n-C5H11
n-C7H15
n-C8H17
117(6)
152–154(6)
185–187(6)
j
aThe reaction was carried out with 40 mmol of alkanethiol or 10 mmol of arenethiol. bYield of pure
product isolated by crystallization or distillation.
from the thiolate anion to the molecular oxygen. Metal ions
*To receive any correspondence (e-mail: root%iip@sirnetd.
ernet.in).
†This is a Short Paper as defined in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
are known to catalyse this reaction.23 Accordingly, the mecha-
nistic pathway for the present reaction could be through the
formation of a thiyl radical by single-electron transfer from
the thiolate anion to the FeIII–EDTA, followed by coupling

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J. CHEM. RESEARCH (S), 1997 301
of the radical to yield the disulfide. The FeII–EDTA thus
formed is oxidized to FeIII–EDTA by the molecular oxygen
(Scheme 2).
disulfides were purified either by recrystallization or by vacuum
distillation. The identity of the products was established by com-
parison of their mps (wherever possible), IR and NMR spectra and
GC retention times.
Wubs and Beenackers24 postulated FeIII(OHꢀ)EDTA to
be the active species in the oxidation of H2S by FeIII–EDTA
under alkaline conditions. In accordance with their mechan-
ism, thiols may form complexes with FeIII–EDTA by way of
replacement of OHꢀ and intramolecular electron transfer
from FeIII to the thiolate anion generating a thiyl radical
(Scheme 3).
Received, 25th March 1997; Accepted, 6th May 1997
Paper E/7/02061I
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•
FeIII–EDTA
+
RS–
FeII–EDTA
+
RS
•
RS
•
R
S
S
R
+
RS
•
–
FeII–EDTA
+
O2
FeIII–EDTA
+
O2
Scheme 2
RS–
+
FeIII(OH–)EDTA
FeIII(RS–)EDTA
FeIII(RS–)EDTA
FeIIEDTA
+
•
OH–
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RS
Scheme 3
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EDTA, and again to wine red on complete oxidation of the
thiol to the disulfide, suggesting complex formation between
the thiolate anion and the FeIII–EDTA. In line with the
postulated mechanism, the rate of oxidation would depend
on the concentration of thiolate anion. Since aromatic thiols
have lower pKa values than aliphatic thiols, sufficient avail-
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line with their fast oxidation at pH #8 while aliphatic thiols
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reasonable reaction time thus make FeIII–EDTA an attrac-
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Experimental
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General Procedure for the Oxidation of Thiols by Molecular Oxygen
in the Presence of FeIII–EDTA.sA solution of the thiol (10 mmol)
in 80% aqueous methanol (50 ml) containing FeIII–EDTA (0.1
mmol; 10 ml of 0.1
M
solution) was taken in a two-necked round-
bottomed flask fitted with gas delivery tube and a condenser. The
pH of the solution was adjusted by adding a few drops of an alkali
solution and oxygen gas was passed into the solution at 30 °C for a
specified period (Table 1). The completion of the reaction was
indicated by the colour change of the reaction mixture from bluish
green to wine red. The major portion of the methanol was then
removed by distillation under reduced pressure, followed by dilu-
tion of the reaction mixture with water (40 ml) and extraction with
dichloromethane (3Å30 ml). The combined dichloromethane
extract was washed with water and dried (Na2SO4). Removal of the
solvent under reduced pressure yielded the desired disulfide. The
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