Kinetic studies on the oxidation of aryl methyl sulfides and sulfoxides by dimethyldioxirane; Absolute rate constants and activation parameters for 4-nitrophenyl methyl sulfide and sulfoxide

Article abstract of DOI:10.1039/b714713a

The oxidations of methyl 4-nitrophenyl sulfide and sulfoxide by dimethyldioxirane, in acetone and mixtures of acetone with water, methanol, acetonitrile and hexane, have been followed by UV-Vis spectroscopy to monitor the decay of the substrates. The data show that, under all the conditions studied, both oxidations obey second-order kinetics. Grunwald-Winstein and Kamlet-Taft analyses of the influence of solvents on the second-order rate constants have been used to obtain mechanistic information on the two reactions. Activation parameters for the two oxidations in acetone and aqueous acetone have been calculated from rate constants for reactions in the temperature range 283-313 K and compared with those from sulfide and sulfoxide oxidations with other oxidants. For sulfoxide oxidations in acetone and 1-20% v/v water in acetone, the results support a concerted nucleophilic displacement by sulfur of oxygen from dimethyldioxirane with the rate being dependent on the solvent's polarity. Sulfide oxidations in acetone and 1-5% v/v water in acetone also proceed by a concerted mechanism. However, in the most polar solvent system studied, 20% v/v water in acetone, the mechanism changes in favour of a two-step reaction involving a betaine intermediate. Importantly, the sulfide oxidation shows a different solvent dependence to that of the sulfoxide, with the rate of oxidation being determined by the hydrogen bond donor capacity and electron-pair donicity of the solvent. This journal is The Royal Society of Chemistry.

Full text of DOI:10.1039/b714713a

View Article Online / Journal Homepage / Table of Contents for this issue
Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Kinetic studies on the oxidation of aryl methyl sulfides and sulfoxides by
dimethyldioxirane; absolute rate constants and activation parameters for
4-nitrophenyl methyl sulfide and sulfoxide†
Peter Hanson,* Ramon A. A. J. Hendrickx‡ and John R. Lindsay Smith*
Received 24th September 2007, Accepted 5th December 2007
First published as an Advance Article on the web 11th January 2008
DOI: 10.1039/b714713a
The oxidations of methyl 4-nitrophenyl sulfide and sulfoxide by dimethyldioxirane, in acetone and
mixtures of acetone with water, methanol, acetonitrile and hexane, have been followed by UV-Vis
spectroscopy to monitor the decay of the substrates. The data show that, under all the conditions
studied, both oxidations obey second-order kinetics. Grunwald–Winstein and Kamlet–Taft analyses of
the influence of solvents on the second-order rate constants have been used to obtain mechanistic
information on the two reactions. Activation parameters for the two oxidations in acetone and aqueous
acetone have been calculated from rate constants for reactions in the temperature range 283–313 K and
compared with those from sulfide and sulfoxide oxidations with other oxidants. For sulfoxide
oxidations in acetone and 1–20% v/v water in acetone, the results support a concerted nucleophilic
displacement by sulfur of oxygen from dimethyldioxirane with the rate being dependent on the solvent’s
polarity. Sulfide oxidations in acetone and 1–5% v/v water in acetone also proceed by a concerted
mechanism. However, in the most polar solvent system studied, 20% v/v water in acetone, the
mechanism changes in favour of a two-step reaction involving a betaine intermediate. Importantly, the
sulfide oxidation shows a different solvent dependence to that of the sulfoxide, with the rate of oxidation
being determined by the hydrogen bond donor capacity and electron-pair donicity of the solvent.
which are sensitive to acid- or base-catalysed solvolysis. This is well
Introduction
illustrated by the successful preparation of aflatoxin B1 exo-8,9-
Dioxiranes can be readily prepared and used in situ by oxidation of
epoxide (4), the carcinogenic metabolite of the mycotoxin aflatoxin
R
ketones with Oxoneꢀ.2 The simple, volatile dioxiranes, dimethyl-
dioxirane (1) and (trifluoromethyl)methyldioxirane (2), have been
the most extensively studied since they can also be isolated as dilute
solutions (ca. 0.1 mol dm−3) in the parent ketone by distillation
from their respective oxidation mixtures3 or be obtained free of
ketone by extraction into chloromethane solvents.4
B1 (3), using dimethyldioxirane,11 when all previous attempts
to bring about this epoxidation with other reagents had failed
(Scheme 1).12 Another example of the use of dioxiranes in synthesis
is in the first successful oxidation of episulfides to episulfones using
(trifluoromethyl)methyldioxirane (2), when a range of alternative
oxidants had been employed without success (Scheme 2).13
Dioxiranes can transfer an oxygen atom to a variety of
substrates under mild conditions, without the requirement for
acid or base catalysis, and have found many applications as
oxidants.5 These oxidations include epoxidation of alkenes2a,b,d,3a,6
and alkynes,4b,7 oxygen transfer to the heteroatom in amines8 and
sulfides,9 and insertion into C–H bonds.3a,10 A clear advantage
of using dioxiranes as oxidants in syntheses is with compounds
Scheme 1
Scheme 2
Department of Chemistry, University of York, Heslington, York, YO10 5DD,
UK. E-mail: ph8@york.ac.uk, jrls1@york.ac.uk
† Electronic supplementary information (ESI) available: Equation
derivation; molar absorbances; absorption decay curve. See DOI:
10.1039/b714713a
The most extensively investigated of the dioxirane oxidations
has been alkene epoxidation, and this has been developed, using
chiral ketones and the in situ protocol for dioxirane synthesis,
into an efficient method for the enantioselective epoxidation of
unfunctionalised alkenes (see for example Scheme 314).15
‡ Present address: Department DMPK & Bio-analysis, AstraZeneca, AB
221 87 Lund, Sweden. E-mail: ramon.hendrickx@astrazeneca.com
762 | Org. Biomol. Chem., 2008, 6, 762–771
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
mixtures of acetone with aprotic and protic co-solvents, show that
in all but the most polar solvent system (20% v/v water in acetone)
both oxidations proceed by a concerted mechanism. In this last
solvent mixture, however, there is clear evidence for a change
from a concerted to a two-step mechanism involving a betaine
intermediate. In this paper we explore the mechanisms of the two
oxidations further and report the first absolute rate constants and
activation parameters for the oxidation of a sulfide and a sulfoxide
by dimethyldioxirane in acetone, aqueous acetone and a selection
of other acetone–co-solvent mixtures. The data are analysed
using the Grunwald–Winstein and Kamlet–Taft equations and the
results provide further evidence for the mechanistic conclusions in
our first paper.
Scheme 3
Alkene epoxidation obeys the second-order rate law, first-order
with respect to both dioxirane and substrate. Hammett plots for
epoxidation of styrenes and ethyl cinnamates with dimethyldioxi-
rane in acetone gave q values of −0.906c and −1.53,16 respectively,
identifying the electrophilic nature of dioxiranes in these reactions.
This information, coupled with the activation parameters reported
for the oxidation of cyclohexene with dimethyldioxirane in acetone
(DH‡ 30.8 kJ mol−1 and DS‡ −149 J mol−1 K−1) suggested a
concerted reaction mechanism involving a spiro-shaped transition
state (5) with partial positive and negative charge on the alkene
and the dioxirane, respectively.6b,17
Results
Kinetics of sulfide and sulfoxide oxidation by dimethyldioxirane
(i) Methodology. Methyl 4-nitrophenyl sulfide and sulfoxide
were selected as representative substrates for kinetic studies from
the twelve methyl substituted-phenyl sulfides and sulfoxides used
in our previous investigation (Scheme 5).1 These compounds have
the lowest rates of oxidation by dimethyldioxirane, which make
them the most amenable for conventional kinetic studies. Further-
more, their UV-Vis absorption maxima, unlike the majority of the
substrates in our previous study, are clear of interference from
the solvent’s absorption, allowing the kinetics to be followed by
monitoring the decrease in the substrate’s absorption with time.
Hammett studies, by Murray and coworkers,18 on the oxidation
of aryl methyl sulfides and sulfoxides with dimethyldioxirane in
acetone gave q values of −0.77 and −0.76 for the respective
oxidations. Here, the signs confirm dioxiranes as electrophilic
oxidants and the magnitudes imply that both oxidations occur
by a concerted oxygen atom-transfer with only partial charge
separation. More recently Asensio et al.19 suggested an alternative
mechanism for sulfide oxidation with dioxiranes, involving a
betaine intermediate 6 which can either eliminate the ketone to give
the sulfoxide or ring-close to the dioxathietane (cyclic sulfurane), 7
(Scheme 4). The key observation was the oxidation of sulfides with
(trifluoromethyl)methyldioxirane to the corresponding sulfones,
even in the presence of an excess of the sulfide. This was accounted
for by the rate of cyclisation of the betaine 6 being greater than
that of the elimination of CF3COCH3 (k2 > k3) and the sulfurane
intermediate reacting with the oxidant much faster (to give the
observed sulfone) than does the parent sulfide (k4 > k1).
Scheme 5
The oxidation of both substrates was studied in acetone and in
a selection of solvents (hexane, acetonitrile, water and methanol)
mixed with acetone. Two reaction protocols were employed:
(a) all the sulfide and some of the sulfoxide oxidations were
carried out with ∼2.5-fold excess of substrate (typically 0.1 ×
10−4 mol dm−3) over oxidant and analysed as second-order
reactions; (b) the remaining sulfoxide oxidations used pseudo-
first-order conditions with a large excess of oxidant over substrate
(under these conditions, the sulfide oxidations were too fast to be
easily studied).
The absorptions of the sulfide, sulfoxide and sulfone overlap and
this needs to be taken into account in both the first- and second-
order protocols. It was confirmed that each compound obeys
the Beer–Lambert law and their molar absorption coefficients,
e, for the solvents and wavelengths used are given in the ESI.†
Dimethyldioxirane in acetone is yellow in colour, however, its
absorption (kmax 336 nm, 1.58
compared to those of the methyl 4-nitrophenyl sulfide, sulfoxide
or sulfone, and it does not interfere with the rate measurements.
Scheme 4
In our previous paper we carried out a detailed analysis of
substituent effects in the oxidation of aryl methyl sulfides and
sulfoxides by dimethyldioxirane.1 Hammett correlations using
relative rate data from competitive oxidations, in acetone and
0.042 m2 mol−1) is negligible,
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 762–771 | 763
©

View Article Online
Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Generally, for unit path length the application of the Beer–
Lambert law gives A0 = [S]0eS and A∞ = [P]∞eP = [S]0eP (for
complete reaction of S) where A0 and A∞ are the initial and final
absorbances, S and P are the substrate and product and eS and eP
their respective molar absorption coefficients. On account of the
overlapping absorptions of substrate and product, the absorbance,
At, at an intermediate time t is given by eqn (1),
Using the procedures described above, the oxidations of methyl
4-nitrophenyl sulfide and sulfoxide in all the solvent systems
were found to obey good second-order kinetics. The reactions of
the sulfoxide under pseudo-first-order conditions showed linear
correlations in the plots of ln[(A0 − A∞)/(At − A∞)] vs. time (in all
cases r2 > 0.999). Likewise, all the sulfide and sulfoxide oxidations
under second-order conditions gave excellent fittings (R2 of >
0.999) to eqn (8) (see, for example, ESI Fig. S1†). Where the
second-order rate constant for sulfoxide oxidation was obtained
by both methods, agreement was also excellent. Each reported
rate constant is the average of the values obtained from at least
five experiments.
At = [S]teS + [P]teP
= [S]teS + ([S]0 − [S]t)eP
= [S]0eP + [S]t(eS − eP)
From these expressions it follows that
(1)
A0 − A∞
eS − eP
At − A∞
eS − eP
(ii) Oxidations in acetone and mixtures of acetone with hex-
ane, acetonitrile, H2O, and methanol. The second-order rate
constants for the oxidation of methyl 4-nitrophenyl sulfide and
sulfoxide in acetone and mixed acetone–co-solvent systems are
recorded in Tables 1 and 2. In our previous study, we employed
DMF (relative permittivity 38.220a) as the co-solvent to increase
the polarity of the solvent, acetone (relative permittivity 20.720a),
while maintaining the aprotic environment.1 However, the slow
oxidation of DMF by dimethyldioxirane limited the use of this
co-solvent to sulfide oxidations only. To avoid this problem in the
present study, the polarity was increased with acetonitrile (relative
permittivity 37.520b), which is not oxidised by dimethyldioxirane
and, as previously, it was decreased by the addition of hexane
(relative permittivity 1.920c). For the sulfide oxidation, increasing
the proportion of hexane in the solvent from 0 to 90% v/v
led to a 2.5-fold decrease and the use of acetonitrile–acetone
[S]0 =
and [S]t =
For the first-order protocol we have, for a substrate S reacting
with a large excess of oxidant,
ꢀ
ꢁ
[S]0
[S]t
ln
= k1t
(2)
Substitution of [S]0 and [S]t from above gives eqn (3),
ꢀ
ꢁ
A0 − A∞
At − A∞
ln
= k1t
(3)
The pseudo-first-order data for sulfoxide oxidations (i.e. S = 9)
were analysed using eqn (3) for absorbance at 330 nm. The slopes
of the linear plots of ln[(A0 − A∞)/(At − A∞)] versus t gave k1
from which, knowing [1]0, the second-order rate constants k2 were
calculated.
For the second-order protocol, we have for a substrate S reacting
with 1,
ꢀ
ꢁ
1
[S]0([1]0 − [P]t)
[1]0([S]0 − [P]t)
Table 1 The second-order rate constants for the oxidation of methyl
4-nitrophenyl sulfide by dimethyldioxirane in selected solvent systems
ln
= k2t
(4)
[1]0 − [S]0
b
Solventa Co-solventa Temperature/K 10−2
k
2(sulfide)/dm3 mol−1 s−1
from which it may be shown (see ESI†) that
exp{([1]0 − [S]0)k2t} − 1
Acetone
100
[P]t = [S]0[1]
(5)
0 [1]0 exp{([1]0 − [S]0)k2t} − [S]0
0
293
293
6.05 0.17
30.8 1.0
Since [P]t = [S]0 − [S]t, eqn (5) may be rearranged to give eqn (6)
Acetone Acetonitrile
50 50
(see ESI),
[1]0 − [S]0
Acetone Hexane
[S]t =
(6)
[1]0
[S]0
100
75
0
25
50
90
294
294
294
294
6.76 0.24
6.26 0.12
4.35 0.13
2.68 0.11
exp{([1]0 − [S]0)k2t} − 1
50
Substitution of [S]t from eqn (6) in eqn (1) gives eqn (7),
10
([1]0 − [S]0)(eS − eP)
Acetone Water
At = [S]0eP +
(7)
[1]0
100
98
95
90
85
80
75
0
2
5
10
15
20
25
294
294
294
294
294
294
294
6.76 0.24
9.79 0.68
12.0 0.6
24.0 1.6
40.3 2.1
47.0 1.9
66.3 2.5
exp{([1]0 − [S]0)k2t} − 1
[S]0
Knowing appropriate parameters [S]0, [1]0, eS and eP, eqn (7)
can, in principle, be used to fit the sulfide or sulfoxide decay
profiles. However, due to the time required for manipulation of
solutions and the reaction cell, there is an uncertain time-lapse,
t0, between the formal onset of reaction and the recording of the
first observation. It is therefore convenient to adjust eqn (7) to
incorporate this [eqn (8)]. The resulting multiparameter fittings
thus lead to evaluation of both k2 and t0.
Acetone Methanol
100
99
90
0
1
10
20
299
299
299
299
7.21 0.17
7.07 0.14
8.73 0.17
13.7 0.8
80
([1]0 − [S]0)(eS − eP)
a Solvent composition in % v/v. b Uncertainties are 95% confidence
intervals.
At = [S]0eP +
(8)
[1]0
[S]0
exp{([1]0 − [S]0)k2(t − t0)} − 1
764 | Org. Biomol. Chem., 2008, 6, 762–771
This journal is
The Royal Society of Chemistry 2008
©

View Article Online
Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Table 2 The second-order rate constants for the oxidation of methyl 4-
Table 3 The temperature dependence of the second-order rate constants,
k2, for the oxidation of methyl 4-nitrophenyl sulfide and sulfoxide by
dimethyldioxirane in acetone
nitrophenyl sulfoxide by dimethyldioxirane in selected solvent systems
b
Solventa
Co-solventa
Temperature/K
k
2(sulfoxide)/dm3 mol−1 s−1
10−2 k2(sulfide)
Temperature/K dm3 mol−1 s−1
/
k2(sulfoxide)
/
a
a
Temperature/K dm3 mol−1 s−1
Acetone
100
100
0
0
293
293
7.06 0.41
7.52 0.42c
288
293
302
308
313
4.88 0.16
6.05 0.17
8.11 0.24
9.68 0.30
11.6 3.8
283
289
293
298
302
3.86 0.15
5.69 0.25
7.06 0.41
10.3 0.3
12.8 0.4
Acetone Acetonitrile
50 50
293
9.58 0.18
Acetone Hexane
a Uncertainties are 95% confidence intervals.
100
50
0
50
85
294
294
294
8.31 0.51c
9.08 0.47c
19.4 0.8c
15
Acetone Water
Table 4 The temperature dependence of the second-order rate constants,
k2, for the oxidation of methyl 4-nitrophenyl sulfide and sulfoxide by
dimethyldioxirane in 20% v/v water in acetone
100
98
95
90
85
80
75
0
2
5
10
15
20
25
294
294
294
294
294
294
294
7.33 0.25
7.54 0.21
8.47 0.28
9.74 0.34
10.5 0.3
12.5 0.4
13.2 0.4
10−2k2(sulfide)
Temperature/K dm3 mol−1 s−1
/
k2(sulfoxide)
/
a
a
Temperature/K dm3 mol−1 s−1
290
295
298
305
309
35.5 1.5
47.0 1.9
53.2 2.0
71.5 2.5
86.0 2.1
290
295
298
305
309
9.25 0.33
12.5 0.4
14.3 0.5
19.5 0.7
25.4 0.6
Acetone Methanol
100
99
80
0
1
20
50
295
295
295
295
8.31 0.51c
8.38 0.58c
8.23 0.58c
7.94 0.69c
a Uncertainties are 95% confidence intervals.
50
a Solvent composition in % v/v. b Uncertainties are 95% confidence inter-
vals. c Values of k2 calculated from k1 from pseudo-first-order conditions.
Table 5 The temperature dependence of the second-order rate constant,
k2, for the oxidation of methyl 4-nitrophenyl sulfide by dimethyldioxirane
in 5% v/v water in acetone
(1 : 1, v/v) resulted in a 4.5-fold increase in k2. By contrast, k2
for the sulfoxide reaction in acetone increased 2.5-fold in 90% v/v
hexane in acetone, and showed a small increase (1.1-fold) in a
50% v/v acetonitrile–acetone mixture.
a
Temperature/K
10−2 2(sulfide)/dm3 mol−1 s−1
k
290
295
298
305
309
10.1 0.3
12.0 0.6
13.6 0.6
16.4 1.1
19.7 1.2
The second-order rate constant for sulfide oxidation was also
increased by the addition of the polar protic co-solvents water and
methanol (relative permittivity 80.220d and 33.0,20e respectively).
Thus, changing the water content from 0 to 25% v/v resulted in
a 10-fold increase in k2, and for methanol a somewhat smaller
4.3-fold increase was obtained with a 0 to 50% v/v change in
co-solvent concentration. The corresponding changes in the rate
constant for the sulfoxide oxidation were significantly smaller, a
1.8-fold increase and ∼0, respectively.
a Uncertainties are 95% confidence intervals.
The data reveal, in agreement with our previous study on the
relative rates of oxidation of aryl methyl sulfides and sulfoxides,
that whereas the sulfoxide oxidation is not greatly affected by
changes in solvent properties, that of the sulfide is strongly
favoured by solvents that are hydrogen-bond and/or electron-pair
donors. These observations are investigated in more detail below
using Grunwald–Winstein and Kamlet–Taft analyses.
(iii) Activation parameters. The oxidation of methyl 4-
nitrophenyl sulfide in acetone and aqueous acetone (5 and
20% v/v) was carried out at five temperatures between 283 and
313 K, and likewise that of the sulfoxide in acetone and aqueous
acetone (20% v/v). The second-order rate constants from these
studies (Tables 3–5) were used to obtain the activation parameters
DH‡ and DS‡ from their respective Eyring plots (see for example
Fig. 1 and 2) (Table 6).
Fig. 1 Eyring plot for the oxidation of methyl 4-nitrophenyl sulfide by
dimethyldioxirane in acetone.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 762–771 | 765
©