Kinetic and equilibrium studies of σ-adduct formation and substitution in the reactions of sulphite ions with some alkyl and aryl ethers and thioethers

Article abstract of DOI:10.1002/(SICI)1099-1395(1998110)11:11<787::AID-POC38>3.0.CO;2-0

Kinetic and equilibrium results are reported for the reactions of sulphite with the ethyl and phenyl ethers of 2,4,6-trinitrophenol and 2,4,6-trinitrothiophenol in 80/20 (v/v) water/DMSO. In each case 1:1 and 1:2 adducts are observed by reaction of sulphite at one or two unsubstituted ring positions respectively. In the case of the ethyl derivatives these adducts are long-lived; however, the phenyl derivatives rapidly yield 2,4,6-trinitrobenzene-sulphonate, the substitution product. This difference is attributed to a change in the nature of the rate-determining step, from nucleophilic attack with the phenyl derivatives to leaving group departure with the alkyl derivatives.

Full text of DOI:10.1002/(SICI)1099-1395(1998110)11:11<787::AID-POC38>3.0.CO;2-0

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 787–792 (1998)
Kinetic and equilibrium studies of s-adduct formation and
substitution in the reactions of sulphite ions with some
alkyl and aryl ethers and thioethers
Michael R. Crampton* and Anthony J. Holmes
Chemistry Department, Durham University, Durham DH1 3LE, UK
Received 24 November 1997; accepted 22 December 1997
ABSTRACT: Kinetic and equilibrium results are reported for the reactions of sulphite with the ethyl and phenyl
ethers of 2,4,6-trinitrophenol and 2,4,6-trinitrothiophenol in 80/20 (v/v) water/DMSO. In each case 1:1 and 1:2
adducts are observed by reaction of sulphite at one or two unsubstituted ring positions respectively. In the case of the
ethyl derivatives these adducts are long-lived; however, the phenyl derivatives rapidly yield 2,4,6-trinitrobenzene-
sulphonate, the substitution product. This difference is attributed to a change in the nature of the rate-determining
step, from nucleophilic attack with the phenyl derivatives to leaving group departure with the alkyl derivatives.
1998 John Wiley & Sons, Ltd.
KEYWORDS: nucleophilic aromatic substitution; Meisenheimer complexes; nucleophilic reactivity; trinitro-
aromatics
INTRODUCTION
respectively. Hence we were interested in the possibility
of observing nucleophilic substitution in these systems.
It is known that sulphite readily forms s-adducts by
reaction with electron-deficient aromatic substrates.1,2
Thus reaction at unsubstituted ring positions of 1-X-
2,4,6-trinitrobenzenes, 1, has been found to yield adducts
2 with 1:1 stoichiometry or 3 with 1:2 stoichiometry.3–8
Reports of attack at substituted ring positions leading to
nucleophilic displacement are relatively scarce, although
it is known that substitution of halide ions leads to the
formation of derivatives of benzene sulphonic acid,9,10
and there is one early report of the formation of an adduct
by attack at the 1-position of 2,4,6-trinitrobenzalde-
hyde.11
RESULTS AND DISCUSSION
Kinetic and equilibrium measurements were made with
four substrates, 1a–1d. The phenyl ether and thioether
were relatively insoluble in water, so all measurements
were made in water/dimethyl sulphoxide (80/20, v/v).
3
The ionic strength was maintained at I = 0.3 mol dm
using sodium sulphate as compensating electrolyte.
1
The results of UV/visible and H NMR spectroscopy
provide evidence that reaction with sulphite involves the
processes shown in Scheme 1. The UV/visible spectra of
the ethyl ether 1a and ethyl thioether 1b in the presence
of low (ca 10 3 mol dm 3) concentrations of sulphite are
typical of 1:1 adducts1,3 with ꢀmax 450 and 550 nm
(shoulder). At higher sulphite concentrations the spectra
show single absorption maxima, at 430 nm in the case of
1a and 450 nm for 1b. The latter spectra are consistent
with formation of adducts with 1:2 stoichiometry.
Confirmation that sulphite addition is occurring at
unsubstituted ring positions comes from 1H NMR
measurements in deuterium oxide/dimethyl sulphoxide
[2H6] 80/20 (v/v). Thus the spectrum of 1b in the
presence of a fourfold excess of sulphite shows a singlet
at ꢁ 6.01 representing the two ring hydrogens of 3b. The
side chain ethyl group gives a triplet (J 7.4 Hz) at ꢁ 1.06
for the methyl hydrogens and two multiplets at ꢁ 3.00 and
3.13 for the methylene hydrogens. The non-equivalence
Here we compare the reactions with sulphite of the
ethyl and phenyl ethers of 2,4,6-trinitrophenol and 2,4,6-
trinitrothiophenol. It is known12,13 that phenoxide and
thiophenoxide are considerably better leaving groups
than their aliphatic analogues, ethoxide and thioethoxide
*Correspondence to: M. R. Crampton, Chemistry Department,
Durham University, Durham DH1 3LE, UK.
1998 John Wiley & Sons, Ltd.
CCC 0894–3230/98/110787–06 $17.50

788
M. R. CRAMPTON AND A. J. HOLMES
Scheme 1
of these hydrogens indicates restricted rotation about the
S-CH2 bond in the adduct. There was no evidence for cis–
trans isomerism in 3b as has been observed in the 2:1
adduct from 1,3,5-trinitrobenzene.4,14,15 The NMR spec-
trum was unchanged after 1 h, indicating that nucleo-
philic displacement of the ethylthio group was a very
slow process. NMR evidence has been presented
previously3 showing that the 1:2 adduct from methyl
2,4,6-trinitrophenyl ether results from sulphite attack at
two unsubstituted ring positions; the ethyl ether is
expected to behave analogously to give 3a.
(shoulder)) and 2d (ꢀmax 450 and 550 nm (shoulder)) at
low sulphite concentrations, and adducts 3c (ꢀmax 490
nm) and 3d (475 nm) at higher sulphite concentrations.
However, in contrast with the behaviour of the ethyl
derivatives, the visible absorption faded rapidly and the
final spectra were identical to those of the substitution
product 4 in the reaction medium. Confirmation that
substitution occurs rapidly in these systems comes from
NMR measurements. The spectrum of 1c (0.05 mol
dm 3) in the presence of sulphite (0.15 mol dm 3) gave a
band at ꢁ 8.73, the position expected for the substitution
product 4, together with multiplets at ꢁ 6.50 and 7.00 due
to the displaced phenoxy group. In addition, small bands
The UV/visible spectra of the phenyl derivatives 1c
and 1d produced on initial mixing with sulphite indicate
formation of the adducts 2c (ꢀmax 450 and 530 nm
Table 2. Kinetic data for reaction of 1b with sulphite in 80/
20 (v/v) water/DMSO at 25°C
Table 1. Kinetic data for reaction of 1a with sulphite in 80/
20 (v/v) water/DMSO at 25°C
[Na2SO3]@
1 b
1 c
1 d
1 e
[Na2SO3]@
(mol dm 3)a kfast@(s
)
kcalc@(s
)
kslow@(s
)
kcalc@(s
)
1 b
1 c
1 d
1 e
(mol dm 3)a kfast@(s
)
kcalc@(s
)
kslow@(s
)
kcalc@(s
)
0.001
0.002
0.003
0.004
0.007
0.010
0.020
0.040
0.060
0.100
4.7
7.7
10
4.9
7.5
10
0.106
0.145
0.19
0.23
0.44
0.60
1.20
2.5
0.098
0.153
0.21
0.26
0.44
0.62
1.2
2.4
3.6
6.0
0.001
0.002
0.004
0.007
0.010
0.020
0.040
0.060
0.100
16
21
30
52
70
130
–
16
22
34
52
70
130
–
0.23
0.27
0.29
0.51
0.65
1.20
2.35
3.4
0.22
0.26
0.35
0.51
0.67
1.2
2.3
3.4
5.6
12
20
28
13
20
28
54
54
105
155
260
105
157
260
–
–
–
–
3.6
6.1
6.2
a
3
a
3
Constant ionic strength, [Na2SO3] ‡ [Na2SO4] = 0.1 mol dm
.
Constant ionic strength, [Na2SO3] ‡ [Na2SO4] = 0.1 mol dm
.
b Colour-forming reaction at 550 nm.
Colour-forming reaction at 550 nm.
b
c
c
1
1
1
1
Calculated from eqn (1) with k1 = 6000 dm3 mol
s
and k
=
Calculated from eqn (1) with k1 = 2600 dm3 mol
s
and k
=
1
1
1
1
10 s
.
2.3 s
.
d Fading reaction at 550 nm.
Fading reaction at 550 nm.
d
e Calculated from eqn (2) with k2 = 55 dm3 mol 1 s 1, k 2 = 0.20 s
Calculated from eqn (2) with k2 = 60 dm3 mol
s
1, k2 = 0.07 s
1
e
1
1
and K1 = 600 dm3 mol
.
and K1 = 1120 dm3 mol
.
1
1
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REACTIONS OF SULPHITE IONS WITH ETHERS AND THIOETHERS
789
Table 3. Kinetic data for reaction of 1c with sulphite in 80/20 (v/v) water/DMSO at 25°C
[Na2SO3]@
3 a
1 b
1 c
1 d
1 e
1 f
1 g
(mol dm
)
kfast@(s
)
kcalc@(s
)
kslow@(s
)
kcalc@(s
)
ksub@(s
)
kcalc@(s
)
0.001
0.002
0.004
0.007
0.010
0.020
0.040
0.060
0.100
22
46
78
135
196
–
–
–
–
24
43
81
138
195
–
–
–
–
–
–
–
–
2.1
2.4
3.1
3.6
4.6
–
–
–
–
2.2
2.5
3.0
3.6
4.7
0.0147
0.0152
0.0168
0.0180
0.0168
0.0160
0.0148
0.0121
0.0109
–
0.0168
0.0173
0.0171
0.0170
0.0149
0.0122
0.0103
–
a
3
Constant ionic strength, [Na2SO3]‡[Na2SO4] = 0.10 mol dm
.
b Colour-forming reaction at 550 nm.
c
1
1
1
Calculated from eqn (1) with k1 = 19 000 dm3 mol
s
and k 1 = 5 s
.
d Fading reaction at 550 nm.
Calculated from eqn (2) with k2 = 28 dm3 mol
s
s
1, k 2 = 1.9 s 1 and K1[SO32-]1.
e
1
f Fading reaction at 550 nm.
g Calculated from eqn (3) with k3 = 74 dm3 mol
1, K1 = 3800 dm3 mol and K2 = 14.7 dm3 mol
.
1
1
1
Table 4. Kinetic data for reaction of 1d with sulphite in 80/20 (v/v) water/DMSO at 25°C
[Na2SO3]@
3 a
1 b
1 c
1 d
1 e
1 f
1 g
(mol dm
)
kfast@(s
)
kcalc@(s
)
kslow@(s
)
kcalc@(s
)
ksub@(s
)
kcalc@(s )
0.001
0.002
0.004
0.007
0.010
0.020
0.040
0.060
0.080
0.100
6.7
9.6
16
6.7
10.4
18
28
40
77
150
225
–
–
–
–
–
0.41
0.40
0.48
0.55
0.67
0.73
0.91
–
–
–
0.41
0.42
0.46
0.55
0.64
0.74
0.83
0.050
0.070
–
0.082
0.078
0.075
0.053
0.044
0.041
–
0.049
0.064
–
0.076
0.076
0.070
0.059
0.051
0.045
–
25
42
78
150
225
–
–
a
3
Constant ionic strength, [Na2SO3]‡[Na2SO4] = 0.10 mol dm
.
b Colour-forming reaction at 550 nm.
c
1
1
1
Calculated from eqn (1) with k1 = 3700 dm3 mol
s
and k 1 = 3 s
.
d Fading reaction at 550 nm.
e
1
1
Calculated from eqn (2) with k2 = 4.5 dm3 mol 1, k 2 = 0.38 s and K1 = 1230 dm3 mol
.
f Fading reaction measured at 550 and/or 480 nm.
g Calculated from eqn (3) with k3 = 110 dm3 mol 1 s 1, K1 = 1230 dm3 mol 1 and K2 = 12 dm3 mol
.
1
were observed at ꢁ 5.88 and 8.34 attributable7 to the
adduct formed by attack of sulphite at the 3-position of
the substitution product 4.
individual rate constants were obtained using an iterative
procedure minimizing the sums of the squares of the
differences between observed and calculated values.
For the phenyl derivatives 1c and 1d, three rate
processes were observable. The first two correspond to
equilibration of the substrate with adducts 2 and 3
respectively. The slowest process leads to the substitution
product 4, and measured rate constants for this process
are designated ksub. The assumption that substitution
involves attack by sulphite on the substrate itself and not
on the adducts 2 or 3 leads to
Kinetic measurements were made by stopped-flow
spectrophotometry with sulphite concentrations in large
5
excess of the substrate concentrations (2 Â 10 mol
dm 3). With the ethyl derivatives 1a and 1b, two rate
processes, well separated in time, were observed. These
are attributed to equilibration of the substrate with
adducts 2 and 3 respectively so that the appropriate rate
equations6 are
kfast ˆ k ‡ k1‰SO2
Š
ꢀ1†
ꢀ2†
k3‰SO23
Š
1
3
ksub
ˆ
ꢀ3†
2
2
k2K1‰SO23
Š
1 ‡ K1‰SO23 Š ‡ K1K2‰SO23
Š
kslow ˆ k
‡
2
1 ‡ K1‰SO23
Š
Data are in Table 3 and Table 4 and give excellent fits
with eqns (1)–(3). It is interesting that, as predicted by
eqn (3), values of ksub increase with increasing sulphite
The experimental data in Tables 1 and 2 give an
excellent fit with these equations. Best values of
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790
M. R. CRAMPTON AND A. J. HOLMES
Table 5. Summary of rate and equilibrium dataa in 80/20 (v/v) water/DMSO at 25°C
1a
1b
1c
1d
1
1
1
k1@(dm3 mol 1 s
)
)
)
6000 Æ 100
10 Æ 0.6
2600 Æ 100
2.3 Æ 0.2
19000 Æ 1000
5 Æ 1
3700 Æ 100
3 Æ 1
1
k
1@(s
)
1 b
K1@(dm3 mol
)
600 Æ 30
1100 Æ 100
60 Æ 5
3800 Æ 500
28 Æ 2
1200 Æ 400
4.5 Æ 0.5
0.38 Æ 0.03
12 Æ 2
k2@(dm3 mol 1 s
55 Æ 5
1
k
2@(s
)
0.20 Æ 0.02
280 Æ 40
0.07 Æ 0.01
860 Æ 200
Not observed
1.9 Æ 0.1
15 Æ 2
1
K2@(dm3 mol
)
k3@(dm3 mol 1 s
Not observed
74 Æ 5
110 Æ 10
P
1
2
a
3
I ꢂ
cizi2 = 0.3 mol dm
.
b K1 = k1@k and K2 = k2@k
.
2
1
concentration, reaching a maximum when [SO32-] ꢁ
0.005 mol dm 3, and then decrease as the sulphite
concentration is increased further. It is worth nothing that
a plot for 1c of kfast vs [SO32-] had a small intercept which
did not allow an accurate determination of k 1. However,
an acceptable fit of the data for eqn (3) could be obtained
only with a value for K1 of 3800 Æ 500 dm3 mol 1. This
leads to a value for k 1 (ꢂk1/K1) of 5 Æ 1 s 1. For both 1c
and 1d the amplitude of the process, kslow, leading to
adduct 3 was small at low sulphite concentrations,
ꢃ0.007 mol dm 3, so that values of kslow were unreliable.
is interesting that the values of K2 for formation of
adducts 3 are considerably higher for the alkyl deriva-
tives 3a and 3b than for the phenyl derivatives 3c and 3d.
The K1 values provide no evidence that the phenyl
derivatives are sterically disadvantaged relative to the
ethyl derivatives. It has been argued that in related
systems solvation is of prime importance in determining
adduct stability.5 In the 1:2 adducts 3 which carry four
negative charges, solvation by the largely aqueous
medium will be very important. The presence of
hydrophobic groups will reduce such solvation. Thus it
is likely that the lower stabilities of the phenyl derivatives
than of their alkyl counterparts may result from greater
inhibition of hydration of the ionic groups.
RELATIVE STABILITIES OF s-ADDUCTS
Rate and equilibrium constants are collected in Table 5.
The values of K1, the equilibrium constant relating to
sulphite attack at the unsubstituted 3-position, decrease in
the order of 1-substituent OPh > SPh ꢁ SEt > OEt.
Steric as well as electronic effects are expected to be
important.1,2 It is known that the presence of a bulky
substituent at the 1-position may result in rotation from
the ring plane of the nitro groups at the 2- and 6-positions,
reducing their electron-withdrawing capacity. The in-
ductive effect of the 1-substituents at the 3-position may
be judged by smeta values. The values for OPh and OEt
groups are reported as 0.25 and 0.10 respectively.16,17
Values for SPh and SEt groups are not available, but the
value for the SMe group is 0.15. A similar value is
expected for the SEt group, with a larger value for SPh. It
seems that the K1 values largely reflect the inductive
effects of the 1-substituents. For comparison, values of
NUCLEOPHILIC SUBSTITUTION
A major difference between the phenyl, 1c and 1d, and
alkyl, 1a and 1b, derivatives is in the rate of displacement
of the 1-substituent. With the former, substitution was
found to occur relatively rapidly, whereas with the latter
there was no observable reaction after 1 h. One factor
contributing to this difference will be the higher
stabilities of the 1:2 adducts 3 formed from the alkyl
derivatives, resulting in lower equilibrium concentrations
of the substrates. However, the major factor is the
enhanced leaving group ability of phenoxide and phenyl
sulphide compared with ethoxide and ethyl sulphide.12,13
1
K1 for sulphite attack in 100% water are 290 dm3 mol
for 1,3,5-trinitrobenzene4 and 140 dm3 mol 1 for methyl
2,4,6-trinitrophenyl ether.6 The presence of 20% DMSO
in our systems is expected1,2 to result in increased
stabilities of the 1:1 adducts.
Our results, kinetic and spectroscopic, provide no
evidence for cis–trans isomerism in the 1:2 adducts. It is
likely that, as in related systems,6 the trans isomers are
favoured. Here the added sulphite groups are on opposite
faces of the ring, minimizing unfavourable interactions. It
Thus it is known12 that phenoxide departure is 106 times
faster than methoxide departure from the adduct 5. The
likely effect of this difference is shown in a schematic
energy level diagram in Fig. 1. Although substitution will
involve the intermediates 6, there is no evidence, either
spectroscopic or kinetic, for the accumulation of such
intermediates, and the inference is that they have lower
1998 John Wiley & Sons, Ltd.
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, VOL. 11, 787–792 (1998)

REACTIONS OF SULPHITE IONS WITH ETHERS AND THIOETHERS
791
Figure 1. Suggested schematic potential energy pro®le for reaction of 1 with sulphite
thermodynamic stabilities than their isomers 2 formed by
addition at the unsubstituted 3-position. The data in Table
5 allow the comparison of values of rate constants for
attack at unsubstituted (k1) and substituted (k3) ring
positions. The ratios are 250 in the case of 1c and 34 for
1d. The slower attack at the substituted positions is likely
to derive from F-strain18 associated with the proximity of
two bulky groups. Inhibition of hydration of the adding
sulphite ion by the presence of the 1-substituent may also
be a factor. The kinetic and thermodynamic preference
for attack at the 3-position may be described as K3T3 in
Buncel’s nomenclature.19,20
adducts 6c and 6d. The results suggest a leaving group
order in these systems of PhO , PhS > SO32- > EtO ,
EtS .
EXPERIMENTAL
Compounds 1a, 1c and 1d were available from previous
work.17 Compound 1b was prepared by reaction in
ethanol of picryl chloride with one equivalent of ethane
thiol in the presence of sodium ethanoate. Recrystalliza-
tion from methanol yielded yellow crystals, m.p. 44°C
(lit. 45°C21). Sodium sulphite, sodium sulphate and
DMSO were the purest grades commercially available.
Distilled water was boiled to remove carbon dioxide and
subsequently protected from the atmosphere. NMR
spectra were recorded using a Varian VXR-400 spectro-
meter with D2O and [2H6] DMSO as solvent. UV/vis
spectra and kinetic measurements were made with a
Perkin-Elmer Lambda 12 spectrometer or with an
Applied Photophysics SX-17 MV stopped-flow spectro-
meter. Reported rate constants are the means of several
determinations and are precise to Æ5%. To check that no
depletion of sulphite concentration occurred by reaction
with acidic impurities in the solvent, measurements were
made both in the presence and absence of borax buffers
(pH 9); no differences in rate constants were observed
between buffered and unbuffered solutions.
In view of the excellent leaving group abilities of
phenoxide and phenyl sulphide, it is likely that
nucleophilic attack by sulphite will be rate-limiting in
the overall substitution process. Hence intermediates 6c
and 6d, once formed, will rapidly yield the substitution
product. The contrastingly slow substitution in the ethyl
derivatives is likely to derive from a change in the rate-
determining step so that cleavage of the leaving group
becomes rate-limiting. It is worth noting that in the
substitution reactions of 1a–1d with hydroxide ions to
produce picric acid, where nucelophilic attack is rate-
limiting, the alkyl and phenyl derivatives react at very
similar rates.17 Hence it is to be expected that the values
of k3 for attack of sulphite at the 1-position of 1a and 1b
will be similar to those observed for 1c and 1d. The slow
substitution in the ethyl derivatives derives from the poor
leaving group abilities of ethoxide and ethyl sulphide
coupled with the low thermodynamic stabilities of the
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