Solvent network at the transition state in the solvolysis of hindered sulfonyl compounds

Article abstract of DOI:10.1002/poc.3588

Alcoholysis rates of unhindered benzenesulfonyl chlorides (X-ArSO₂Cl, X = H-; 4-Br-; 4-Me-) are similar in methanol; the same behavior is also observed in ethanol, whereas the reactivity order in iso-propanol is 4 Me- < H- < 4-Br-. On the other hand, alcoholysis of sterically hindered arenesulfonyl chlorides (X-ArSO₂Cl) (X = 2,4,6-Me₃-3-NO₂-; 2,6-Me₂-4-tBu-; 2,4,6-Me₃-; 2,3,5,6-Me₄-; 2,4,6-iPr₃-; 2,4-Me₂-; 2,4,6-(OMe)₃-) in all studied alcohols show a significant increase in reactivity, the so-called positive steric effect. Most of the substrates showed a reaction order b ~ 2 with respect to the nucleophile in methanol and ethanol, and b ~ 3 in iso-propanol. The correlation between reactivity and the Kirkwood function (1/ξ) gives negative sensitivity (U) for all systems. All substrates showed high sensitivity to media nucleophilicity that depends on Σσ_X. Obtained results suggest the alcoholysis of benzenesulfonyl chlorides proceeds through S_N2 mechanism where the transition state (TS) involves the participation of 2–3 alcohol molecules; such a TS can be cyclic, in the case of unbranched alcohols, or linear, for alcohols with bulkier hydrocarbon groups like iso-propanol. To include the number of alcohol molecules playing such a role in the TS, the following terminology is proposed: cS_N2s_n for S_N2 reactions involving n solvent molecules in a cyclic (c) TS, where “s” stands for the solvent and “n” is either the closest integer or half-integer to the reaction order relative to the solvent or, in computational studies, the proposed number of solvent molecules taking part in the TS, whereas S_N2s_n is proposed when the TS is not cyclic. Copyright

Full text of DOI:10.1002/poc.3588

Research article
Received: 19 February 2016,
Revised: 25 April 2016,
Accepted: 27 April 2016,
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/poc.3588
Solvent network at the transition state in the
solvolysis of hindered sulfonyl compounds
Mykyta Iazykova,b*, Ludmila Rublovaa, Moisés Canle L.b and
J. Arturo Santaballab
Alcoholysis rates of unhindered benzenesulfonyl chlorides (X-ArSO2Cl, X = H-; 4-Br-; 4-Me-) are similar in methanol; the same
behavior is also observed in ethanol, whereas the reactivity order in iso-propanol is 4 Me- < H- < 4-Br-. On the other hand,
alcoholysis of sterically hindered arenesulfonyl chlorides (X-ArSO2Cl) (X = 2,4,6-Me3-3-NO2-; 2,6-Me2-4-tBu-; 2,4,6-Me3-;
2,3,5,6-Me4-; 2,4,6-iPr3-; 2,4-Me2-; 2,4,6-(OMe)3-) in all studied alcohols show a significant increase in reactivity, the so-
called positive steric effect.
Most of the substrates showed a reaction order b ~ 2 with respect to the nucleophile in methanol and ethanol, and b ~ 3 in
iso-propanol. The correlation between reactivity and the Kirkwood function (1/ξ) gives negative sensitivity (U) for all systems.
All substrates showed high sensitivity to media nucleophilicity that depends on ΣσX.
Obtained results suggest the alcoholysis of benzenesulfonyl chlorides proceeds through SN2 mechanism where the
transition state (TS) involves the participation of 2–3 alcohol molecules; such a TS can be cyclic, in the case of unbranched
alcohols, or linear, for alcohols with bulkier hydrocarbon groups like iso-propanol. To include the number of alcohol
molecules playing such a role in the TS, the following terminology is proposed: cSN2sn for SN2 reactions involving n solvent
molecules in a cyclic (c) TS, where “s” stands for the solvent and “n” is either the closest integer or half-integer to the reaction
order relative to the solvent or, in computational studies, the proposed number of solvent molecules taking part in the TS,
whereas SN2sn is proposed when the TS is not cyclic. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords: alcoholysis; cSN2sn; kirkwood function; media nucleophilicity; nucleophilic substitution; reaction mechanisms; SN2
mechanism; SN2sn; solvent networks; solvolysis; sulfonyl chlorides
those
for
undeuterated
2,4,6-trimethylbenzenesulfonyl
INTRODUCTION
chloride, such evidence lets us neglect σ-π-hyperconjugation
as a possible reason of the “positive steric effect” in this
particular case.[10,28] The observation of small kinetic solvent
isotope effects is an evidence against the catalytic effect of a
second nucleophile molecule present in the TS[4,5,11] and
supports the participation of a network of alcohol molecules
in the TS, even as a cyclic chain.[28]
Here, we present a mechanistic study of the alcoholysis (Scheme 1)
of different sterically hindered arenesulfonyl chlorides (X-ArSO2Cl) at
323 K (X = 2,4,6-Me3-3-NO2-; 2,6-Me2-4tBu-; 2,4,6-Me3-; 2,3,5,6-Me4-;
2,4,6-iPr3-; 2,4-Me2-; 2,4,6-(OMe)3-; H-; 4-Me-; 4-Br-) in methanol, eth-
anol, and iso-propanol to elucidate the structure of the TS and
looking for a better understanding of the solvolytic process.
Nucleophilic substitution at sulfur of the sulfonyl group has
been
a
frequent matter of debate[1–5] because of the
ambiguity of the solvolysis mechanism, often considered as
bimolecular, with different transition state (TS) symmetries,[6,7]
involving catalytic assistance of the solvent,[4,5,8,9] a possible
molecular rearrangement during the nucleophilic attack,[10]
and so on. A number of common mechanistic criteria for
solvolytic processes of arenesulfonyl chlorides points to a
typical SN2-nucleophilic substitution mechanism: similar
secondary and solvent isotope effect,[11,12] effect of the change
of nucleophile,[3,13,14] and solvent effect.[3,14,15]
In recent years, the problem became more complicated
with the study of sterically hindered arenesulfonyl
compounds in which the attack on the S atom is apparently
inhibited by the presence of ortho-alkyl groups.[16] On the
other hand, hindered structures based on derivatives of
benzene sulfonyl chloride have shown a significant increase
in reactivity, the so-called positive steric effect,[6,16] which is
in disagreement with the classical interpretation of the
electronic effect of substituents on the rate of SN2
processes.[10,13,15,17–19] Based on the described observations,
and others already available in the literature, deviations of
the TS structure are expected for a number of hindered
substrates.[1,2,4,5,17,18,20–27]
* Correspondence to: Mykyta Iazykov, Chemical Reactivity and Photoreactivity
Group, Department of Physical Chemistry and Chemical Engineering, Faculty
of Sciences and CICA, University of A Coruña, E-15071 A Coruña, Spain.
E-mail: nikitich205@gmail.com
a M. Iazykov, L. Rublova
Department of General Chemistry, Faculty of Ecology and Chemical
Technology, Donetsk National Technical University, ave Bogdana
Khmelnitskogo 106, 83015, Donetsk, Ukraine
b M. Iazykov, M. Canle L., J. A. Santaballa
When
studying
the
alcoholysis
of
deuterated
Chemical Reactivity and Photoreactivity Group, Department of Physical
Chemistry and Chemical Engineering, Faculty of Sciences and CICA, University
of A Coruña, E-15071, A Coruña, Spain
2,4,6-trimethylbenzenesulfonyl chloride,[28] we obtained
kinetic data and activation parameters comparable with
J. Phys. Org. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.

M. IAZYKOV ET AL.
propanolysis (Fig. 3), the tendency is less clear.
Here, in contrast with the similar reactivity in
methanolysis and ethanolysis, the reactivity
order within the model series is 4-Me- < H- <
4-Br-. Different correlations might be possible
for different combinations of hindered and
unhindered substrates; therefore, we have
Scheme 1. Classical SN2 mechanism in the alcoholysis of arenesulfonyl chlorides
not drawn any tendency line, but just keep a qualitative analysis.
The tendency shown in Figs. 1 and 2 implies a non-negligible
decrease in electron density at the reaction site. This may be
indicative of a “loosening” of the S-Cl bond and subsequent
displacement of the TS toward a more “cationic”-like TS
structure.[30]
2,4-Me2-benzenesulfonyl chloride shows higher reactivity than
the model series, lesser in iso-propanol than in unbranched
alcohols (Figs. 1–3).
RESULTS AND DISCUSSION
First-order kinetic model adequately fits to chemical kinetic data
of alcoholysis. Reaction rates are scarcely affected in the case of
unhindered benzenesulfonyl chlorides (X-ArSO2Cl, X = H-; 4-Br-;
4-Me-) when solvolysis takes place in methanol and ethanol as
shown in Figs. 1 and 2. Hereafter we will call those three
compounds “model series”, and the term “hindered” will refer
to the presence of two alkyl ortho substituents.
Hammett plots for methanolysis and ethanolysis (Figs. 1 and 2),
with all the difficulties derived from assigning values to the
effects of substituents in different positions,[29] show a general
tendency to an increased reactivity as the combination of
substituent’s effects becomes more electron releasing. For iso-
Sulfonyl chlorides X-ArSO2Cl with methyl/methoxy substitu-
ents in both ortho- positions (X = 2,4,6-Me3-, 2,6-Me2,4-t-Bu-;
2,3,5,6-Me4-; 2,4,6-Me3,3-NO2-; 2,4,6-OMe3-,) show a noticeable
higher reactivity for all the three alcohols (Figs. 1–3). The acceler-
ating effect of alkyl ortho substituents also operates with the
bulkier compound 2,4,6-i-Pr3-benzenesulfonyl chloride; it reacts
faster than model series and 2,4-Me2-benzenesulfonyl chloride
in methanol and ethanol.
Correlation between reactivity and the Kirkwood function
(1/ξ) takes into account exclusively nonspecific solvation, that
is, the ability of the solvent to promote charge transfer, as
well as to polarize substrate molecules.[31] The permittivity of
the mixture (ξmix
)
was calculated according to the
Lichtenecker–Rother Eqn 1,:[32]
log ξ mix ¼ falcꢀ log ξ alc þ fhexꢀ log ξ hex
;
(1)
where falc and fhex are the volume fractions, and ξalc and ξhex
are the permittivities of alcohol and hexane, respectively.
Equation 2 was used to build the corresponding correlations:
1
ξ
log kobs ¼ U þ logk0:
(2)
When solvent polarity is considered, the sensitivity (U) is
negative for all systems (Table 1).
Figure 1. Hammett plot for X-ArSO2Cl methanolysis (T = 323 K): ●, un-
hindered compounds; ○, compounds with enhanced reactivity
Figure 2. Hammett plot for X-ArSO2Cl ethanolysis (T = 323 K): ●, unhin-
dered compounds; ○, compounds with enhanced reactivity
Figure 3. Hammett plot for X-ArSO2Cl iso-propanolysis (T = 323 K): ●,
unhindered compounds; ○, compounds with enhanced reactivity
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SOLVENT AT THE TS IN THE SOLVOLYSIS OF HINDERED SULFONYL COMPOUNDS
Table 1. Fitted parameters for log kobs versus 1/ξ dependences (Eqn 2) for X-ArSO2Cl solvolysis
in alcohol-hexane (43–100% MeOH, 36–100% EtOH, 29–100% i-PrOH; V/V) mixtures at 323 K
X
Alcohol
log k0
U
R2
n*
2,4,6-Me3-3-NO2-
MeOH
EtOH
i-PrOH
MeOH
EtOH
i-PrOH
MeOH
EtOH
i-PrOH
MeOH
EtOH
i-PrOH
MeOH
EtOH
i-PrOH
MeOH
EtOH
i-PrOH
MeOH
EtOH
i-PrOH
MeOH
EtOH
ꢂ2.86 0.03
ꢂ3.32 0.05
ꢂ3.68 0.05
ꢂ2.50 0.04
ꢂ3.04 0.05
ꢂ3.77 0.06
ꢂ2.45 0.04
ꢂ3.07 0.03
ꢂ3.70 0.02
ꢂ2.63 0.05
ꢂ3.23 0.04
ꢂ3.92 0.04
ꢂ2.89 0.03
ꢂ3.59 0.01
ꢂ4.62 0.06
ꢂ3.12 0.03
ꢂ3.64 0.01
ꢂ4.29 0.05
ꢂ2.14 0.04
ꢂ3.13 0.02
ꢂ3.72 0.08
ꢂ3.31 0.02
ꢂ3.82 0.05
ꢂ4.50 0.04
ꢂ3.32 0.05
ꢂ3.89 0.06
ꢂ4.51 0.03
ꢂ3.48 0.02
ꢂ3.83 0.04
ꢂ4.16 0.04
ꢂ2.7 0.2
ꢂ3.2 0.3
ꢂ6.1 0.4
ꢂ3.2 0.3
ꢂ3.7 0.3
ꢂ5.9 0.5
ꢂ3.5 0.3
ꢂ3.4 0.2
ꢂ6.9 0.1
ꢂ3.1 0.4
ꢂ3.6 0.2
ꢂ5.8 0.3
ꢂ5.1 0.3
ꢂ4.6 0.1
ꢂ5.4 0.4
ꢂ3.0 0.2
ꢂ4.0 0.1
ꢂ6.2 0.4
ꢂ2.3 0.4
ꢂ1.9 0.1
ꢂ5.0 0.6
ꢂ2.6 0.1
ꢂ3.2 0.3
ꢂ4.7 0.3
ꢂ2.5 0.3
ꢂ3.0 0.4
ꢂ4.8 0.2
ꢂ3.1 0.1
ꢂ2.6 0.2
ꢂ5.8 0.3
0.988
0.982
0.989
0.978
0.985
0.982
0.981
0.994
0.999
0.962
0.988
0.993
0.994
0.999
0.982
0.986
0.999
0.989
0.956
0.992
0.957
0.995
0.977
0.990
0.953
0.962
0.996
0.994
0.980
0.991
5
4
5
5
5
5
4
5
5
5
5
5
4
4
5
5
3
5
4
4
5
5
4
5
5
4
4
5
5
5
2,6-Me2-4-t-Bu-
2,4,6-Me3-
2,3,5,6-Me4-
2,4,6-i-Pr3-
2,4-Me2-
2,4,6-(OMe)3-
H-
i-PrOH
MeOH
EtOH
i-PrOH
MeOH
EtOH
4-Me-
4-Br-
i-PrOH
*n, sample size.
For methanol-hexane and ethanol-hexane mixtures, U values
are closer and even approximately the same (Table 1), while they
almost doubles for iso-propanol-hexane mixtures. It is also
remarkable that U grows inversely with the polarity of the
alcohol, in accordance with the Reactivity Selectivity Principle,[33]
and according to Hughes–Ingold rule;[31] increase in reactivity
with solvent polarity indicates the TS is more solvated than the
reactants. From these results, it follows that the TS’s for
methanolysis and ethanolysis of sulfonyl chlorides are similar
and much less polar than for iso-propanolysis, which is in
agreement with the observed reactivity tendency. Thus, more
polar TS’s occur in less polar media, with decrease of reactivity.
Such tendency is quite unusual for SN2 processes. The different
behavior of iso-propanolysis cannot be explained by the
difference in media polarity because the experiments were
carried out in media of similar polarity.
unhindered benzenesulfonyl chloride. In contrast with Bentley’s
results,[27] sensitivity coefficients increase as ΣσX decreases, which
may be explained by the different nucleophile type (97% TFE and
40% ethanol) used by him and the corresponding polarities.
The high sensitivity coefficients to solvent nucleophility for
hindered arenesulfonyl chlorides once again suggests an SN2-
like mechanism.
Effective rate constants of solvolysis, kobs, were determined by
varying the nucleophile (alcohol) concentration, CN, using
constant initial concentration of sulfonyl chloride in alcohol-
hexane mixtures at 323 K (Supporting Information). Alcoholysis
rate varies linearly with alcohol concentration (Fig. 4). When a
specific sulfonyl chloride is considered, the reaction rate varies
in the order: methanolysis > ethanolysis > iso-propanolysis. The
presence of ortho-methyl groups accelerates the process in
agreement with earlier observations.[3–5,16,19,28,34]
Kinetic data allow us to compare the reactivity of
arenesulfonyl chlorides in different media of equal polarity
(εmix ≈ 10) that simultaneously vary by the nucleophile type
The slope, b, of the observed dependences gives the reaction
order with respect to the nucleophile, that is, the corresponding
reaction order, according to Eqn 3:[21]
(MeOH, EtOH, and i-PrOH). The ratios of rate constants kMeOH
/
k
EtOH, kMeOH/ki-PrOH, and kEtOH /ki-PrOH measure the sensitivity of
lnkobs ¼ A þ bꢁ ln CN
(3)
the X-substituted substrate to the nucleophilicity of medium.
The obtained results show higher sensitivity coefficients for all
sterically hindered substrates with ΣσX < 0 (Table 2) relative to
The so-obtained reaction orders are compiled in Table 3 (see
also Tables S9, S11, and S13 at the Supporting Information).
J. Phys. Org. Chem. (2016)
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M. IAZYKOV ET AL.
Table 2. Observed rate constants and their ratios for solvolysis of X-ArSO2Cl in MeOH-hexane, EtOH-
hexane, and i-PrOH-hexane mixtures at 323 K
MeOH·104, sꢂ1
Mix = 9.4
kEtOH·104, sꢂ1
Mix = 10.0
k
i-PrOH·104, sꢂ1
Mix = 9.8
kMeOH
kEtOH
kMeOH
kiꢂPrOH
kEtOH
kiꢂPrOH
X
k
ε
ε
ε
2,4,6-Me3-3-NO2-
2,6-Me2-4-t-Bu-
2,4,6-Me3-
2,3,5,6-Me4-
2,4,6-i-Pr3-
2,4-Me2-
2,4,6-(OMe)3-
H-
4-Me-
7.27 0.01
13.6 0.1
14.8 0.1
11.0 0.1
3.48 0.01
3.45 0.01
40.8 0.01
2.55 0.01
2.56 0.01
2.14 0.01
2.37 0.01
4.11 0.01
4.06 0.01
0.466 0.001
0.374 0.001
0.416 0.001
0.315 0.001
0.072 0.001
0.125 0.001
0.517 0.001
0.102 0.001
0.104 0.001
0.174 0.001
3.06
3.31
3.65
4.02
3.89
3.69
8.51
3.37
3.80
2.46
15.6
36.4
35.7
34.9
48.4
27.6
78.9
25.1
24.6
12.3
5.10
11.0
9.77
8.68
12.4
7.47
9.27
7.46
6.46
5.00
2.74 0.01
0.895 0.001
0.933 0.01
4.79 0.01
0.757 0.001
0.673 0.001
0.872 0.001
4-Br-
Solvolysis in ethanol (Fig. 5) shows reaction orders 2 < b < 3
with respect to the nucleophile (ethanol) for all ortho-methylated
substrates (1–4 and 7 in Table 3, see also Table S11 in the
Supporting Information). Unhindered substrates (8 and 10 in
Table 3) show b ~ 2, but 4-Me-benzenesulfonyl chloride (9)
(b ~ 2,8). 2,4,6-iPr3-benzenesulfonyl chloride (5) and 2,4,6-(OMe)
3-benzenesulfonyl chloride (6) (Table 3) also have a particular be-
havior, as for methanolysis, with slope 3.0 and 1.5, respectively.
In the case of iso-propanolysis (Fig. 6), the reaction order with
respect to the nucleophile (iso-propanol) is ~ 3, except for
2,4,6-(OMe)3-benzenesulfonyl chloride (6) and benzenesulfonyl
chloride (8) for which is slightly higher than 2 (Table 3; see also
Table S13 at the Supporting Information).
The reactivity of sulfonyl chlorides significantly depends on
the nucleophile concentration (Figs. 4–6), as predicted for SN2
processes.[1–7] Assuming the reaction order on the nucleophile
relates to the number of solvent molecules participating in the
TS, our results suggest the TS involves two nucleophile mole-
cules in methanolysis and three for iso-propanolysis (Table 3).
The change in space requirements at the TS as the steric hin-
drance of the nucleophile increases may explain the increase in
the number of nucleophile molecules for iso-propanolysis TS.
The intermediate values obtained for ethanolysis can be
Figure 4. log kobs vs. log CN for X-ArSO2Cl methanolysis in methanol-
hexane (43–100%, V/V), T = 323 K
Sterically unhindered substrates (8–10, Table 3, see also Table
S9 at the Supporting information) and also all hindered ortho-
methylated compounds showed a reaction order b ~ 2 with
respect to the nucleophile (methanol) but 2,4,6-iPr3-
benzenesulfonyl chloride (5) and 2,4,6-(OMe)3-benzenesulfonyl
chloride (6) (Table 3), for which reaction orders are 3 and 1.3,
respectively.
Table 3. Reaction order relative to the nucleophile, b of Eqn 3, for X-ArSO2Cl solvolysis in alcohol-hex-
ane mixtures, T = 323 K
№
X
Reaction order relative to the nucleophile (b of Eqn 3)
MeOH-hexane
EtOH-hexane
Iso-propanol-hexane
43–100%, V/V
36–100%, V/V
29–100%, V/V
1
2
3
4
5
6
7
8
2,4,6-Me3-3-NO2-
2,3,5,6-Me4-
2,4,6-Me3-
2,6-Me2-4tBu-
2,4,6-i-Pr3-
2,4,6-(OMe)3-
2,4 Me2-
H-
4-Me-
4-Br-
2.3 0.2
2.0 0.2
2.1 0.1
2.1 0.1
3.1 0.1
1.31 0.05
1.95 0.07
2.1 0.1
1.90 0.06
2.0 0.1
2.3 0.1
2.8 0.1
2.66 0.03
2.6 0.1
3.04 0.04
1.52 0.09
2.65 0.08
2.1 0.2
3.2 0.1
3.04 0.08
3.0 0.2
3.2 0.2
3.0 0.2
2.25 0.05
3.5 0.2
2.35 0.08
3.1 0.1
9
10
2.8 0.2
2.01 0.04
3.3 0.2
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SOLVENT AT THE TS IN THE SOLVOLYSIS OF HINDERED SULFONYL COMPOUNDS
Figure 5. log kobs versus log CN for X-ArSO2Cl ethanolysis in ethanol-hex-
ane (36–100%, V/V), T = 323 K
Figure 7. Reaction order with respect to the nucleophile (b) versus
Charton’s ν for X-ArSO2Cl solvolysis
Table 4. Fitted parameters of Eqn 4 for X-ArSO2Cl solvolysis
in iso-propanol-hexane system at T = 323 K
X
b = δ ꢁ ν + c1
c1
δ
R2
2,6-Me2-4tBu-
2,4,6-Me3-
2,3,5,6-Me4-
2,4 Me2-
1.56 0.03
1.62 0.07
1.34 0.07
1.3 0.3
0.97 0.02
0.90 0.06
1.24 0.06
1.5 0.2
0.999
0.996
0.997
0.977
0.964
4-Me-
1.3 0.3
1.2 0.2
Figure 6. log kobs versus log CN for the iso-propanolysis of XArSO2Cl in
iso-propanol-hexane (29–100%, V/V), T = 323 K
because of higher steric requirements of the TSs, where all
the studied substrates (ΣσX < 0 and ΣσX > 0) show a reaction
order, relative to the nucleophile, higher than one. However,
the importance of electronic effects should not be neglected,
despite the poor sensitivity shown by all systems.
interpreted in terms of a change in the degree of solvation and
the simultaneous participation of an alcohol molecule in interac-
tions with other substrate and solvent molecules.
From our point of view in going to bulkier nucleophiles, the
role of steric effects in TS increases including the positive steric
effect, which is reflected on the specific kinetic behavior of hin-
dered sulfonyl chlorides.
Obviously, TS space requirements must change with the
length/size of the side chain of the alcohol. The reaction order
with respect to the nucleophile, b, was plotted versus Charton’s
steric constants ν to estimate the steric effect of the alcohol
(Fig. 7).[35] Most of the substrates show an increase in b with
bulkier nucleophiles. Satisfactory correlations were obtained
only for alkylated derivatives of benzenesulfonyl chloride with
ΣσX < 0 (Table 4) in terms of the linear equation:
Space requirements are also supported by X-ray diffraction
data. The highly sterically hindered 2,4,6-iPr3-benzenesulfonyl
chloride[36] shows a slightly distorted benzene ring plane
( 0.021 Å), which takes the form of a highly flattened “bath”.
Moreover, the relative orientation of the ortho-iso-propyl
substituents facilitates intramolecular interaction between the
oxygen atoms of the sulfo group and the hydrogens of the
central carbon atoms of the iso-propyl ortho-groups (Fig. 8).
Thus, bulky iso-propyl ortho-substituents impede the rotation
around the C-S bond, limiting the approach of the nucleophile,
which contributes to the formation of a TS with three solvent
molecules. 2,4,6-(OMe)3-benzenesulfonyl chloride exhibits
lower reaction order with respect to the nucleophile but an
increased reactivity, providing additional evidence that SN2-
type substitution at tetracoordinate hexavalent sulfur atom in
arenesulfonic acids derivatives show an important variability
of the TS structure.
Obtained results suggest the TS incorporates 2–3 alcohol mol-
ecules, possibly forming a cyclic solvent network, as shown in
Scheme 2. Within this framework, the reaction proceeds as fol-
lows: (i) the sulfonyl chloride is attacked by an alcohol molecule
linked to other alcohol molecules associated by hydrogen bonds;
(ii) a cyclic TS is formed, with the charge redistributed along the
whole network of forming/breaking bonds; and (iii) the
nucleofuge leaves and the cyclic TS collapses. The main benefit
of a cyclic TS is the extra stabilization obtained by charge
b ¼ δꢁν þ c1
(4)
From there it follows that the reaction order with respect to
the nucleophile, b, increases with the volume of alkyl ortho sub-
stituents and is not related uniquely to the electronic nature of
the X substituent group.
Recently, Yamabe et al. carried out a computational chem-
istry study of the hydrolysis of benzenesulfonyl chlorides
using DFT, with explicit consideration of water molecules.[8]
They assume a mechanistic change from SN2 to SN3 on going
from electron donor to electron withdrawing substituents.
This would probably not be the case in alcoholic solutions,
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M. IAZYKOV ET AL.
Scheme 3. Cyclic transition state of sterically hindered 2,4,6-
trimethylbenzenesulfonyl chloride involving two methanol molecules
(cSN2s2)
SN2-like mechanism in which one molecule is playing the role of
a general base catalyst (Scheme 2b).[5,9,18]
Depending on the number of solvent molecules involved in
the solvent network, it should be renamed cyclic-SN2sn (or
cSN2sn) (Scheme 2a), where “s” stands for the solvent and “n”
would be the number of solvent molecules involved, or simply
SN2sn, (Scheme 2b). For “n,” it is suggested either the closest
integer or half-integer to the reaction order relative to the
solvent or the proposed number of solvent molecules taking part
in the TS in computational studies.
Figure 8. X-Ray diffraction structure of 2,4,6-tri(propan-2-yl)
benzenesulfonyl chloride
The “positive” ortho-effect can be explained through the
spatial requirements of the TS: ortho-alkyl groups limit free
rotation around the C-S bond of the sulfonyl chloride,[11,36–39]
leaving the S in a position that favors the formation of cyclic TS
(Scheme 3). TS of unhindered substrates, although having less
steric constraints, can also be cyclic.
Considering the results presented in this paper, the alcoholysis
of sterically hindered ortho-alkyl arenesulfonyl chlorides
(X-ArSO2Cl) proceeds through an SN2-nucleophilic substitution
mechanism involving a network, cyclic or open, of alcohol
molecules, the structure of the TS being mostly determined by
solvation interactions. A notation is proposed to inform about
solvent molecules playing a role in the TS, thus avoiding the
controversial mechanistic notation SN3.
Scheme 2. TS involving three alcohol molecules. a. cSN2s3 TS; b. SN2s3 TS
dispersion and that proton transfer along the network is not
necessarily the rate-limiting step. Such cyclic TS would contain
at least three molecules, four in some cases, thus explaining
the reaction order obtained with respect to alcohol (2–3). This
kind of TS can be considered as the boundary between tri-
molecular and bi-molecular processes, although formally it
would correspond to an SN2-process.
The influence of the electron nature of the substituent X on
the TS and, therefore, on the reactivity is unambiguous.
Electron-withdrawing substituents contribute to the bond-
forming interaction S···O, while electron-donating substituents
reduce the positive charge density on the sulfur thereby
preventing it. On the other hand, electron-donating substitu-
ents facilitate the nucleofuge departure, increasing the
negative charge density at the Cl (|δ-| ↑), which also promotes
the Cl- - -H hydrogen bond formation that helps forming the
cyclic TS. Electron-withdrawing substituents reduce the relative
negative charge density on the Cl (|δ-| ↓), which make difficult
the formation of the Cl- - -H bond. From this point of view, the
reason for the very similar rates of alcoholysis observed for
benzenesulfonyl chloride and 4-Me-benzenesulfonyl chloride
becomes clear: methyl group promotes stabilization of the
cycle and eliminates its negative impact on S···O bond-
CONCLUSIONS
Mechanistic details and features of the TS for solvolytic processes
at the sulfonyl sulfur have been discussed. The existence of
different possible kinds of TS for the SN2 substitution is assumed
and described.
The sensitivity to media polarity U growing inversely with
the polarity of the alcohol indicates the TS is more solvated
than the reactants. The TS’s for methanolysis and ethanolysis
of sulfonyl chlorides are similar, and much less polar than for
iso-propanolysis. Most of substrates showed a reaction order
b ~ 2 with respect to the nucleophile (methanol and ethanol)
and b ~ 3 in iso-propanol. The reaction order with respect to
the nucleophile, b, increases with the volume of nucleophile
(alcohol) and is not related uniquely to the electronic nature
of the X substituent group. The higher sensitivity to nucleophi-
licity of medium for all substrates points to the bimolecular
SN2-like mechanism. We propose that cyclic polymolecular
TSs can take place. The electronic nature of the benzene ring
substituent and the interactions of the sulfonyl group with
ortho-alkyl substituents explain the significant difference in
the reactivity of substrates with different structures within
the same mechanism of solvolysis. The structure and
forming, and as
a consequence, the reactivity remains
practically unchanged.
Likely, the reason for the observed variability in TS is the large
steric hindrance of bulky iso-propyl groups that prevents the
formation of cyclic TS. The high reaction order on the
nucleophile (b ~ 3) in iso-propanol points to a TS involving three
alcohol molecules, that could also be described according to an
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J. Phys. Org. Chem. (2016)

SOLVENT AT THE TS IN THE SOLVOLYSIS OF HINDERED SULFONYL COMPOUNDS
molecularity of TS with nucleophilic assistance of solvent
depends strongly on the structure of nucleophile. The TS can
Acknowledgements
The authors gratefully acknowledge EU financial support for the
mobility of MI to the UDC within the trans-European mobility
Erasmus Mundus action TEMPO (372283-1-2012-1-PT-ERA
MUNDUS-EMA21).
be cyclic for unbranched alcohols (methanol, ethanol) or linear
(SN3-like mechanism) for alcohols with bulky alkyl groups
(iso-propanol). In the case of 2,4,6-i-Pr3-benzenesulfonyl
chloride, a large steric volume of o-alkyl groups promotes
the formation of linear TS of SN3-type that facilities the
removal of steric hindrance to the nucleophile attack, which
is reflected on its reactivity.
Our recent studies have shown that arenesulfonyl chlorides
alcoholysis takes place through a spectrum of SN2 TSs of cyclic
or linear structure with participation of a network of additional
solvent molecules, mimicking a general base catalysis process.
cSN2sn or SN2sn notations are proposed to represent solvolytic
processes undergoing bimolecular nucleophilic substitutions
involving solvent molecules at the TS, cylic (c) or linear. “n” is
either the closest integer or half-integer to the reaction order
relative to the solvent or, in computational studies, the proposed
number of solvent molecules taking part in the TS.
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SUPPORTING INFORMATION
Additional supporting information can be found in the online
version of this article at the publisher’s website.
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