it will go across the line A, calculated from eqn. 4, at pKLG
=
with a Varian Gemini 200 spectrometer (200 MHz) with TMS
10.8 which is, therefore, the break-point (indicated by the solid
arrow in Fig. 2). This implies that the change in mechanism,
within this series, would be experimentally inaccessible since
substituted phenols having a pKa greater than 10.8 are not
common. Resorting to poorer leaving groups, such as alkoxides,
will not be useful since sulfonate esters of aliphatic alcohols
usually react with C᎐O fission.13
as internal standard and [2H6]acetone or CDCl3 as solvent.
Synthesis
General procedure for the synthesis of the esters. 2,6-Dimethyl-
phenol was sulfonated with concentrated sulfuric acid at 100 ЊC
for 6 h. After cooling to 0 ЊC the reaction mixture was poured
into brine and the sodium salt of the 3,5-dimethyl-4-hydroxy-
benzenesulfonic acid was collected by filtration, dried and
treated with acetic anhydride and pyridine at room temper-
ature overnight. The resulting pyridinium salt of the acetyl
derivative was triturated, after removal of the excess of acetic
anhydride and pyridine, with an excess of solid PCl5 and
finally poured into ice–water. The acetylated sulfonyl chloride
was filtered, dried and treated with equimolar amounts of
the appropriate substituted phenol and triethylamine in
anhydrous methylene chloride for several hours at room tem-
perature. After usual work-up of the reaction, the ester was
deacetylated by refluxing it for 30 min under nitrogen in a
solution of dry hydrochloric acid in absolute ethanol. Finally
the solvent was removed affording the desired product in satis-
factory yield. The structures of the final products were con-
It could seem surprising that in the present case the break-
point lies at a pKLG value considerably higher than those for
carbonyl derivatives. However, it must be taken into account
that in the system under scrutiny the acyl moiety bears two
additional methyl groups and that the effect on rate of substitu-
ent is quite large, as we have recently shown.2 Allowance for this
can be made as follows: if the dotted line having slope Ϫ1.55
(this is again the βLG value for the hydrolysis of aryl 4-hydroxy-
3,5-dimethylbenzenesulfonates but it can be applied to aryl 4-
hydroxybenzenesulfonates) is drawn through the point corre-
sponding to log kapp for 2,4-dinitrophenyl 4Ј-hydroxybenzene-
sulfonate (4.139,2 solid circle in Fig. 2) and another dotted line
of slope Ϫ0.78 (see above) is drawn through the point referring
to log kcalc for 2,4-dinitrophenyl 4Ј-hydroxybenzenesulfonate
(0.613, open circle in Fig. 2; obtained through the procedure
described before for the dimethyl derivative) then the inter-
section between these lines, which lies at pKLG ca. 8.7, will
represent the changeover point from ElcB to SN2(S) mechanism
for the hydrolysis of aryl 4-hydrobenzenesulfonates.
However, such a break-point still occurs at a pKLG value
higher than those related to carbonyl derivatives, indicating
that, as far as the influence on mechanism of the leaving group
ability is concerned, aryl sulfonates seem to be more prone to
react via the dissociative pathway (in juxtaposition with the
associative one) than the corresponding carboxylates. This
inference, which agrees with the well known fact that the carb-
onyl carbon atom undergoes nucleophilic attack considerably
more readily than the sulfonyl sulfur,11 will be thoroughly dis-
cussed in a forthcoming paper.
1
firmed by H NMR spectroscopy. The esters recrystallized to
constant mp were as follows; mp is given together with ana-
lytical data.
Aryl
3,5-dimethyl-4-hydroxybenzenesulfonate.
Aryl = 4-
chloro-2-nitrophenyl. Mp 173–174 ЊC (from ethanol) (Found: C,
47.1; H, 3.4; N, 3.9. Calc. for C14H12NO6ClS: C, 47.0; H, 3.4;
N, 3.9%).
Aryl = 2-chloro-4-nitrophenyl. Mp 145–146 ЊC (from ethanol)
(Found: C, 471; H, 3.4; N, 3.9. Calc. for C14H12NO6ClS: C, 47.0;
H, 3.4; N, 3.9%).
Aryl = 4-nitrophenyl. Mp 148–149 ЊC (from benzene) (Found:
C, 52.3; H, 4.0; N, 4.5. Calc. for C14H13NO6S: C, 52.0; H, 4.1;
N, 4.3%).
Aryl = 3-nitrophenyl. Mp 145–146 ЊC (from benzene) (Found:
C, 52.0; H, 4.0; N, 4.4. Calc. for C14H13NO6S: C, 52.0; H, 4.1;
N, 4.3%).
Aryl = 2,5-dinitrophenyl. Mp 162–163 ЊC (from toluene)
(Found: C, 45.6; H, 3.2; N, 7.4. Calc. for C14H12N2O8S: C, 45.7;
H, 3.3; N, 7.6%).
Aryl = 4-methyl-2-nitrophenyl. Mp 220–221 ЊC (from tolu-
ene) (Found: C, 54.0; H, 4.5; N, 3.9. Calc. for C15H15NO6S: C,
53.4; H, 4.5; N, 4.1%).
Aryl = 5-methyl-2-nitrophenyl. Mp 134–135 ЊC (from
toluene) (Found: C, 53.4; H, 4.4; N, 4.3. Calc. for C15H15NO6S:
C, 53.4; H, 4.5; N, 4.1%).
The dissociative nature of the process under investigation is
also supported by the evaluation of the effective charge14 on the
leaving aryl oxygen in the transition state of the rate-limiting
step. The effective charge changes involved in this reaction are
depicted in Scheme 2. Since the overall change for an aryl
‡
–
OH
O–
O
O
+
ArO–
Aryl = 4,6-dichloro-2-nitrophenyl. Mp 174–175 ЊC (from
toluene) (Found: C, 43.1; H, 2.8; N, 3.3. Calc. for C14H11NO6-
Cl2S: C, 42.9; H, 2.8; N, 3.6%). The synthesis of 2,4-
dinitrophenyl ester has been previously reported.1b
(–1.0)
SO2 OAr
(+0.8)
SO2 OAr
(+0.73)
SO2
OAr
SO2
(–0.75)
βLG = –1.55
βNu = 0.25
‡
Methods
β
EQ = –1.8
Kinetic and other methods including the determination of pKa
of the substrates were described in a previous paper.10 The rate
constants for the hydrolysis of 3- and 4-nitrophenyl esters were
obtained by initial rates: they were measured for each run up to
ca. 10% of the total reaction and were converted to pseudo-
first-order rate constants using infinity values calculated from
the known extinction coefficients of the products.
Ionization constant of substituted phenol. The spectrophoto-
metric determinations of pKa of 5-methyl-2-nitrophenol
(7.32 0.01) and 4,6-dichloro-2-nitrophenol (4.40 0.02) were
carried out in water 25 ЊC respectively in phosphate buffers at
416 nm and in acetate buffers at 434 nm.
Scheme 2
sulfonate is Ϫ1.8,14a we can calculate, from the βLG value deter-
mined in this work, the effective charge residing on the oxygen
in the transition state (Ϫ1.55 ϩ 0.8 = Ϫ0.75) which is indicative
of extensive bond fission. In terms of Leffler’s index,14a the
value of α (0.86) supports this conclusion as well.
Experimental
General
Starting reagents and solvents were purified and/or distilled
before use. Buffer materials were of analytical reagent grade.
Water was double distilled and preboiled to free it from dis-
References
1 (a) S. Thea, G. Guanti, A. R. Hopkins and A. Williams, J. Am.
Chem. Soc., 1982, 104, 1128; (b) S. Thea, G. Cevasco, G. Guanti,
1
solved carbon dioxide. The H NMR spectra were recorded
J. Chem. Soc., Perkin Trans. 2, 1997
2217
Cevasco, Giorgio
