Kinetic investigation of the reactions of S-4-nitrophenyl 4-substituted thiobenzoates with secondary alicyclic amines in aqueous ethanol

Article abstract of DOI:10.1021/jo0348120

The reactions of S-4-nitrophenyl 4-X-substituted thiobenzoates (X = H, Cl, and NO₂: 1, 2, and 3, respectively) with a series of secondary alicyclic amines (SAA) were subjected to a kinetic investigation in 44 wt % ethanol-water, at 25.0 °C and an ionic strength of 0.2 M (KCl). The reactions were followed spectrophotometrically by monitoring the release of 4-nitrobenzenethiolate anion at 420-425 nm. Under excess amine, pseudo-first-order first-order rate constants (k_obsd) are obtained for all reactions. The plots of k_obsd vs [SAA] at constant pH are linear with the slope (k_N) independent of pH. The statistically corrected Bronsted-type plots (log k_N/q vs pK_a + log p/q) for the reactions of 1 and 2 are nonlinear with slopes at high pK _a, β₁ = 0.27 and 0.10, respectively, and slopes at low pK_a, β₂ = 0.86 and 0.84, respectively. The Bronsted curvature is centered at pK_a (pK_a ⁰) 10.0 and 10.4, respectively. The reactions of SAA with 3 exhibit a linear Bronsted-type plot of slope 0.81. These results are consistent with a stepwise mechanism, through a zwitterionic tetrahedral intermediate (Ti^±). For the reactions of 1 and 2, there is a change in rate-determining step with amine basicity, from T^± breakdown to products at low pK_a, to T^± formation at high pK_a. For the reactions of 3, breakdown to products of T ^± is rate limiting for all the SAA series (pK_a ⁰ > 11). The increasing pK_a⁰ value as the substituent in the acyl group becomes more electron withdrawing is attributed to an increasing nucleofugality of SAA from T^±. The greater pK_a⁰ value for the reactions of SAA with 1, relative to that found in the pyridinolysis of 2,4-dinitrophenyl benzoate (pK _a⁰ = 9.5), is explained by the greater nucleofugality from T^± of the former amines, compared to isobasic pyridines, and the greater leaving ability from T^± of 2,4-dinitrophenoxide relative to 4-nitrobenzenethiolate.

Full text of DOI:10.1021/jo0348120

Kin etic In vestiga tion of th e Rea ction s of S-4-Nitr op h en yl
4-Su bstitu ted Th ioben zoa tes w ith Secon d a r y Alicyclic Am in es in
Aqu eou s Eth a n ol
Enrique A. Castro,* J orge Bessolo, Raul Aguayo, and J ose´ G. Santos
Facultad de Qu´ımica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
ecastro@puc.cl
Received J une 11, 2003
The reactions of S-4-nitrophenyl 4-X-substituted thiobenzoates (X ) H, Cl, and NO2: 1, 2, and 3,
respectively) with a series of secondary alicyclic amines (SAA) were subjected to a kinetic
investigation in 44 wt % ethanol-water, at 25.0 °C and an ionic strength of 0.2 M (KCl). The
reactions were followed spectrophotometrically by monitoring the release of 4-nitrobenzenethiolate
anion at 420-425 nm. Under excess amine, pseudo-first-order rate constants (kobsd) are obtained
for all reactions. The plots of kobsd vs [SAA] at constant pH are linear with the slope (kN) independent
of pH. The statistically corrected Brønsted-type plots (log kN/q vs pKa + log p/q) for the reactions
of 1 and 2 are nonlinear with slopes at high pKa, â1 ) 0.27 and 0.10, respectively, and slopes at low
0
pKa, â2 ) 0.86 and 0.84, respectively. The Brønsted curvature is centered at pKa (pKa ) 10.0 and
10.4, respectively. The reactions of SAA with 3 exhibit a linear Brønsted-type plot of slope 0.81.
These results are consistent with a stepwise mechanism, through a zwitterionic tetrahedral
intermediate (T(). For the reactions of 1 and 2, there is a change in rate-determining step with
amine basicity, from T( breakdown to products at low pKa, to T( formation at high pKa. For the
0
reactions of 3, breakdown to products of T( is rate limiting for all the SAA series (pKa > 11). The
0
increasing pKa value as the substituent in the acyl group becomes more electron withdrawing is
attributed to an increasing nucleofugality of SAA from T(. The greater pKa0 value for the reactions
0
of SAA with 1, relative to that found in the pyridinolysis of 2,4-dinitrophenyl benzoate (pKa
)
9.5), is explained by the greater nucleofugality from T( of the former amines, compared to isobasic
pyridines, and the greater leaving ability from T( of 2,4-dinitrophenoxide relative to 4-nitroben-
zenethiolate.
In tr od u ction
The pyridinolysis of 2,4-dinitrophenyl 4-substituted
benzoates in aqueous ethanol proceeds through an in-
termediate T(; its breakdown to products is rate limiting
for the reactions of all pyridines with substrates possess-
ing electron-withdrawing substituents at the acyl group.5a,b
On the other hand, formation of T( is the rate-determin-
ing step for the reactions of the unsubstituted benzoate
with the two more basic pyridines.5c
Although there is abundant literature on the kinetics
and mechanisms of the aminolysis of thiocarbonates1,2
and thioalkanoates,1,3 there is much less information on
the kinetics of the same reactions of thiobenzoates.1,4 The
latter reports include the aminolysis (anilines) of S-aryl
thiobenzoates (aryl thiolbenzoates, X-C6H4-CO-SAr) in
methanol, where a concerted mechanism was found,4a in
contrast to the reactions of the same substrates with
benzylamines4b and pyridines4c in acetonitrile, where
stepwise processes were observed, with the formation of
a zwitterionic tetrahedral intermediate (T(). On the other
hand, for the reactions of primary and secondary amines
with 4-nitrophenyl thionobenzoate (C6H5-CS-OC6H4NO2)
in aqueous DMSO, stepwise mechanisms were found.4d
To shed some light on the kinetics and mechanisms of
the aminolysis of S-aryl thiobenzoates (aryl thiolben-
zoates), in this work we investigate the kinetics of the
(3) Oh, H. K.; Lee, J . Y.; Lee, I. Bull. Korean Chem. Soc. 1998, 19,
1198. Oh, H. K.; Kim, S. K.; Lee, I. Bull. Korean Chem. Soc. 1999, 20,
1017. Oh, H. K.; Yang, J . H.; Lee, H. W.; Lee, I. Bull. Korean Chem.
Soc. 1999, 20, 1418. Oh, H. K.; Yang, J . H.; Cho, I. H.; Lee, H. W.;
Lee, I. Int. J . Chem. Kinet. 2000, 32, 485. Oh, H. K.; J eong, J . Bull.
Korean Chem. Soc. 2001, 22, 1123. Oh, H. K.; Kim, S. K.; Lee, H. W.;
Lee, I. New J . Chem. 2001, 25, 313. Lee, I.; Lee, H. W.; Lee, B. C.;
Choi, J . H. Bull. Korean Chem. Soc. 2002, 23, 201. Um, I.-H.; Lee,
E.-J .; Lee, J .-P. Bull. Korean Chem. Soc. 2002, 23, 381. Oh, H. K.; Lee,
J . Y.; Lee, H. W.; Lee, I. New J . Chem. 2002, 26, 473. Rajarathnam,
D.; Babu, J .; Nadar, P. A. Int. J . Chem. Kinet. 2002, 34, 18. Oh, H. K.;
Ku, M. H.; Lee, H. W.; Lee, I. J . Org. Chem. 2002, 67, 3874. Oh, H. K.;
Ku, M. H.; Lee, H. W.; Lee, I. J . Org. Chem. 2002, 67, 8995.
(4) (a) Lee, I.; Shim, C. S.; Lee, H. W. J . Chem. Res., Synop. 1992,
90. (b) Lee, I.; Koh, H. J . New J . Chem. 1996, 20, 131. (c) Koh, H. J .;
Han, K. L.; Lee, I. J . Org. Chem. 1999, 64, 4783. (d) Um, I.-H.; Lee,
S.-E.; Kwon, H.-J . J . Org. Chem. 2002, 67, 8999.
(5) (a) Castro, E. A.; Steinfort, G. B. J . Chem. Soc., Perkin Trans. 2
1983, 453. (b) Castro, E. A.; Valdivia, J . L. J . Org. Chem. 1986, 51,
1668. (c) Castro, E. A.; Santander, C. L. J . Org. Chem. 1985, 50, 3595.
* Corresponding author.
(1) Castro, E. A. Chem. Rev. 1999, 99, 3505.
(2) (a) Oh, H. K.; Lee, J . Y.; Yun, J . H.; Park, Y. S.; Lee, I. Int. J .
Chem. Kinet. 1998, 30, 419. (b) Humeres, E.; Soldi, V.; Klug, M.; Nunes,
M.; Oliveira, C. M. S.; Barrie, P. J . Can. J . Chem. 1999, 77, 1050. (c)
Oh, H. K.; Lee, Y. H.; Lee, I. Int. J . Chem. Kinet. 2000, 32, 131. (d)
Castro, E. A.; Leandro, L.; Millan, P.; Santos, J . G. J . Org. Chem. 1999,
64, 1953. (e) Castro, E. A.; Saavedra, C.; Santos, J . G.; Uman˜a, M. I.
J . Org. Chem. 1999, 64, 5401. (f) Castro, E. A.; Mun˜oz, P.; Santos, J .
G. J . Org. Chem. 1999, 64, 8298. (g) Castro, E. A.; Garcia, P.; Leandro,
L.; Quesieh, N.; Rebolledo, A.; Santos, J . G. J . Org. Chem. 2000, 65,
9047. (h) Castro, E. A.; Leandro, L.; Quesieh, N.; Santos, J . G. J . Org.
Chem. 2001, 66, 6130. (i) Castro, E. A.; Galvez, A.; Leandro, L.; Santos,
J . G. J . Org. Chem. 2002, 67, 4309. (j) Faissat, L.; Chavis, C.; Montero,
J .-L.; Lucas, M. J . Chem. Soc., Perkin Trans. 1 2002, 1253.
10.1021/jo0348120 CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/25/2003
J . Org. Chem. 2003, 68, 8157-8161
8157

Castro et al.
TABLE 1. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Rea ction s of SAA w ith S-4-Nitr op h en yl Th ioben zoa te
(1)a
TABLE 2. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Rea ction s of SAA w ith S-4-Nitr op h en yl
4-Ch lor oth ioben zoa te (2)a
103[NH]tot
Mc
/
103kobsd
/
no. of
runs
103[NH]tot
Mc
/
103kobsd
/
no. of
runs
s-1
SAA
piperidine
pH
FN
s-1
b
b
SAA
piperidine
pH
FN
10.52 0.33
10.82 0.50
11.12 0.67
9.41 0.33
9.71 0.50
10.01 0.67
1.0-10
1.0-10
1.0-9.0
1.0-10
1.0-10
1.0-10
1.0-10
1.0-10
1.0-10
1.0-10
1.0-10
4.0-10
28-140
10-100
10-100
10-80
1.21-12.7
2.12-18.2
3.68-24.0
0.67-4.3
10
10
9
10
10
10
10
10
10
8
9
7
9
10
10
7
10.52 0.33
10.82 0.50
11.12 0.67
9.41 0.33
9.71 0.50
10.01 0.67
1.0-9.0
2.0-10
1.0-9.0
1.0-10
1.0-10
1.0-9.0
4.0-40
4.0-40
4.0-40
20-200
20-200
20-200
40-400
18-180
35-70
3.92-20.5
5.53-25.2
7.30-38.0
1.44-12.3
2.40-16.7
2.62-23.7
1.30-13.6
1.55-14.6
3.04-22.0
3.31-33.2
5.91-42.3
5.40-55.4
1.11-9.55
0.80-5.74
8
9
8
10
9
9
10
10
10
10
10
10
10
10
6
piperazine
piperazine
0.77-5.95
1.01-9.99
0.14-1.41
0.25-2.52
0.30-3.27
0.12-0.76
0.16-1.46
0.58-1.77
0.27-1.23
0.15-1.51
0.23-1.93
1-(2-hydroxyethyl)- 8.79 0.33
1-(2-hydroxyethyl)- 8.79 0.33
piperazine
9.09 0.50
9.39 0.67
8.18 0.33
8.48 0.50
8.78 0.67
7.33 0.33
7.63 0.50
7.93 0.67
5.07 0.33
5.37 0.50
piperazine
9.09 0.50
9.39 0.67
8.18 0.33
8.48 0.50
8.78 0.67
7.63 0.50
7.93 0.67
5.07 0.33
5.37 0.50
5.67 0.67
morpholine
morpholine
1-formylpiperazine
1-formylpiperazine
piperazinium ion
0.0080-0.020
0.017-0.045
0.013-0.11
piperazinium ion
0.0050-0.022
0.0044-0.040
30-100
15-150
8
10
10-90
7
a
a
In 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M
(KCl). b Fraction of free amine. c Concentration of total amine (free
amine plus its conjugate acid).
In 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M
(KCl). b Fraction of free amine. c Concentration of total amine (free
amine plus its conjugate acid).
TABLE 3. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Rea ction s of SAA w ith S-4-Nitr op h en yl
4-Nitr oth ioben zoa te (3)a
reactions of S-4-nitrophenyl 4-X-substituted thioben-
zoates (1, 2, and 3) with a series of secondary alicyclic
103[NH]tot
Mc
/
103kobsd
/
no. of
runs
SAA
piperidine
pH
FN
s-1
b
10.52 0.33 1.0-10
10.82 0.50 1.0-10
11.12 0.67 1.0-9.0
9.41 0.33 1.0-10
9.71 0.50 1.0-9.0
10.01 0.67 1.0-8.0
27.7-215
33.7-308
58.6-376
9
7
7
8
9
8
8
8
8
8
8
8
7
8
7
7
7
7
piperazine
5.17-46.6
6.26-56.7
8.20-64.9
1.77-8.17
2.11-11.7
0.77-17.5
0.69-4.44
1.03-6.48
1.12-9.54
0.030-0.48
0.025-0.86
0.26-1.11
0.0012-0.11
0.020-0.16
0.0063-0.23
1-(2-hydroxyethyl)- 8.79 0.33 3.0-10
amines (SAA) in aqueous ethanol. Specific goals are the
assessment of the influence of the nature of the amine
nucleophile, the solvent, and the substituents at both the
acyl and leaving groups of the substrate on the kinetics
and mechanisms of these reactions. These goals will be
achieved by comparisons of the title reactions between
them, and with the aminolyses of aryl thiolbenzoates in
other solvents4a-c and aryl benzoates in aqueous ethanol.5
piperazine
9.09 0.50 2.0-10
9.39 0.67 1.0-10
8.18 0.33 1.0-10
8.48 0.50 1.0-10
8.78 0.67 1.0-9.0
7.33 0.33 3.0-10
7.63 0.50 1.0-10
7.93 0.67 2.0-9.0
5.07 0.33 20-100
5.37 0.50 30-100
5.67 0.67 20-90
morpholine
1-formylpiperazine
piperazinium ion
Exp er im en ta l Section
a
In 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M
(KCl). b Fraction of free amine. c Concentration of total amine (free
amine plus its conjugate acid).
Ma ter ia ls. The series of SAA employed were purified either
by distillation or recrystallization.6 The three thiolbenzoates
1, 2, and 3 were synthesized from the substituted benzoyl
chloride and 4-nitrobenzenthiol, as described.7 Their melting
points were in accordance with literature values,8 and their
1H and 13C NMR spectra and elemental analyses agreed with
their structures.
The 4-X-substituted benzamides (X ) H, Cl, NO2) of pip-
eridine and morpholine (one of the products of the reactions
of these amines with 1, 2, and 3, respectively) were prepared
from the substituted benzoyl chloride and the corresponding
amine, as reported.9
Kin etic Mea su r em en ts. These measurements were car-
ried out spectrophotometrically (420-425 nm) by following the
release of 4-nitrobenzenethiolate anion (at pH values higher
than 7), or a mixture of this anion and its conjugate acid (at
pH ca. 5). The reactions were studied in 44 wt % ethanol-
water solutions, at 25.0 ( 0.1 °C, and an ionic strength of 0.2
M (maintained with KCl). This particular solvent was chosen
to compare the kinetics and mechanism of these reactions with
those reported for the pyridinolysis of 2,4-dinitrophenyl 4-sub-
stituted benzoates in 44 wt % ethanol-water.5 Three pH
values were usually employed for the reactions of each amine;
these were maintained by partial protonation of the amines.
At least a 10-fold excess of total amine (free amine plus its
conjugate acid) over the substrate was used in all reactions.
The initial substrate concentration was 5 × 10-5 M in all runs.
Pseudo-first-order rate coefficients (kobsd) were found in all
cases. These were obtained by means of the kinetic software
of the spectrophotometer, after at least 4 half-lives, except for
the slowest reactions (piperazinium cation with 1 and 2),
where the initial rate method was used.10
The experimental conditions of the reactions and the kobsd
values are shown in Tables 1-3.
P r od u ct Stu d ies. 4-Nitrobenzenethiolate anion was identi-
fied as one of the products in the aminolysis of 1, 2, and 3.
This was achieved by comparison of the UV-vis spectra after
completion of these reactions with those of an authentic sample
of 4-nitrobenzenethiol under the same reaction conditions.
(6) Castro, E. A.; Ureta, C. J . Org. Chem. 1989, 54, 2153.
(7) Bunton, C. A.; Foroudian, H. J .; Kumar, A. J . Chem. Soc., Perkin
Trans. 2 1995, 33.
(8) Cilento, G. J . Am. Chem. Soc. 1953, 75, 3748. Kanaoka, Y.;
Tanizawa, K.; Sato, E.; Yonemitsu, O.; Ban, Y. Chem. Pharm. Bull.
1967, 15, 593.
(9) Cabre, J . Synthesis 1984, 413. Cabre, J . Tetrahedron Lett. 1976,
219.
(10) Ba-Saif, S.; Luthra, A. K.; Williams, A. J . Am. Chem. Soc. 1987,
109, 6362.
8158 J . Org. Chem., Vol. 68, No. 21, 2003

Reactions of Thiobenzoates with Amines
TABLE 4. Va lu es of p Ka of th e Con ju ga te Acid s of SAA a n d kN for th e Rea ction s of SAA w ith S-4-Nitr op h en yl
Th ioben zoa te (1), S-4-Nitr op h en yl 4-Ch lor oth ioben zoa te (2), a n d S-4-Nitr op h en yl 4-Nitr oth ioben zoa te (3)a
kN/s-1 M-1
SAA
pKa
1
2
3
piperidine
piperazine
1-(2-hydroxyethyl)piperazine
morpholine
1-formylpiperazine
piperazinium ion
10.82
9.71
9.09
8.48
7.63
5.37
3.9 ( 0.2
5.2 ( 0.2
61 ( 2
1.5 ( 0.1
3.7 ( 0.2
12.5 ( 0.5
0.47 ( 0.02
0.79 ( 0.03
0.42 ( 0.01
0.050 ( 0.002
0.0012 ( 0.0001
2.8 ( 0.1
1.40 ( 0.1
0.19 ( 0.01
0.0043 ( 0.0002
0.25 ( 0.01
0.028 ( 0.001
(8.7 ( 0.6) × 10-4
a
Both the pKa and kN values were determined in 44 wt % ethanol-water, at 25.0 °C, ionic strength 0.2 M (KCl).
In the reactions of piperidine and morpholine with 1, 2, and
3, the corresponding 4-X-substituted benzamides (with X )
H, Cl, and NO2, respectively) were found as the other product
(besides 4-nitrobenzenethiolate anion) of these reactions. All
these products were identified by comparison of the UV-vis
spectra at the end of the reactions with those of an equimolar
mixture of the corresponding amide and 4-nitrobenzenethiol,
under the same experimental conditions of the reactions.
Resu lts a n d Discu ssion
The rate law obtained for all the reactions studied is
given by eqs 1 and 2, where NPS-, S, and NH represent
4-nitrobenzenethiolate anion, the substrate, and the free
amine, respectively, and k0 and kN are the rate coef-
ficients for solvolysis and aminolysis of the substrates,
respectively.
d[NPS-]
dt
kobsd ) k0 + kN[NH]
) kobsd[S]
(1)
(2)
F IGURE 1. Brønsted-type plots (statistically corrected) for
the reactions of SAA with 1 (b) and 3 (O) in 44 wt % ethanol-
water, at 25.0 °C, ionic strength 0.2 M (KCl).
The value of k0 was much lower than those of kN[NH]
in eq 2, except for the slow reactions of piperazinium
cation with the three substrates, where the aminolysis
term in eq 2 was also small. The values of kN for all
reactions were obtained as the slope of linear plots of kobsd
vs [NH]. The kN values were found to be pH independent.
These kN values are shown in Table 4, together with the
pKa values of the conjugate acids of the series of amines
(SAA) employed.
It can be seen in Table 4 that the values of kN for the
reactions of the substrates with a given amine increase
with the increasing electron-withdrawing ability of the
substituent on the acyl group of the thiolbenzoate. This
could be interpreted by the greater electron attraction
exerted by the 4-nitro substituent in 3, which would leave
its carbonyl carbon more positively charged, compared
with the other less electron-attracting substituents, and
therefore more prone to nucleophilic attack by the amine.
Nevertheless, Neuvonen and co-workers have recently
shown that electron-withdrawing substituents on both
the acyl and leaving groups of esters increase the electron
density at the carbonyl carbon.11 The greater reactivity
toward a nucleophile of esters with powerful electron-
withdrawing substituents was explained by ground-state
destabilization of the ester due to the decreased reso-
nance stabilization.11 This destabilization of the ground
state should not be as great as that of the transition state,
implying a smaller free energy of activation for the
reaction of an ester with a stronger electron-withdrawing
substituent.
The values of kN and pKa of Table 4 were corrected
statistically before plotting the Brønsted-type equation.
The former values are corrected by dividing kN by q,
where q is the number of equivalent basic sites of the
free SAA (q ) 2 for piperazine and q ) 1 for the other
SAA).6,12 The Ka values are corrected by multiplying Ka
by q/p, where p is the number of equivalent protons of
the conjugate acid of SAA (p ) 4 for the conjugate acid
of piperazinium cation and p ) 2 for the conjugate acids
of the other amines).6,12
Figure 1 shows the statistically corrected Brønsted-
type plots for the aminolysis of thiolbenzoates 1 and 3,
and Figure 2 shows the corresponding plot for the
reactions of the same amines with thiolbenzoate 2. The
plot for 3 is linear with slope â ) 0.81 ( 0.03, whereas
the other plots are nonlinear.
The curved Brønsted-type plots for the aminolyis of 1
and 2 are consistent with a stepwise mechanism (shown
in Scheme 1), through a zwitterionic tetrahedral inter-
mediate (T() and a change in the rate-determining step,
from T( decomposition to products (k2 step in Scheme 1)
to formation of T( (k1 step), as the amine becomes more
(11) Neuvonen, H.; Neuvonen, K.; Koch, A.; Kleinpeter, E.; Pasanen,
P. J . Org. Chem. 2002, 67, 6995.
(12) Bell, R. P. The proton in Chemistry; Methuen: London, UK,
1959; p 159.
J . Org. Chem, Vol. 68, No. 21, 2003 8159

Castro et al.
The values of â1 and â2 obtained in the reactions
studied in the present work are in agreement with those
obtained for the stepwise aminolysis of esters,5,14,15
carbonates,13,16,17 and their thio analogues1,4c,d,6,18 (â2 )
0.1-0.3 and â2 ) 0.8-1.0).
In light of the proposed mechanism for the present
reactions (Scheme 1), deprotonation of the intermediate
T( by an amine to yield an anionic tetrahedral interme-
diate (k3 step) is not fast enough to compete with the k2
step. Competition between these two steps (k3 and k2)
has been observed for relatively bad nucleofuges (com-
pared with 4-nitrobenzenethiolate) and/or substrates
with a thiocarbonyl group, instead of carbonyl.1,2e,g-i This
has been explained by the lower ability of S- in the
zwitterionic tetrahedral intermediate formed in the ami-
nolysis of thionocarbonates and dithiocarbonates to form
a CdS double bond and expel the nucleofuge, compared
with the ability of O- in the corresponding intermediate
to form a CdO bond. This means a lower k2 value for
breakdown of the intermediate with S- relative to that
for an intermediate with O-.1,2e,g-i
F IGURE 2. Brønsted-type plot (statistically corrected) for the
reactions of SAA with 2 in 44 wt % ethanol-water, at 25.0
°C, ionic strength 0.2 M (KCl).
0
According to our results, the pKa value increases as
the substituent on the acyl group of the substrate
0
becomes more electron withdrawing (pKa ) 10.0, 10.4,
SCHEME 1
and >10.8, for the reactions of 1, 2, and 3, respectively).
This is in accordance with the results of Gresser and
J encks in the reactions of quinuclidines with diaryl car-
bonates.19 They found that electron attraction from the
group that does not leave favors amine expulsion (com-
pared to ArO- expulsion) from the zwitterionic tetrahe-
0
dral intermediate. This means that the value of pKa
should increase with the increase of electron withdrawal
from the nonleaving group of the substrate, according to
eq 4.20 The values of â2 and â1 do not change significantly
with the amine or the substrate nature.1,4c,d,5,6,13-19
basic.1,4c,d,5,6,13 The curved lines of the Brønsted plots for
the reactions of 1 and 2 were calculated through a
semiempirical equation (eq 3) based on the above
0
log(k-1/k2) ) (â2 - â1)(pKa - pKa)
(4)
0
The shift of the pKa value with the change of the acyl
substituent is another proof that the title reactions are
stepwise. In the concerted aminolysis of benzoyl fluorides,
where a slight Brønsted curve has been observed, the pKa
value at the center of the Brønsted curve does not change
with the acyl substituents.21 This was argued to be
diagnostic of concerted mechanisms.21
hypothesis.4d,5c,6,13 In this equation, kN and pKa are the
corresponding parameters for the center of the Brønsted
curvature, i.e., for an (hypothetical) amine that leaves
T( as fast as the leaving group of the substrate (k-1 ) k2
in Scheme 1). The parameters â1 and â2 are the slopes of
the linear portions of the Brønsted plot, at high and low
pKa values, respectively. The parameters obtained in the
fitting of eq 3 to the experimental points are the follow-
ing: log kN0 ) 0.07, pKa0 ) 10.0, â1 ) 0.27, and â2 ) 0.86
0
0
0
The shift of pKa with acyl substituents observed in
the present work is also in agreement with the results
found for the stepwise reactions of 2,4-dinitrophenyl 4-X-
substituted benzoates (X ) H, Cl, and NO2) with a series
0
for the reactions of thiolbenzoate 1 and log kN ) 0.56,
0
pKa ) 10.4, â1 ) 0.10, and â2 ) 0.84 for the reactions of
0
thiolbenzoate 2. The errors of the values of pKa and the
(14) J ohnson, S. L. Adv. Phys. Org. Chem. 1967, 5, 237.
(15) Satterthwait, A. C.; J encks, W. P. J . Am. Chem. Soc. 1974, 96,
7018.
(16) (a) Bond, P. M.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2
1976, 679. (b) Castro, E. A.; Gil, F. J . J . Am. Chem. Soc. 1977, 99,
7611. (c) Castro, E. A.; Freudenberg, M. J . Org. Chem. 1980, 45, 906.
(d) Castro, E. A.; Iban˜ez, F.; Lagos, S.; Schick, M.; Santos, J . G. J .
Org. Chem. 1992, 57, 2691.
slopes are 0.2 and 0.03, respectively.
0
log(kN/kN0) ) â2(pKa - pKa ) - log[(1 + a)/2] (3)
0
log a ) (â2 - â1)(pKa - pKa )
(17) Castro, E. A.; Aliaga, M.; Campodo´nico, P.; Santos, J . G. J . Org.
Chem. 2002, 67, 8911. Castro, E. A.; Andu´jar, M.; Campodo´nico, P.;
Santos, J . G. Int. J . Chem. Kinet. 2002, 34, 309. Castro, E. A.; Andu´jar,
M.; Toro, A.; Santos, J . G. J . Org. Chem. 2003, 68, 3608.
(18) Castro, E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991,
63.
(19) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6970.
(20) Castro, E. A.; Araneda, C. A.; Santos, J . G. J . Org. Chem. 1997,
62, 126.
The linear Brønsted-type plot of slope â2 ) 0.81 found
for the aminolysis of thiolbenzoate 3 (Figure 1) is in
accordance with the mechanism depicted in Scheme 1,
with decomposition of the intermediate T( to products
(step k2) being rate limiting.
(13) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963.
8160 J . Org. Chem., Vol. 68, No. 21, 2003
(21) Song, B. D.; J encks, W. P. J . Am. Chem. Soc. 1989, 111, 8479.

Reactions of Thiobenzoates with Amines
of pyridines in 44 wt % ethanol-water.5 The reactions
pyridinolysis of aryl acetates in water24,16c with the same
aminolysis of aryl benzoates in aqueous ethanol:5 the
values of kN are much larger for the former reactions.
of the unsubstituted benzoate show a curved Brønsted-
0
type plot centered at pKa ) 9.5,5c whereas those exhib-
ited in the pyridinolysis of the 4-chloro and 4-nitro
The reactions of anilines with S-4-nitrophenyl 4-X-
thiobenzoates (X ) H, Cl, NO2) in methanol were
subjected to a kinetic investigation and found to be
concerted, i.e., these reactions proceed in a single step,
with no formation of the zwitterionic tetrahedral inter-
mediate (T().4a These results are surprising taking into
account those obtained in the present work, for the
following reasons. We have shown that anilines are worse
nucleofuges than isobasic SAA from the intermediate T(,
i.e., the former amines stabilize kinetically T( relative
to isobasic SAA.2d On the other hand, methanol is a polar
solvent and its polarity should not be so different than
that of the solvent mixture used in the present investiga-
tion. Therefore, in the light of our results, it would be
expected that the reactions of anilines with S-4-nitro-
phenyl thiobenzoates in methanol were stepwise, and not
concerted, as found.
0
derivatives are linear, with slope â2 ca. 0.9, i.e., pKa
>
9.5.5a,b
0
The greater value of pKa found for the aminolysis
0
(SAA) of thiolbenzoate 1 in 44 wt % ethanol-water (pKa
) 10.0, this work) compared with that obtained for the
pyridinolysis of 2,4-dinitrophenyl benzoate in the same
solvent (pKa ) 9.5)5c can be explained through the
0
following analysis. 2,4-Dinitrophenoxide anion should be
a better nucleofuge from a zwitterionic tetrahedral
intermediate (T() than 4-nitrobenezenethiolate anion, as
judged by the lower pKa of the conjugate acid of the
former (pKa 4.1)22 than that of the latter (pKa 4.6).6
Moreover, it is known that ArO- is a better leaving group
than an isobasic Ar′S-.23 This means a larger k2 value
for the dinitro derivative. On the other hand, pyridines
are known to be worse nucleofuges from T( than isobasic
SAA,18 which indicates a smaller k-1 value for pyridines.
Therefore, for the reactions of 2,4-dinitrophenyl benzoate
with pyridines the k-1/k2 ratios are lower than those for
the reactions of thiolbenzoate 1 with isobasic SAA.
According to eq 4, this means a lower pKa0 for the former
reactions, as found.
The Hammett plot (not shown) for 4-X-acyl substitu-
ents (log kN vs σX) for the title reactions exhibits an
excellent linear correlation, with slope F ) 0.96 ( 0.04.
This is in accordance with the F values obtained for the
pyridinolysis of 2,4-dinitrophenyl 4-substituted benzoates
(F ) 1.06)5 and the stepwise benzylaminolysis of S-4-
bromophenyl 4-substituted thiobenzoates (F ) 0.94-
1.2).4b
The reactions of benzylamines with S-aryl 4-X-thioben-
zoates (X ) H, Cl, NO2) in acetonitrile are stepwise, with
rate-determining breakdown of T( to products.4b This is
consistent with the results of the present work on the
following grounds: it has been shown that aliphatic
primary amines are worse leaving groups from T( than
isobasic SAA,4d which means that the former amines
stabilize T( relative to SAA. On the other hand, aceto-
nitrile should destabilize the intermediate T( compared
with aqueous ethanol, in view of the lower polarity of the
former solvent. The fact that both reactions are stepwise
suggests that the amine effect is compensated by the
solvent effect.
The reactions of a series of SAA with S-4-nitrophenyl
thioacetate in water are governed by a stepwise mecha-
nism, as evidenced by the curved Brønsted-type plot
obtained, with slopes â2 ) 0.86 (low pKa region) and â1
) 0.10 (high pKa).6 There is a striking greater reactivity
toward SAA of the former thiolacetate in water compared
to that of thiolbenzoates 1-3 in aqueous ethanol (this
work), when either step is rate determining. This can be
attributed to (i) the greater steric hindrance to SAA
attack of the phenyl group in 1-3, relative to methyl in
S-4-nitrophenyl thioacetate, and (ii) the greater stabiliza-
tion by water, relative to the less polar aqueous ethanol
solvent, of the zwitterionic tetrahedral intermediate and
the transition states for its formation and breakdown.19
The same results were found by comparison of the
The pyridinolysis of S-aryl 4-nitrothiobenzoate in ac-
etonitrile is stepwise, as shown by the curved (biphasic)
Brønsted-type plot obtained.4c This is also in accordance
with the stepwise reactions of SAA with thiolbenzoate
3, since the stabilization of T( provided by pyridines
(compared to isobasic SAA)6 should be compensated by
its destabilization caused by acetonitrile (relative to
aqueous ethanol).
Ack n ow led gm en t. We thank FONDECYT of Chile
(project 1020524) for financial assistance to this work.
R.A. thanks “Direccio´n de Investigacio´n y Postgrado de
Pontificia Universidad Cato´lica de Chile (DIPUC)” for
a Doctoral scholarship. We also thank Dr. Florencia
Gonzalez for the synthesis of thiolbenzoate 1.
J O0348120
(22) Albert, A.; Serjeant, E. P. The Determination of Ionization
Constants; Chapman and Hall: London, UK, 1971; p 87.
(23) J ensen, J . L.; J encks, W. P. J . Am. Chem. Soc. 1979, 101, 1476.
Douglas, K. T.; Alborz, M. J . Chem. Soc., Chem. Commun. 1981, 551.
(24) J encks, W. P.; Gilchrist, M. J . Am. Chem. Soc. 1968, 90, 2622.
J . Org. Chem, Vol. 68, No. 21, 2003 8161