Effect of substituent on regioselectivity and reaction mechanism in aminolysis of 2,4-dinitrophenyl X-substituted benzenesulfonates

Article abstract of DOI:10.1021/jo048227q

(Chemical Equation Presented) We report on a kinetic study for the nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzensulfonates (X = 4-MeO, 1a, and X = 4-NO₂, 1c) with a series of primary amines in 80 mol % H₂O/20 mol % DMSO at 25.0 °C. The reactions proceed through S-O and C-O bond fission pathways competitively. The fraction of the S-O bond fission increases as the attaching amine becomes more basic and the substituent X changes from 4-MeO to 4-NO₂, indicating that the regioselectivity is governed by the electronic nature of the substituent X as well as the basicity of amines. The S-O bond fission has been suggested to proceed through an addition intermediate with a change in the rate-determining step (RDS) at pK°_a = 8.9 ± 0.1. The electronic nature of the substituent X influences k_N^S-O and k₁ values, but not the k₂/k_-1 ratios and the pK°_a value significantly. Stabilization of the ground state (GS) through resonance interaction between the electron-donating substituent and the electrophilic center has been suggested to be responsible for the decreased reactivity of 1a compared to 1c. The second-order rate constants for the C-O bond fission exhibit no correlation with the electronic nature of the substituent X. The distance effect and the nature of the reaction mechanism have been suggested to be responsible for the absence of the correlation.

Full text of DOI:10.1021/jo048227q

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Effect of Substituent on Regioselectivity and Reaction Mechanism
in Aminolysis of 2,4-Dinitrophenyl X-Substituted
Benzenesulfonates
Ik-Hwan Um,* Jin-Young Hong, and Jin-Ah Seok
Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea
ihum@mm.ewha.ac.kr
Received October 8, 2004
We report on a kinetic study for the nucleophilic substitution reactions of 2,4-dinitrophenyl
X-substituted benzensulfonates (X ) 4-MeO, 1a, and X ) 4-NO2, 1c) with a series of primary amines
in 80 mol % H2O/20 mol % DMSO at 25.0 °C. The reactions proceed through S-O and C-O bond
fission pathways competitively. The fraction of the S-O bond fission increases as the attaching
amine becomes more basic and the substituent X changes from 4-MeO to 4-NO2, indicating that
the regioselectivity is governed by the electronic nature of the substituent X as well as the basicity
of amines. The S-O bond fission has been suggested to proceed through an addition intermediate
with a change in the rate-determining step (RDS) at pKa° ) 8.9 ( 0.1. The electronic nature of the
S-O
substituent X influences kN
and k1 values, but not the k2/k-1 ratios and the pKa° value
significantly. Stabilization of the ground state (GS) through resonance interaction between the
electron-donating substituent and the electrophilic center has been suggested to be responsible for
the decreased reactivity of 1a compared to 1c. The second-order rate constants for the C-O bond
fission exhibit no correlation with the electronic nature of the substituent X. The distance effect
and the nature of the reaction mechanism have been suggested to be responsible for the absence
of the correlation.
Introduction
state (TS) and the zwitterionic intermediate for amino-
lysis of various carboxylic esters, recent computational
studies favor a stepwise mechanism over a concerted
pathway.14-16 Curved Brønsted-type plots, which have
often been obtained for aminolysis of carboxylic esters
with a good leaving group, also support a stepwise
mechanism.1-4 Thus, it is now firmly established that
reactions of esters with amines proceed in a stepwise
manner with a change in the RDS at pKa°, which has
been defined as the pKa value at the center of the
curvature of a curved Brønsted-type plot.1-4,7-12
Nucleophilic substitution reactions of carbon-, phos-
phorus-, and sulfur-centered esters have been the subject
of extensive experimental1-12 and theoretical studies.13-16
Aminolysis of esters has been suggested to proceed either
in a stepwise manner with one or two intermediates or
concertedly without an intermediate.1-16 Although some
computational results failed to identify the transition
(1) (a) Jencks, W. P. Chem. Rev. 1985, 85, 511-527. (b) Page, M. I.;
Williams, A. Organic and Bio-organic Mechanisms; Longman: Harlow,
UK, 1997; Chapter 7.
(2) (a) Castro, E. A. Chem. Rev. 1999, 99, 3505-3524. (b) Castro,
E. A.; Cubillos, M.; Aliaga, M.; Evangelisti, S.; Santos, J. G. J. Org.
Chem. 2004, 69, 2411-2416. (c) Castro, E. A.; Andujar, M.; Toro, A.;
Santos, J. G. J. Org. Chem. 2003, 68, 3608-3613. (d) Castro, E. A.;
Aliaga, M.; Campodonico, P.; Santos, J. G. J. Org. Chem. 2002, 67,
8911-8916. (e) Castro, E. A.; Andujar, M.; Campodonico, P.; Santos,
J. G. Int. J. Chem. Kinet. 2002, 34, 309-315. (f) Castro, E. A.; Galvez,
A.; Leandro, L.; Santos, J. G. J. Org. Chem. 2002, 67, 4309-4315.
(3) (a) Oh, H. K.; Kim, I. K.; Lee, H. W.; Lee, I. J. Org. Chem. 2004,
69, 3806-3810. (b) Oh, H. K.; Park, J. E.; Sung, D. D.; Lee, I. J. Org.
Chem. 2004, 69, 3150-3153. (c) Oh, H. K.; Ku, M. H.; Lee, H. W.; Lee,
I. J. Org. Chem. 2002, 67, 3874-3877. (d) Lee, H. W.; Guha, A. K.;
Lee, I. Int. J. Chem. Kinet. 2002, 34, 632-637. (e) Koh, H. J.; Kang, S.
J.; Kim, C. J.; Lee, H. W.; Lee, I. Bull. Korean Chem. Soc. 2003, 24,
925-930. (f) Song, H. B.; Choi, M. H.; Koo, I. S.; Oh, H. K.; Lee, I.
Bull. Korean Chem. Soc. 2003, 24, 91-94.
10.1021/jo048227q CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/21/2005
1438
J. Org. Chem. 2005, 70, 1438-1444

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
2,4-Dinitrophenyl X-Substituted Benzenesulfonates
Jencks et al. have found that the pKa° value increases
as the nonleaving phenoxy moiety becomes less basic
(more electron-withdrawing) in the reactions of X-sub-
stituted phenyl 3,4-dinitrophenyl carbonates with qui-
nuclidines.17 A similar result has been reported by Castro
et al. for the pyridinolysis of 2,4-dinitrophenyl X-sub-
stituted benzoates (X ) H, 4-Cl, and 4-NO2): pKa° ) 9.5
when X ) H, but pKa° > 9.5 when X ) 4-Cl and 4-NO2.18
More recently, the pKa° value for the aminolysis of S-4-
nitrophenyl X-substituted thiobenzoates has been shown
to increase from 10.0 to 10.4 and >11 as the substituent
in the nonleaving group X changes from H to 4-Cl and
4-NO2, respectively, in the reaction with alicyclic second-
ary amines,19a and pKa° ) 9.7 when X ) H but pKa° >
9.7 when X ) 4-Cl and 4-NO2 in the reaction with
pyridines.19b
An electron-withdrawing group (EWG) in the non-
leaving group has been suggested to favor amine expul-
sion (k-1) from the zwitterionic intermediate relative to
the leaving group departure (k2).17-19 Accordingly, Jencks
and Castro et al. have proposed that the k2/k-1 ratio
decreases on changing the substituent in the nonleaving
group from an EDG to an EWG, and the decrease in the
k2/k-1 ratio is responsible for the increase in the pKa°
value.17-19 However, we have shown that the k2/k-1 ratio
and pKa° value are not influenced significantly by chang-
ing the substituent in the nonleaving group from a strong
electron-donating group (EDG) to a strong EWG in the
reactions of 2,4-dinitrophenyl X-substituted benzoates
with a series of primary and alicyclic secondary amines.4a,20
(4) (a) Um, I. H.; Kim, K. H.; Park, H. R.; Fujio, M.; Tsuno, Y. J.
Org. Chem. 2004, 69, 3937-3942. (b) Um, I. H.; Seok, J. A.; Kim, H.
T.; Bae, S. K. J. Org. Chem. 2003, 68, 7742-7746. (c) Um, I. H.; Lee,
S. E.; Kwon, H. J. J. Org. Chem. 2002, 67, 8999-9005. (d) Um, I. H.;
Min, J. S.; Ahn, J. A.; Hahn, H. J. J. Org. Chem. 2000, 65, 5659-
5663. (e) Um, I. H.; Lee, E. J.; Lee, J. P. Bull. Korean Chem. Soc. 2002,
23, 381-384.
(5) (a) Williams. A. Chem. Soc. Rev. 1994, 23, 93-100. (b) Williams,
A. Adv. Phys. Org. Chem. 1992, 27, 1-55. (c) Williams, A. Concerted
Organic and Bio-organic Mechanisms; CRC Press: Boca Raton, FL,
1999. (d) Colthurst, M. J.; Williams, A. J. Chem. Soc., Perkin Trans.
2, 1997, 1493-1498. (e) Renfrew, A. H. M.; Rettura, D.; Taylor, J. A.;
Whitmore, J. M. J.; Williams, A. J. Am. Chem. Soc. 1995, 117, 5484-
5491. (f) D’Rozario, P.; Smyth, R. L.; Williams, A. J. Am. Chem. Soc.
1984, 106, 5027-5028.
(6) (a) Kice, J. L. Adv. Phys. Org. Chem. 1980, 17, 65-181. (b)
Ciuffarin, E.; Senatore, L.; Isola, M. J. Chem. Soc., Perkin Trans. 2
1972. 468-471. (c) King, J. F.; Gill, M. S.; Klassen, D. F. Pure Appl.
Chem. 1996, 68, 825-830.
(7) (a) Um, I. H.; Jeon, S. E.; Baek, M. H.; Park, H. R. Chem.
Commun. 2003, 3016-3017. (b) Um, I. H.; Hong, J. Y.; Buncel, E.
Chem. Commun. 2001, 27-28. (c) Um, I. H.; Kim, M. J.; Lee, H. W.
Chem. Commun. 2000, 2165-2166. (d) Um, I. H.; Lee, H. W,; Park, J.
Y. Tetrahedron Lett. 1999, 40, 8901-8904.
(8) (a) Tsaug, J. S. W.; Neverov, A. A.; Broen, R. S. J. Am. Chem.
Soc. 2003, 125, 1559-1566. (b) Morales-Rojas, J.; Moss, R. A. Chem.
Rev. 2002, 102, 2497-2522. (c) Toullec, J.; Mohamed, M. Chem.
Commun. 1996, 221-222. (d) Srivatsan, S. G.; Verma, S. Chem.
Commun. 2000, 515-516.
(9) (a) Terrier, F.; Le Guevel, E.; Chatrousse, A. P.; Moutiers, G.;
Buncel, E. Chem. Commun. 2003, 600-601. (b) Buncel, E.; Cannes,
C.; Chatrousse, A. P.; Terrier, F. J. Am. Chem. Soc. 2002, 124, 8766-
8767. (c) Omakor, J. E.; Onyido, I.; vanLoon, G. W.; Buncel, E. J. Chem.
Soc., Perkin Trans. 2, 2001, 324-330. (d) Tarkka, R. M.; Buncel, E. J.
Am. Chem. Soc. 1995, 117, 1503-1507. (e) Hoz, S.; Liu, P.; Buncel, E.
Chem. Commum. 1996, 995-996. (f) Tarkka, R. M.; Park, W. K. C.;
Liu, P.; Buncel, E. J. Chem. Soc., Perkin Trans. 2 1994, 2439-2444.
(g) Nagelkerke, R.; Thatcher, G. R. J.; Buncel, E. Org. Biomol. Chem.
2003, 1, 163-167. (h) Buncel, E.; Nagelkerke, R.; Thatcher, G. R. J.
Can. J. Chem. 2003, 81, 53-63.
(10) (a) Baxter, N. J.; Rigoreau, L. J. M.; Laws, A. P.; Page. M. I. J.
Am. Chem. Soc. 2000, 122, 3375-3385. (b) Spillane, W. J.; McGrath,
P.; Brack, C.; O’Byrne, A. B. J. Org. Chem. 2001, 66, 6313-6316. (c)
Gordon, I. M.; Maskill, H.; Ruasse, M. F. Chem. Soc. Rev. 1989, 18,
123-151.
(11) (a) Um, I. H.; Hong, J. Y.; Kim, J. J.; Chae, O. M.; Bae, S. K. J.
Org. Chem. 2003, 68, 5180-5185. (b) Um, I. H.; Chun, S. M.; Chae, O.
M.; Fujio, M.; Tsuno, Y. J. Org. Chem. 2004, 69, 3166-3172.
(12) (a) Um, I. H.; Han, H. J.; Ahn, J. A.; Kang, S.; Buncel, E. J.
Org. Chem. 2002, 67, 8475-8480. (b) Um, I. H.; Lee, J. Y.; Kim, H. T.;
Bae, S. K. J. Org. Chem. 2004, 69, 2436-2441.
(13) (a) Guthrie, R. D. Pure Appl. Chem. 1989, 61, 23. (b) Guthrie,
J. P. J. Am. Chem. Soc. 1991, 113, 3941-3949.
(14) (a) Zipse, H.; Wang, L.; Houk, K. N. Liebigs Ann. 1996, 1511-
1522. (b) Oie, T.; Loew, G. H.; Burt, S. K.; Binkley, J. S.; Mcelroy, R.
D. J. Am. Chem. Soc. 1982, 104, 6169-6174.
(15) (a) Lee, I.; Sung, D. D. Curr. Org. Chem. 2004, 8, 557-567. (b)
Lee, I.; Lee, H. W.; Lee, B. C.; Choi, J. H. Bull. Korean Chem. Soc.
2002, 23, 201-204. (c) Lee, H. W.; Guha, A. K.; Kim, C. K.; Lee, I. J.
Org. Chem. 2002, 67, 2215-2222.
(16) (a) Ilieva, S.; Galabov, B.; Musaev, D. G.; Morokuma, K.;
Schaefer, H. F., III. J. Org. Chem. 2003, 68, 1496-1502. (b) Yang, W.;
Drueckhammer, D. G. Org. Lett. 2000, 2, 4133-4136.
(17) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99, 6963-
6970.
(18) (a) Castro, E. A.; Santander, C. L. J. Org. Chem. 1985, 50,
3595-3600. (b) Castro, E. A.; Valdivia, J. L. J. Org. Chem. 1986, 51,
1668-1672. (c) Castro, E. A.; Steinfort, G. B. J. Chem. Soc., Perkin
Trans. 2 1983, 453-457.
We have recently performed a kinetic study for the
reactions of 2,4-dinitrophenyl benzenesulfonate (1b) with
a series of primary and secondary amines, and found that
the nature of amines (e.g., primary vs secondary amines)
does not influence the pKa° value and k2/k-1 ratio
significantly.11a,b To obtain more information about the
reaction mechanism, we have extended our kinetic study
to the reactions of 2,4-dinitrophenyl X-substitued ben-
zenesulfonates (X ) 4-MeO, 1a, and X ) 4-NO2, 1c) with
10 different primary amines in 80 mol % H2O/20 mol %
DMSO. We report the electronic effect of the substituent
X on regioselectivity, rate, and mechanism, including the
k2/k-1 ratio and pKa° value by comparing the kinetic data
for the reactions of 1a and 1c in this study with those
reported previously for the corresponding reaction of 1b.
Results and Discussion
The reactions of 1a and 1c with primary amines
proceed through S-O and C-O bond fission pathways
competitively as shown in Scheme 1. The fractions of the
S-O bond fission are summarized in Table 1. The S-O
bond fission that leads to formation of 2,4-dinitro-
phenoxide ion and substituted benzenesulfonamides was
found to occur exclusively in the reactions of 1b and 1c
with strongly basic amines. On the other hand, the C-O
bond fission that yields substituted anilines and benzene-
sulfonates was found to occur considerably in the reac-
tions of 1a with weakly basic amines, indicating that the
regioselectivity is governed by the basicity of amines as
well as the electronic nature of the substituent X in the
sulfonyl moiety.
All the reactions studied in this work obeyed pseudo-
first-order kinetics under excess amine over 90% of the
(19) (a) Castro, E. A.; Bessolo, J.; Aguayo, R.; Santos, J. G. J. Org.
Chem. 2003, 68, 8157-8161. (b) Castro, E. A.; Vivanco, M.; Aguayo,
R.; Aguayo, R.; Santos, J. G. J. Org. Chem. 2004, 69, 5399-5404.
(20) Um, I. H.; Min, J. S.; Lee, H. W. Can. J. Chem. 1999, 77, 659-
666.
J. Org. Chem, Vol. 70, No. 4, 2005 1439

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Um et al.
SCHEME 1
TABLE 1. Summary of Second-Order Rate Constants for the S-O Bond Fission in the Reaction of 1a-c with Primary
Amines in 80 Mol % H2O/20 Mol % DMSO at 25.0 ( 0.1 °Ca
103 x kNS-O (M-1 s-1
)
b
no.
amine
pKa
1a
1bc
1c
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
ethylamine
10.67
10.89
10.32
10.06
9.67
312 (0.94)
297 (0.96)
241 (0.93)
158 (0.93)
90.5 (0.91)
83.9 (0.86)
16.2 (0.84)
7.33 (0.76)
5.27 (0.76)
0.189 (0.67)
1290 (1.00)
1050 (1.00)
832 (1.00)
555 (1.00)
312 (1.00)
257 (0.99)
43.7 (0.97)
19.1 (0.89)
12.7 (0.89)
0.468 (0.79)
10500 (1.00)
8610 (1.00)
5960 (1.00)
3830 (1.00)
1860 (1.00)
1830 (1.00)
255 (1.00)
100 (0.99)
79.0 (0.97)
1.86 (0.92)
propylamine
ethylenediamine
glycine
ethanolamine
benzylamine
9.46
glycylglycine
8.51
glycine ethyl ester
1,2-diaminopropane-H+
trifluoroethylamine
7.68
7.13
5.70
a Data in parentheses are the fractions of S-O bond fission. b pKa data in 80 mol % H2O/20 mol % DMSO were taken from ref 11a.
c Rate constant data for the reaction of 1b were taken from ref 11a.
total reaction. Pseudo-first-order rate constants
(kobsd) were obtained from the equation, ln(A∞ - At) )
-kobsdt + c. Correlation coefficients of the linear regres-
sions were usually higher than 0.9995. Generally, five
different amine concentrations were used to obtain
second-order rate constants from the slope of the linear
plot of kobsd vs amine concentration. The plots of kobsd vs
amine concentration are linear passing through the
origin, indicating that the contribution by H2O and/or
HO- ion from the solvolysis to kobsd is negligible. The
second-order rate constant obtained in this way corre-
sponds to the overall second-order rate constant (kNtot).11
The kNtot values obtained in this way are summarized in
Table S1 in Supporting Information. The second-order
rate constant for the S-O bond fission (kNS-O) and the
one for the C-O bond fission (kNC-O) were calculated from
the following relationships:
FIGURE 1. Brønsted-type plots for the S-O bond fission in
tot
kNS-O ) kN × the fraction of S-O bond fission (1)
the reactions of 1a (4), 1b (O), and 1c (b) with primary amines
in 80 mol % H2O/20 mol % DMSO at 25.0 ( 0.1 °C. The
S-O
kNC-O ) kNtot - kN
(2)
numbers refer to the amines in Table 1. The solid lines were
calculated by eq 3.
21
using p and q
for the reactions of 1a-c exhibit a
Reaction Mechanism for S-O Bond Fission. As
shown in Table 1, the reactivity of amines toward
substrate 1a increases with increasing amine basicity for
the S-O bond fission process. A similar result has been
obtained for the corresponding reactions with 1b and 1c.
The effect of amine basicity on rates is illustrated in
Figure 1. The statistically corrected Brønsted-type plots
downward curvature, e.g., from a large slope (â2 ) 0.86-
0.94) to a small one (â1 ) 0.35-0.46) upon increasing the
amine basicity. Such a biphasic Brønsted-type plot sug-
gests that the reactions of 1a-c with these amines
(21) Bell, R. P. The Proton in Chemistry; Methuen: London, 1959;
p 159.
1440 J. Org. Chem., Vol. 70, No. 4, 2005

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
2,4-Dinitrophenyl X-Substituted Benzenesulfonates
TABLE 2. Summary of k2/k-1 Ratios for the S-O Bond
Fission in the Reaction of 1a-c with Primary Amines in
80 Mol % H2O/20 Mol % DMSO at 25.0 ( 0.1°C
proceed through an addition intermediate with a change
in the RDS.
The nonlinear Brønsted-type plots shown in Figure 1
have been analyzed using a semiempirical equation (eq
3)22 on the basis of the proposed mechanism shown in
Scheme 1. â1 and â2 represent the slope of the Brønsted-
type plots in Figure 1 for the reactions with strongly basic
k2/k-1
no.
amine
pKa
1a
1ba
12.6
16.2
1c
12.6
16.2
1. ethylamine
10.67 14.0
10.89 18.1
10.32 6.52
10.06 6.84
9.67 4.33
9.46 3.38
8.51 0.876
7.68 0.418
2. propylamine
3. ethylenediamine
4. glycine
and weakly basic amines, respectively. The kN° refers to
6.05
6.05
S-O
6.34
6.34
the kN
value at pKa° where k2/k-1 ) 1.
5. ethanolamine
6. benzylamine
7. glycylglycine
8. glycine ethyl ester
4.08
4.08
3.22
3.22
log(kNS-O/kN°) ) â2(pKa - pKa°) - log(1 + R)/2
where log R ) (â2 - â1)(pKa - pKa°)
0.880
0.433
0.327
0.880
0.433
0.327
9. 1,2-diaminopropane-H+ 7.13 0.312
(3)
10. trifluoroethylamine
5.70 0.0409 0.0463 0.0463
The â1 values determined are 0.35, 0.41, and 0.46,
while the â2 values are 0.86, 0.88, and 0.94 for the
reactions of 1a, 1b, and 1c, respectively. The magnitude
of â1 and â2 values for the present study increases as the
substituent X in the nonleaving group changes from an
EDG to an EWG. However, the â1 and â2 values obtained
in the present reactions are in agreement with those
reported in stepwise aminolyses of various types of
carbonyl and sulfonyl esters (e.g., â1 ) 0.3 ( 0.2 and
â2 ) 0.9 ( 0.2).1-4,11 Thus, one can suggest that the S-O
bond fission in the aminolysis of 1a-c proceeds through
a stepwise mechanism with a change in the RDS.
Effect of Nonleaving Group Substituent on pKa°
and k2/k-1 Ratio for S-O Bond Fission. The pKa°
value has been determined to be 8.9 ( 0.1 for the
reactions of 1a-c regardless of the substituent X, indi-
cating that the electronic nature of the substituent in the
nonleaving group does not affect the pKa° value signifi-
cantly in the present reactions. This contrasts with the
Jencks and Castro’s finding that an EWG in the non-
leaving group increases the pKa° value for aminolyses of
various esters.17-19 However, the present result is con-
sistent with our previous report that the pKa° value for
aminolysis of 2,4-dinitrophenyl X-substituted benzoates
is independent of the electronic nature of the substituent
X in the nonleaving group.20
a Data for the reaction of 1b were taken from ref 11a.
TABLE 3. Summary of k1 Values for the S-O Bond
Fission in the Reaction of 1a-c with Primary Amines in
80 Mol % H2O/20 Mol % DMSO at 25.0 ( 0.1°C
103 x k1 (M-1 s-1
)
no.
amine
pKa
1a
1ba
1c
1.
2.
3.
4.
5.
6.
7.
8.
9.
ethylamine
10.67
10.89
10.32
10.06
9.67
334
313
278
181
111
109
1390 11300
propylamine
1110
969
9140
6940
4430
2320
2400
545
ethylenediamine
glycine
643
ethanolamine
benzylamine
388
9.46
337
glycylglycine
8.51 34.7
7.68 24.9
7.13 22.2
5.70 4.81
93.3
63.3
51.6
10.6
glycine ethyl ester
331
1,2-diaminopropane-H+
321
10. trifluoroethylamine
42.0
a Data for the reaction of 1b were taken from ref 11a.
A similar result is obtained for reactions of 1b and 1c.
This is consistent with the preceding proposal that a
change in the RDS occurs at pKa ca. 8.9 for the reactions
of 1a-c.
The effect of amine basicity on the k2/k-1 ratio has been
illustrated in Figure 2. The statistically corrected Brøn-
sted-type plots for the reactions of 1a-c are linear with
a similar slope (e.g., - â-1 ) 0.50 ( 0.01). The k2 value
has been suggested to be independent of the amine
basicity.1a,23-25 On the other hand, the k-1 value would
decrease as the amine basicity increases since an amine
becomes a poorer nucleofuge with increasing its basicity.
Thus, one can suggest that the decreasing k-1 value is
mainly responsible for the increasing k2/k-1 ratio as the
basicity of amines increases.
Figure 2 demonstrates that the k2/k-1 ratio is almost
identical for the reactions of 1a-c. This result clearly
reconfirms our previous proposal that the electronic
nature of the substituent X in the nonleaving group does
not affect the k2/k-1 ratio significantly for aminolysis of
aryl X-substituted benzoates4a,20 and for alkaline hydroly-
sis of aryl X-substituted benzoates and thionobenzoates.12a,b
We have suggested that an EWG in the nonleaving
group would decrease both k2 and k-1 values since the
nucleofuge departs with the electron pair originally
bonded to the remainder of the intermediate.4a,12,20 On
the contrary, an EDG would increase both k2 and k-1
values.4a,12,20 Since the substituent effect on k2 and k-1
values would be in a parallel direction, one can suggest
kNS-O ) k1k2/(k-1 + k2)
) k1/(k-1/k2 + 1)
(4)
S-O
Dissection of the kN
value into its microscopic rate
constants is necessary to investigate the electronic effect
of the substituent X on the k2/k-1 ratio as well as pKa°
value for the present aminolysis of 1a-c. Since the
S-O
apparent second-order rate constant kN
can be ex-
pressed as eq 4 on the basis of the proposed mechanism
in Scheme 1, the k2/k-1 ratios associated with the ami-
nolysis of 1a-c have been determined by the method
described in Supporting Information (eqs S1-S6). The
S-O
k1 values have been determined from eq 4 using the kN
values in Table 1 and the k2/k-1 ratios determined above.
The k2/k-1 ratios and k1 values determined are sum-
marized in Tables 2 and 3, respectively.
As shown in Table 2, the k2/k-1 ratio increases as the
basicity of amines increases, i.e., k2/k-1 < 1 for pKa e 8.51
and k2/k-1 > 1 for pKa g 9.46 for the reactions of 1a.
(22) (a) Gresser, M. J.; Jencks, W. P. J. Am. Chem. Soc. 1977, 99,
6963-6970. (b) Castro, E. A.; Ureta, C. J. Org. Chem. 1989, 54, 2153-
2159.
J. Org. Chem, Vol. 70, No. 4, 2005 1441