Reactions of aryl acetates with secondary alicyclic amines in ethanol/water mixtures: Effect of the solvent composition on the kinetics and mechanism

Article abstract of DOI:10.1002/kin.20598

We report a kinetic study on the reactions of secondary alicyclic amines toward 4-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-trinitrophenyl acetates (1, 2, and 3) in ethanol/water mixtures of different compositions. It is found that (i) the intermediate in the reaction of 1 is stabilized in a mixture of 90 vol% ethanol; (ii) for the reaction of 2, the mechanism is stepwise in water but concerted in the mixtures; (iii) For the reaction of 3, the mechanism is concerted along the whole range of composition; (iv) the effect of -NO ₂ outweighs the solvent effect; (v) preferential solvation in the core of reaction can be ruled out.

Full text of DOI:10.1002/kin.20598

Reactions of Aryl Acetates
with Secondary Alicyclic
Amines in Ethanol/Water
Mixtures: Effect of the
Solvent Composition on the
Kinetics and Mechanism
1
1
1
2
´
ENRIQUE A. CASTRO, DANIELA MILLAN, RAUL AGUAYO, PAOLA R. CAMPODONICO,
1
´
JOSE G. SANTOS
1Facultad de Qu´ımica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 609-4411, Chile
2Instituto de Ciencias, Facultad de Medicina, Cl´ınica Alemana Universidad del Desarrollo, Santiago 771-0162, Chile
Received 12 May 2011; revised 12 July 2011; accepted 14 July 2011
DOI 10.1002/kin.20598
Published online 2 September 2011 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: We report a kinetic study on the reactions of secondary alicyclic amines toward
4-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-trinitrophenyl acetates (1, 2, and 3) in ethanol/water
mixtures of different compositions. It is found that (i) the intermediate in the reaction of 1 is
stabilized in a mixture of 90 vol% ethanol; (ii) for the reaction of 2, the mechanism is stepwise
in water but concerted in the mixtures; (iii) For the reaction of 3, the mechanism is concerted
along the whole range of composition; (iv) the effect of NO2 outweighs the solvent effect;
(v) preferential solvation in the core of reaction can be ruled out. ꢀ 2011 Wiley Periodicals, Inc.
C
Int J Chem Kinet 43: 687–693, 2011
these processes [1–31]. Aryl esters are compounds
that depending on the nature of the nucleophile, the
leaving group, and other factors can react by two
possible mechanisms: (i) A concerted pathway [7–
14], where the nucleophile attack at the electrophilic
carbon in the carbonyl group occurs simultaneously
with the leaving group departure within a single step.
(ii) A stepwise mechanism where the interaction of
the nucleophile with the electrophilic carbon may lead
to the formation of a tetrahedral intermediate, T ,
from which the leaving group detaches [1–11,15–31].
In these reactions, as well as in other related ones,
several factors have been described as affecting the
INTRODUCTION
The aminolysis reactions of aryl esters in solution
have been studied by several groups, and there is now
considerable data on the kinetics and mechanisms of
Correspondence to: J. G. Santos; e-mail: jgsantos@uc.cl.
Contract grant sponsor: MECESUP of Chile.
Contract grant numbers: PUC-0004 and RED QUIMICA
UCH-0601.
Contract grant sponsor: FONDECYT of Chile.
Contract grant number: 1095145.
Supporting Information is available in the online issue at
www.wileyonlinelibrary.com.
c
ꢀ
2011 Wiley Periodicals, Inc.

688
CASTRO ET AL.
X
Determination of pKa
O
The pKa values for the conjugate acids of the SA
amines in different aqueous/ethanol mixtures were de-
termined potentiometrically by the reported method
[50]. The experimental conditions used were the same
as those used for the kinetic measurements (see be-
low). The pKa values obtained for the conjugate
acids of amines, under these conditions, are shown in
Table I.
Me
C
O
NO2
Y
1 X = Y = H
2 X = H; Y = NO2
3 X = Y = NO2
Figure 1 General structures of the aryl acetates considered
in this study.
Kinetic Measurements
kinetics and mechanisms, such as nucleophile nature
[12,13,15,16,32–34], leaving-group ability (nucleofu-
gality) [14–31,35–38], nonleaving-group effect [22–
24,39,40], nucleophile–electrophile interaction [41],
and solvent effects [14,42–47]. Most of these works in-
volve experimental investigations, and there have also
been theoretical studies of these factors [14,27,48].
However, concerning the solvent effects on the kinetics
and mechanisms, there have been no systematic studies
in the literature but only scattered results [14,42–47].
Therefore, the solvent effects in acylation reactions
have not been completely documented up to date. Our
group has systematically studied the aminolysis of aryl
esters in both aqueous solution [17–21,34] and 44 wt%
ethanol/water [22–24]. On the contrary, other groups
have been studying acylation reactions in pure organic
solvents, such as acetonitrile, dimethylsulfoxide, and
also in their aqueous mixtures [25,26,28–31,42–47].
Based on these results, it is possible to argue that the
interactions between solvent and intermediate T , re-
actants, and transition state (TS) change the reaction
mechanism [25,26,28–31,34].
In this work, we report on the kinetics of the re-
actions of 4-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-
trinitrophenyl acetates (1, 2, and 3, respectively; see
Fig. 1) with a series of secondary alicyclic (SA) amines
in ethanol/water mixtures of different compositions.
The aim of this study is twofold: First, the kinetic mea-
surements are used to obtain Brønsted-type plots (log
of rate coefficients vs. pKa values) and gain useful
information about the reaction mechanism. A second
goal of this work is to investigate the effects of the
solvent and the nucleofuge nature on the kinetics and
reaction mechanism.
The kinetics of the reactions was measured through
a diode-array spectrophotometer (at the 300–500 nm
wavelength range) in different ethanol/water mixtures
at 25.0 0.1◦C and an ionic strength of 0.2 M (main-
tained with KCl). The reactions were studied under at
least 10-fold amine excess over the substrate, the ini-
tial concentration being 2.5 × 10−5 M. Under these
conditions, pseudo-first-order rate coefficients (kobs
)
were found throughout, the reactions being followed
for at least five half-lives by the absorbance increase
at the wavelength corresponding to 4-nitrophenoxide
(400 nm), 2,4-dinitrophenoxide (350 nm), or 2,4,6-
trinitrophenoxide (350 nm) anions. For all the reac-
tions, the pH was maintained constant by the buffer
formed by partial protonation of the nucleophile or by
addition of an external buffer. Some of the reactions
with piperazine and piperazinium ion were studied at
several pH values, where mixtures of both amines are
present. In these cases, the kN values were obtained
through Eqs. (1) and (2). In these equations, kNobs is
an overall nucleophilic rate constant (corresponding to
the mixture of nucleophiles), [N]tot is the total piper-
azine (piperazine + piperazinium ion) concentration,
FN and FNH are the molar fractions of piperazine and
piperazinium ion, respectively, and kN and kNH are
their corresponding nucleophilic rate constants. The
values of kNobs were obtained as the slopes of linear
plots of kobs vs. [N]tot at constant pH. The nucleophilic
rate constants for the reactions with piperazine (kN)
and piperazinium ion (kNH) were determined through
Eq. (2), as described [51].
kobs = k0 + kNobs[N]tot
kNobs = FN kN + FNH kNH
(1)
(2)
EXPERIMENTAL
Materials
Reaction Product Studies
SA amines were purified by recrystallization or distil-
lation. Acetates 1, 2, and 3 were prepared as described
[49].
For the reactions of 1, 2 and 3, one of the products was
identified as 4-nitrophenoxide, 2,4-dinitrophenoxide,
and 2,4,6-trinitrophenoxide anions, respectively. This
International Journal of Chemical Kinetics DOI 10.1002/kin

REACTIONS OF ARYL ACETATES WITH ALICYCLIC AMINES
689
Table I Values of pKa for the Conjugate Acids of SA Amines and kN Values for the Reactions of SA Amines with
Acetates 1, 2, and 3 in Different Aqueous/Ethanol Mixturesa
Substrate
Ethanol (Vol%)
90
SA Amine
pK
kN/(s−1 M−1
)
a
1
Piperidine
Piperazine
1-(2-Hydroxyethyl)piperazine
Morpholine
1-Formylpiperazine
Piperidine
Piperazine
1-(2-Hydroxyethyl)piperazine
Morpholine
1-Formylpiperazine
Piperazinium ion
Morpholine
10.0
9.13
2.50
0.82
0.20
0.075
0.0086
15.9
3.20
0.636
0.253
0.041
0.000222
16.6
194
8.65
7.98
6.96
11.02
9.86
9.16
8.56
7.71
5.41
8.23
10.82
9.71
9.09
8.48
7.63
5.37
11.02
9.86
9.16
8.56
7.71
5.41
11.15
9.90
9.29
8.71
7.57
6.65
10.82
9.71
9.09
8.48
7.63
5.37
1
25
2
2
75
50
Piperidine
Piperazine
129
1-(2-Hydroxyethyl)piperazine
Morpholine
1-Formylpiperazine
Piperazinium ion
Piperidine
Piperazine
1-(2-Hydroxyethyl)piperazine
Morpholine
1-Formylpiperazine
Piperazinium ion
Piperidine
Piperazine
1-(2-Hydroxyethyl)piperazine
Morpholine
1-Formylpiperazine
Piperazinium ion
Piperidine
Piperazine
1-(2-Hydroxyethyl)piperazine
Morpholine
38.0
30.0
6.0
0.67
423
2
2
3
25
10
50
275
72.2
39.8
9.13
0.84
789
275
110
70.3
15.3
0.879
1814
1241
129
214
29.8
3.5
1-Formylpiperazine
Piperazinium ion
a Both pKa and kN values were obtained in the corresponding ethanol/water mixture, at 25.0 0.1◦C and an ionic strength of 0.2 M.
was achieved by comparison of the UV–vis spectra
after completion of the reactions with those of the au-
thentic samples of the corresponding phenoxide ions
under the same experimental conditions.
showed no dependence on pH within the pH range
employed. These values were obtained as the inter-
cept and slope, respectively, of linear plots of kobs
against the free amine concentration (Eq. (3)) at con-
stant pH. The experimental conditions, the amine con-
centration, and kobs values for the studied reactions
are shown in Tables S-1 to S-32 in the Supporting
Information.
RESULTS AND DISCUSSION
kobs = k0 + kN [free amine]
(3)
The kinetics of all the studied reactions obeyed Eq. (3),
where k0 and kN are the rate coefficients for solvoly-
sis (ethanolysis and/or hydrolysis) and aminolysis of
the substrates, respectively. The values of k0 and kN
The k0 values were much smaller than those of the kN
[free amine] term in Eq. (3). The values of kN for the
International Journal of Chemical Kinetics DOI 10.1002/kin

690
CASTRO ET AL.
reactions of acetates 1, 2, and 3 with SA amines in dif-
ferent aqueous/ethanol mixtures are shown in Table I.
With the kN and pKa data of Table I, the statisti-
cally corrected Brønsted-type plots (log kN/q vs. pKa +
log(p/q)) were obtained with q = 2 for piperazine (q =
1 for all other amines) and p = 2 for all conjugate acids
of the amines, except for the piperazinium ion with
p = 4. The parameter q is the number of equivalent ba-
sic sites on the free amine, and p is the number of equiv-
alent dissociable protons on the conjugate acid of the
amine [12,13,52]. These plots are shown in Figs. S1–
S6 in the Supporting Information. The Brønsted-type
plots obtained in different aqueous/ethanol mixtures
are linear with slopes, β = 0.8 and 0.9 for the reac-
tions of 1 at 90 and 25 vol% ethanol, respectively, and
β = 0.49–0.54 for the reactions of 2 and 3 at 10–50
vol% ethanol. The values of the Brønsted slopes for
the reactions of 1 are in accordance with a stepwise
mechanism where breakdown to products of a tetrahe-
dral intermediate is the rate-determining step. In these
cases, the slope values usually vary between 0.8 and
1.1 [1–11,15–25,53,54]. On the contrary, the magni-
tude of the slopes for the reactions of acetates 2 and 3
is in accordance with a concerted mechanism, which
usually exhibits slope values of 0.4–0.7 [7–14,32,33].
The β value measures the effective charge develop-
ment from reactants to the TS. For stepwise reactions,
the amino moiety in the TS for the second step has a
full positive charge (full C–N bond formation), and in
concerted reactions this charge is smaller (partial C–N
bond formation). This is why for the former mecha-
nism β is near unity, whereas for a concerted process,
β is smaller than unity.
are the reported values for the reactions in water
[13,15,20].
The following three important observations can be
drawn from Table II:
1. The reactions of 1 with SA amines proceed by
a stepwise mechanism through a zwitterionic
tetrahedral intermediate (T ), as that shown in
Scheme 1, regardless of the aqueous ethanol
composition. According to the Brønsted slopes
found, expulsion of 4-nitrophenoxide from the
T
intermediate is the rate-determining step.
Therefore, it can be concluded that the T inter-
mediate is stabilized even in the 90 vol% ethanol
mixture.
2. The SA aminolysis of 2 is stepwise in water,
but concerted in aqueous ethanol mixtures. The
concerted process is shown in Scheme 2 (with
X = H).
3. The reactions of 3 with SA amines are governed
by a concerted mechanism, as that of Scheme 2
(X = NO2), in the whole range of the solvent
mixtures studied.
The incorporation of a second NO2 group in the
nucleofuge of the substrate (compound 2) does not
change the stepwise mechanism in water solution, but
the incorporation of a third NO2 group (compound 3)
in this solvent destabilizes the T intermediate, chang-
ing the mechanism to a concerted one [13]. Never-
theless, in 10 vol% ethanol, the incorporation of the
second nitro group is sufficient to destabilize the T
intermediate. This fact can be attributed to the decreas-
ing stability of the intermediate due to not only the
Table II shows the β values and the mechanisms
associated with the studied reactions. Also included
O–
O
C
O
k1
k2
Me
O
NO2
Me
C
O
NO2
Me
C
–O
NO2
+
+ NH
k–1
+ NH
+
NH
T
–H+ Fast
O
Me
C
N
Scheme 1 Stepwise reaction mechanism for the acetylation reactions of SA amines with compound 1 in different aqueous/
ethanol mixtures.
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REACTIONS OF ARYL ACETATES WITH ALICYCLIC AMINES
691
Table II Values of Brønsted Slopes (β) and Associated Mechanisms (Concerted or Stepwise) for the Reactions of 1,
2, and 3 with SA Amines in Different Aqueous Ethanol Mixturesa
β Values and Associated Reaction Mechanisms in Ethanol (Vol%)
Substrate
0
10
25
50
90
1
2
3
0.82 stepwise [15]
0.2 and 0.85 stepwise [20]
0.41 concerted [13]
0.91 stepwise
0.50 concerted
0.81 stepwise
0.54 concerted
0.49 concerted
0.52 concerted
a β values determined in this work, unless otherwise stated.
electron-withdrawing ability of the NO2 group in the
aromatic ring, leading to a greater nucleofugality but
also the effect of the less polar solvent [54]. Another
destabilizing factor is the increase in the amine nucle-
ofugality from the T intermediate by the change in
solvent from water to aqueous ethanol. It is known that
in the aminolysis of esters and diaryl carbonates the
amine is expelled faster from the T intermediate by
the change to a less polar solvent [54]. Note that for
acetate 2, the change in solvent from water to aqueous
10 vol% ethanol destabilizes the tetrahedral intermedi-
ate as well as the incorporation of a third nitro group.
Table I shows that for compounds 1 and 2 the kN val-
ues increase in accordance with the percentage of water
in the solvent mixture. On the basis of this observation,
we can conclude that the global solvent composition (in
the bulk) is the same as that in the solvation shell in the
reaction center. This rules out a preferential solvation
behavior.
2.0
1.5
1.0
0.5
54.0
54.5
55.0
55.5
ET(30)
Figure 2 Relationships between log kN/q values and the ET
(30) parameter for the reactions of compound 2 with mor-
pholine ( ) and 1-formylpiperazine ( ) in different aqueous/
•
◦
ethanol solvents.
Figure 2 shows the relationship between log kN and
the polarity ET (30) parameter for the reactions of com-
pound 2 with morpholine and 1-formylpiperazine. The
latter was determined using Langhals equation [55] for
different vol% of ethanol in the studied mixtures.
In these cases, linear plots with positive slopes are
observed, which can be explained by a greater stabi-
lization of the TS (of the concerted pathway), with
respect to reactants, as the solvent mixture becomes
more aqueous. It is reasonable that in water media, the
putative tetrahedral intermediate would be stabilized
favoring the stepwise mechanism.
X
X
O
C
O
C
kN
Me
O
NO2
Me
–O
NO2
+
+ NH
+
O2N
O2N
NH
–H+ Fast
CONCLUSIONS
2 X = H
3 X = NO2
The acetylation reactions of a series of aryl acetates
toward SA amines are kinetically studied in several
aqueous ethanol mixtures. The kinetic data for the re-
actions of compound 1 are consistent with a stepwise
mechanism, with breakdown to products of the tetra-
hedral intermediate as the rate-determining step for
the whole range of solvent mixtures studied. On the
O
Me
C
N
Scheme 2 Concerted reaction mechanism for the acety-
lation reactions of SA amines with compounds 2 and 3 in
different ethanol aqueous mixtures.
International Journal of Chemical Kinetics DOI 10.1002/kin

692
CASTRO ET AL.
contrary, for the reactions of compounds 2 and 3 the ki-
netic results are in accordance with a concerted mech-
anism. From the analysis of the solvent effects on the
reaction mechanisms, it is found that (i) for the SA
aminolysis of acetate 1, the tetrahedral intermediate
is relatively stable even in 90 vol% ethanol; (ii) the
aminolysis of compound 2 is stepwise in water, but
concerted in the aqueous/ethanol mixtures studied; (iii)
for the aminolysis of compound 2, the change of sol-
vent from water to aqueous 10 vol% ethanol, as well as
the incorporation of a third nitro group, destabilizes the
tetrahedral intermediate; (iv) a change of solvent mix-
ture does not change the mechanism of the aminolysis
of acetate 3; and (v) preferential solvation in the core of
the reaction can be ruled out for the SA aminolysis of
compound 2.
19. Castro, E. A.; Borquez, M. T.; Parada, P. M. J Org Chem
1986, 51, 5072–5077.
20. Castro, E. A.; Ureta, C. J Org Chem 1990, 55, 1676–
1679.
21. Castro, E. A.; Iban˜ez, F.; Lagos, S.; Schick, M.; Santos,
J. G. J Org Chem 1992, 57, 2691–2694.
22. Castro, E. A.; Steinfort, G. B. J Chem Soc, Perkin Trans
2 1983, 453–457.
23. Castro, E. A.; Santander, C. L. J Org Chem 1985, 50,
3595–3600.
24. Castro, E. A.; Valdivia, J. L. J Org Chem 1986, 51,
1668–1672.
25. Lee, H. W.; Yun, Y. S.; Lee, B. S.; Koh, H. J.; Lee, I.
J Chem Soc, Perkin Trans 2 2000, 2302–2306.
26. Lee, I.; Sung, D. D. Curr Org Chem 2004, 8, 557–
567.
27. Galabov, B.; Ilieva, S.; Hadjieva, B.; Atanasov, Y.;
Schaefer, H. F., III J Phys Chem A 2008, 112, 6700–
6707.
28. Um, I. H.; Min, J. S.; Lee, H. W. Can J Chem 1999, 77,
659–666.
DM thanks CONICYT of Chile for a doctoral fellowship.
29. Um, I. H.; Min, J. S.; Ahn, J. A.; Hahn, H. J. J Org Chem
2000, 65, 5659–5663.
30. Um, I. H.; Han, H. J.; Ahn, J. A.; Kang, S.; Buncel, E.
J Org Chem 2002, 67, 8475–8480.
BIBLIOGRAPHY
1. Johnson, S. L. Adv Phys Org Chem 1967, 5, 237–330.
2. Bruice, T. C.; Jencks, W. P. Catalysis in Chemistry and
Enzymology; McGraw-Hill: New York, 1969; pp. 480–
485.
31. Um, I. H.; Kim, K. H.; Park, H. R.; Fujio, M.; Tsuno, Y.
J Org Chem 2004, 69, 3937–3942.
32. Castro, E. A.; Pavez, P.; Santos, J. G. J Org Chem 2003,
68, 3640–3645.
3. Johnson C. D. Chem Rev 1975, 75, 755–765.
4. Kirby, A. J. Organic Reaction Mechanisms; Knipe,
A. C.; Watts, W. E., Eds.; Wiley: New York, 1980;
pp. 29–83.
5. Jencks, W. P. Chem Soc Rev 1981, 10, 345–375.
6. Marlier, J. F. Acc Chem Res 2001, 34, 283–290.
7. Page, M. I.; Williams, A. Organic & Bio-organic Mech-
anisms; Longman: Harlow, UK, 1997; Ch. 7, pp. 33–36.
8. Williams, A. Concerted Organic and Bio-organic Mech-
anisms; CRC Press: Boca Raton, FL, 2000; Ch. 4,
pp. 43–46.
9. Carroll, F. A. Perspectives on Structure and Mechanism
in Organic Chemistry; Brooks/Cole: Pacific Grove, CA,
1998; pp. 434–448.
10. Williams, A. Adv Phys Org Chem 1992, 27, 1–55.
11. Williams, A. Chem Soc Rev 1994, 23, 93–100.
12. Castro, E. A.; Hormazabal, A.; Santos, J. G. Int J Chem
Kinet 1998, 30, 267–272.
33. Castro, E. A.; Aliaga, M.; Santos, J. G. J Phys Org Chem
2008, 21, 271–278.
34. Campodo´nico, P. R.; Aliaga, M. E.; Santos, J. G.; Castro,
E. A.; Contreras, R. Chem Phys Lett 2010, 488, 86–89.
35. Campodo´nico, P. R.; Aizman, A.; Contreras, R. Chem
Phys Lett 2006, 422, 340–344.
36. Campodo´nico, P. R.; Aizman, A.; Andre´s, J.; Contreras,
R. Chem Phys Lett 2007, 439, 177–182.
37. Campodo´nico, P. R.; Pe´rez, C.; Aliaga, M.; Gazitu´a, M.;
Contreras, R. Chem Phys Lett 2007, 447, 375–378.
38. Castro, E. A.; Aliaga, M.; Campodonico, P. R.; Cepeda,
M; Contreras, R.; Santos, J. G. J Org Chem 2009, 74,
9173–9179.
39. Campodo´nico, P. R.; Ormazabal-Toledo, R.; Aizman,
A.; Contreras, R. Chem Phys Lett 2010, 498, 221–
225.
40. Castro, E. A.; Ramos, M.; Santos, J. G. J Org Chem
2009, 74, 6374–6377.
13. Castro, E. A.; Cubillos, M.; Santos, J. G. J Org Chem
2001, 66, 6000–6003.
14. Yi, G.-Q.; Zeng, Y.; Xia, X.-F.; Xue, Y.; Kim, C.-K.;
Yan, G.-S. Chem Phys 2008, 345, 73–81.
15. Jencks, W. P.; Gilchrist, M. J Am Chem Soc 1968, 90,
2622–2637.
41. Campodo´nico, P. R.; Santos, J. G.; Andre´s, J.; Contreras,
R. J Phys Org Chem 2004, 17, 273–281.
42. Kevill, D. N.; D’Souza, M. J. Can J Chem 1999, 77,
1118–1122.
43. Oh, H. K.; Ha, J. S.; Sung, D. D.; Lee, I. J Org Chem
2004, 69, 8219–8223.
16. Satterthwait, A. C.; Jencks, W. P. J Am Chem Soc 1974,
96, 7018–7031.
44. Oh, H. K.; Lee, J. M.; Lee, H. W.; Lee, I. Int J Chem
Kinet 2004, 36, 434–440.
17. Bond, P. M.; Castro, E. A.; Moodie, R. B. J Chem Soc,
Perkin Trans 2 1976, 68–72.
45. Sung, D. D.; Han, I. S.; Lee, I. J Sulfur Chem 2007, 28,
483–491.
18. Castro, E. A.; Freudenberg, M. J Org Chem 1980, 45,
906–910.
46. Um, I.-H.; Kim, E. Y.; Park, H.-R.; Jeon, S.-E. J Org
Chem 2006, 71, 2302–2306.
International Journal of Chemical Kinetics DOI 10.1002/kin

REACTIONS OF ARYL ACETATES WITH ALICYCLIC AMINES
693
47. Um, I.-H.; Park, Y.-M.; Fujio, M.; Mishima, M.; Tsuno,
Y. J Org Chem 2007, 72, 4816–4821.
51. Castro, E. A.; Ureta, C. J Org Chem 1989, 54, 2153–
2159.
48. Lee, I.; Kim, C. K.; Li, H. G.; Sohn, C. K.; Kim,
C. K.; Lee, H. W.; Lee, B. S. J Am Chem Soc 2000,
122, 11162–11172.
52. Bell, R. P. The Proton in Chemistry; Methuen: London,
1959; p. 159.
53. Gresser, M. J.; Jencks, W. P. J Am Chem Soc 1977, 99,
49. Kirkien-Konasiewics, A.; Maccoll, A. J Chem Soc 1964,
1267–1274.
6963–6970.
54. Gresser, M. J.; Jencks, W. P. J Am Chem Soc 1977, 99,
50. Albert, A.; Serjeant, E. P. The Determination of Ion-
ization Constants; Chapman and Hall: London, 1971;
p. 9.
6970–6980.
55. Langhals, H. Angew Chem, Int Ed Engl 1982, 21, 724–
733.
International Journal of Chemical Kinetics DOI 10.1002/kin