Alkaline Hydrolysis of 4-Nitrophenyl X-Substituted-Benzoates Revisited: New Insights from Yukawa–Tsuno Equation

Full text of DOI:10.1002/bkcs.11000

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DOI: 10.1002/bkcs.11000
BULLETIN OF THE
Y.-H. Shin et al.
KOREAN CHEMICAL SOCIETY
Alkaline Hydrolysis of 4-Nitrophenyl X-Substituted-Benzoates
Revisited: New Insights from Yukawa–Tsuno Equation
Young-Hee Shin,† Ji-Sun Kang,‡ and Ik-Hwan Um§,
*
†Department of Chemistry, Seoul National University, Seoul 08826, Korea
‡Engineering Plastic R&T Solvey, Seoul 153-023, Korea
§Department of Chemistry, Ewha Womans University, Seoul 120-750, Korea. *E-mail: ihum@ewha.ac.kr
Received September 8, 2016, Accepted October 17, 2016, Published online November 17, 2016
Keywords: Alkaline hydrolysis, 4-Nitrophenyl benzoate, Reaction mechanism, Hammett plot, Yukawa–
Tsuno plot
Although numerous experimental and computational stud-
ies on hydrolysis of esters have been carried out, the reac-
tion mechanism is not clearly understood.1–12 We have
previously reported that alkaline hydrolysis of Y-substi-
tuted-phenyl benzenesulfonates (1, Y = 2,4-(NO2)2, 3,4-
(NO2)2, 4-Cl-2-NO2, 4-NO2, 4-CHO, 4-COMe, 3-COMe,
4-Cl) proceeds through a concerted mechanism based on a
linear Brønsted-type plot with βlg = −0.55 and an excellent
linear Yukawa–Tsuno plot with ρY = 1.83 and r = 0.52.5
In contrast, Babtie et al. have reported that alkaline hydrol-
ysis of 1 (Y = 3-F-4-NO2, 4-NO2, 4-CN, 3-NO2, 3-CN,
4-Cl, H, and 3,4-Me2) proceeds through a concerted mech-
anism when the leaving group is weakly basic (e.g., pKa <
8.5) but proceeds through a stepwise mechanism for the
reaction of substrates possessing a more basic leaving
group on the basis of a curved Brønsted-type plot.6 Their
quantum mechanics/molecular mechanics (QM/MM) calcu-
lations have also supported presence of a pentavalent inter-
mediate.6 However, Duarte et al. have recently shown that
correlation of the kinetic data reported by Babtie et al. with
σY constants results in a good linear Hammett plot.7 More-
over, the curved Brønsted-type plot reported by Babtie
et al. becomes linear (with moderately scattered points)
when three more experimental data are added (i.e., the
kinetic data for the reactions of pyridine-3-yl benzenesulfo-
nate, and its N-oxide and N-methylpyridinium derivatives).7
Besides, no evidence for a thermodynamically stable inter-
mediate has been found from computational studies using
HF/6-31++G* level of theory.7 Thus, Duarte et al. have
concluded that the reaction proceeds through a concerted
mechanism without changing the reaction mechanism.7
However, the corresponding reaction of O-Y-substituted-
phenyl O-phenyl thionocarbonates (3, a C S analogue of 2)
has been suggested to proceed through a stepwise mechan-
ism, in which expulsion of the leaving group occurs after
the rate-determining step (RDS), on the basis of the kinetic
result that σYo constants exhibit a much better Hammett cor-
relation than σY− constants.9 This demonstrates that the
nature of the electrophilic center (i.e., C O vs. C S) gov-
erns the reaction mechanism.
The nature of acyl group has also been reported to be an
important factor that determines the reaction mechan-
ism.10,11 Alkaline hydrolysis of Y-substituted-phenyl
benzoates (4) has been reported to proceed through a step-
wise mechanism, in which expulsion of the leaving group
occurs after the RDS, on the basis of the kinetic result that
σYo constants exhibits a much better Hammett correlation
than σY− constants.10 In contrast, the reaction of Y-substi-
tuted-phenyl picolinates (5) has been suggested to proceed
through a forced concerted mechanism on the basis of an
excellent linear Yukawa–Tsuno plot with ρY = 0.82 and
r = 0.72,11 indicating that modification of the acyl group
from benzoyl in 4 to picolinyl in 5 (or phenoxycarbonyl in
2) causes a change in the reaction mechanism.
Some years ago, we reported that alkaline hydrolysis of
4-nitrophenyl X-substituted benzoates (6a–k, Scheme 1)
proceeds through a stepwise mechanism with a change in
the RDS on the basis of a curved Hammett plot (i.e., con-
cave downward curvature).12 However, if the reaction pro-
ceeds through a stepwise mechanism, expulsion of the
leaving group should occur after the RDS regardless of the
electronic nature of the substituent X. This is because OH−
ion is significantly more basic and a much poorer nucleo-
fuge than 4-nitrophenoxide ion. Apparently, our previous
report based on the nonlinear Hammett plot for the reaction
of 6a–k was incorrect.
We have reported that alkaline hydrolysis of Y-substi-
tuted-phenyl phenyl carbonates (2) proceeds through a
forced concerted mechanism on the basis of a linear
Yukawa–Tsuno plot with ρY = 1.21 and r = 0.33.8
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Scheme 1. Alkaline hydrolysis of 4-nitrophenyl X-substituted
benzoates (6a–k).
Thus, we have revisited alkaline hydrolysis of 4-
nitrophenyl X-substituted benzoates (6a–k) to investigate
the cause of the nonlinear Hammett plot as well as the reac-
tion mechanism. We wish to report that the nonlinear Ham-
mett plot reported previously for the reactions of 6a–k is
not due to a change in the RDS but is caused by resonance
stabilization of the substrates possessing an electron-
donating group (EDG) on the fourth position of the benzoyl
moiety. The current study has also highlighted that one has
to be extremely careful in interpretation of a nonlinear
Hammett plot.
The second-order rate constants (kOH–) for the reac-
tions of 6a–k are summarized in Table 1 together with
those reported previously. As shown in Table 1, the
k
OH– values measured in this study are practically the
same as those reported previously within an experimen-
tal error range. The effect of the substituent X on reac-
tivity is illustrated in Figure 1. The Hammett plot
consists of two intersecting straight lines, i.e., the ρX
value decreases as the substituent X changes from EDGs
to electron-withdrawing groups (EWGs). Such nonlinear
Hammett plot has traditionally been interpreted as a
change in the RDS.13 In fact, we have previously
reported that the reaction of 6a–k proceeds through a
stepwise mechanism with a change in the RDS.12
Figure 1. Hammett plots for alkaline hydrolysis of 4-nitrophenyl
X-substituted-benzoates (6a–k) in 80 mol % H2O/20 mol %
DMSO at 25.0 ꢀ 0.1ꢁC.
However, as mentioned above, if the reaction proceeds
through a stepwise mechanism, expulsion of the leaving
group should occur after the RDS regardless of the elec-
tronic nature of the substituent X in the nonleaving group.
Thus, one might attribute the nonlinear Hammett plot to a
change in the reaction mechanism, e.g., from a stepwise
mechanism, in which expulsion of the leaving group occurs
after the RDS, to a concerted mechanism as the substituent
X changes from EWGs to EDGs. This idea can be sup-
ported by the report that modification of the acyl group
from benzoyl in 4 to picolinyl in 5 (or phenoxycarbonyl in
2) causes a change in the reaction mechanism from a step-
wise mechanism to a forced concerted pathway.8–11
However, we propose that the nonlinear Hammett plot
shown in Figure 1 is not due to a change in the reaction
mechanism based on the following reasons. Substrates pos-
sessing an EDG at the 4-position of the benzoyl moiety (e.
g., 6k) could be stabilized through resonance interactions
as illustrated by the resonance structures IR and IIR. It is
apparent that such resonance interaction could cause a
decrease in reactivity by stabilizing the ground state
(GS) of the substrate. In fact, a careful examination of the
nonlinear Hammett plot in Figure 1 reveals that substrates
bearing an EDG deviate negatively from the linear line
Table 1. Summary of second-order rate constants for alkaline
hydrolysis of 4-nitrophenyl X-substituted-benzoates (6a–k) in
80 mol % H2O/20 mol % DMSO at 25.0 ꢀ 0.1ꢁC.
X
k s
OH–/M−1 −1
6a
6b
6c
6d
6e
6f
6g
6h
6i
3,5-(NO2)2
4-Cl-3-NO2
4-NO2
4-CN
3-Cl
4-Cl
4960 ꢀ 140 (5010)
706 ꢀ 18 (715)
507 ꢀ 15 (531)
329 ꢀ 13 (354)
74.5 ꢀ 1.8 (73.8)
40.5 ꢀ 1.1 (39.6)
13.4 ꢀ 0.4 (13.4)
— (8.90)
5.96 ꢀ 0.20 (5.65)
2.91 ꢀ 0.08 (2.64)
0.156 ꢀ 0.005 (—)
H
3-CH3
4-CH3
4-OCH3
4-N(CH3)2
6j
6k
The data in the parenthesis are taken from Ref. 12.
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KOREAN CHEMICAL SOCIETY
composed with substrates holding an EWG (i.e., 6a–f). Fur-
thermore, such negative deviation is more significant for
the substrate possessing a stronger EDG (e.g., 6k). Thus,
we propose that the nonlinear Hammett plot is caused by
resonance stabilization of the GS of the substrates posses-
sing an EDG in the benzoyl moiety.
O
O
Me
Me
Me
Me
N
C OAr
N
C OAr
IR
IIR
To examine the validity of the above proposal, Yukawa–
Tsuno plot has been constructed using the kinetic data in
Table 1. Although the Yukawa–Tsuno equation (Eq. (1)) was
derived to account for the experimental results for solvolysis
of benzylic system,14,15 we have shown that Eq. (1) is highly
effective in deduction of the reaction mechanism for various
nucleophilic substitution reactions of various esters.16
+
o
logkX=kH = ρX½σXo + rðσX – σX Þꢂ
ð1Þ
As shown in Figure 2, the Yukawa–Tsuno plot exhibits
an excellent linear correlation (R2 = 0.998) with ρX = 1.83
and r = 0.50. This indicates that the nonlinear Hammett
plot for the reaction of 6a–k is clearly not due to a change
in the RDS (or reaction mechanism). It is noted that the r-
value in Eq. (1) represents extent of the resonance contribu-
tion.14,15 Thus, an r-value of 0.50 found in this study is
consistent with our proposal that resonance stabilization of
the substrate possessing an EDG in the benzoyl moiety is
responsible for the negative deviation from the linear Ham-
mett plot composed with the substrates possessing an EWG
in the benzoyl moiety (e.g., 6a–f).
Many factors have been reported to influence the magni-
tude of the ρX value (e.g., the charge type and basicity of
nucleophiles, the distance from the reaction center to the
substituent, the nature of the reaction mechanism, etc.).16,17
One might expect a large ρX value for reactions which pro-
ceed through a stepwise pathway with expulsion of the leav-
ing group occurring after the RDS. Because electrophilicity
of the reaction center would be increased by an EWG in the
benzoyl moiety but decreased by an EDG. In contrast, a
small ρX value would be expected for reactions that proceed
through a concerted mechanism or via a stepwise pathway
with expulsion of the leaving group occurring in the RDS.
Because an EWG in the benzoyl moiety would accelerate
rate of the nucleophilic attack but would retard rate of the
leaving-group expulsion. In fact, a small ρX value (e.g.,
ρX < 1) has often been reported for reactions that proceed
through a concerted mechanism.17 Thus, a ρX value of 1.83
found in this study is quite large and is consistent with our
previous report that alkaline hydrolysis of Y-substituted-
phenyl benzoates proceed through a stepwise mechanism
with formation of an addition intermediate being the RDS.
Figure 2. Yukawa–Tsuno plot for alkaline hydrolysis of 4-
nitrophenyl X-substituted-benzoates (6a–k) in 80 mol % H2O/
20 mol % DMSO at 25.0 ꢀ 0.1ꢁC.
In summary, although the Hammett plot for the alkaline
hydrolysis of 6a–k consists of two intersecting straight lines,
the Yukawa–Tsuno plot exhibits an excellent linear correla-
tion with ρX = 1.83 and r = 0.50. Thus, the nonlinear Ham-
mett plot is clearly not due to a change in the RDS (or the
reaction mechanism) but is caused by resonance stabilization
of the substrates bearing an EDG in the benzoyl moiety. The
large ρX value found for the current reaction is consistent
with the previous report that alkaline hydrolysis of Y-substi-
tuted-phenyl benzoates (4) proceeds through a stepwise
mechanism with formation of an addition intermediate being
the RDS. The current study has also demonstrated that
deduction of the reaction mechanism based just on a linear or
nonlinear Hammett plot could lead a wrong conclusion.
Experimental
Materials. Compounds 6a–k were readily prepared from
the reaction of X-substituted-benzoyl chloride and 4-
nitrophenol in anhydrous ether in the presence of triethyla-
mine as reported previously.10 Their purity was confirmed
1
from melting points and H NMR characteristics. Doubly
glass distilled H2O was further boiled and cooled under
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BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
(b) J. M. Younker, A. C. Hengge, J. Org. Chem. 2004,
69, 9043.
nitrogen atmosphere just before use. NaOH stock solution
was titrated using potassium hydrogen phthalate. Dimethyl
sulfoxide (DMSO) and other chemicals used were of the
highest quality available.
Kinetics. The kinetic study was performed using a UV–
Vis spectrophotometer for slow reactions (t1/2 > 10 s) or a
stopped-flow spectrophotometer for fast reactions (t1/
4. (a) V. Nummert, M. Piirsalu, I. A. Koppel, Cent. Eur.
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≤ 10 s) equipped with a constant temperature circulating
2
bath to keep the reaction temperature at 25.0 ꢀ 0.1ꢁC. All
reactions in this study were carried out under pseudo-first-
order conditions in which NaOH concentration was at least
20 times greater than the substrate concentration. The reac-
tions were followed by monitoring the appearance of 4-
nitrophenoxide ion up to nine half-lives. The plots of the
pseudo-first-order rate constants (kobsd) vs. [OH−] were lin-
ear and passed through the origin, indicating that contribu-
tion of H2O to kobsd is negligible. Thus, second-order rate
constants (kOH–) were calculated from the slope of linear
plots and summarized in Table 1.
Product Analysis. 4-Nitrophenoxide ion was liberated
quantitatively and identified as one of the reaction products
by comparison of the UV–Vis spectra obtained after com-
pletion of the reactions with those of authentic samples
under the same kinetic conditions.
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Chem. Soc. 2010, 31, 2015.
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2011, 32, 179.
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Chem. 2002, 67, 8475.
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Acknowledgments. This research was supported by Basic
Science Research Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Edu-
cation (2015-R1D1A1A-01059624).
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