Alkali-metal ion catalysis and inhibition in nucleophilic displacement reaction of O-ethyl O-4-nitrophenyl phenylphosphonothioate with alkali-metal ethoxides

Article abstract of DOI:10.1246/bcsj.20130015

A kinetic study on nucleophilic displacement reactions of O-ethyl O-4-nitrophenyl phenylphosphonothioate (an insecticide called EPN) with alkali-metal ethoxides (EtOM; M = Li, Na, K, and K/18-crown-6-ether) is reported. Dissection of pseudo-first-order rate constant (k_obsd) into the second-order rate constants for the reaction of EPN with the dissociated EtO^- (k_EtO-) and ion-paired EtOM (k_EtOM) has revealed that the reactivity increases in the order k_EtOLi < k_EtO < k_EtONa < k_EtOK < k _{EtOK/18-crown-6-ether}, indicating that Li⁺ inhibits the reaction while the other M⁺ ions behave as a Lewis acid catalyst in the order Na⁺ < K⁺ < 18C6-complexed K⁺. The contrasting M⁺ ion effects have been explained in terms of the hard and soft acids and bases (HSAB) principle, since EPN, as a polarizable P=S centered electrophile, would exert a weak interaction with Li⁺ (a hard acid) but a strong interaction with the 18C6-complexed K⁺ ion (a soft acid). M⁺ ions catalyze the current reaction by increasing the electrophilicity of the reaction center. EPN is less reactive than O-4-nitrophenyl diphenylphosphinothioate but is more reactive than O-4-nitrophenyl O,O-diethyl thiophosphate. Factors governing the reactivity of these P=S centered electrophiles are discussed.

Full text of DOI:10.1246/bcsj.20130015

736
Bull. Chem. Soc. Jpn. Vol. 86, No. 6, 736-741 (2013)
© 2013 The Chemical Society of Japan
Alkali-Metal Ion Catalysis and Inhibition in Nucleophilic
Displacement Reaction of O-Ethyl O-4-Nitrophenyl
Phenylphosphonothioate with Alkali-Metal Ethoxides
Ik-Hwan Um,*1 Ji-Sun Kang,1 and Minah Shin2
1Department of Chemistry and Nano Sciences, Ewha Womans University, Seoul 120-750, Korea
2Hana Academy Seoul, Seoul 122-200, Korea
Received January 21, 2013; E-mail: ihum@ewha.ac.kr
A kinetic study on nucleophilic displacement reactions of O-ethyl O-4-nitrophenyl phenylphosphonothioate
(an insecticide called EPN) with alkali-metal ethoxides (EtOM; M = Li, Na, K, and K/18-crown-6-ether) is reported.
Dissection of pseudo-first-order rate constant (kobsd) into the second-order rate constants for the reaction of EPN with the
¹
ꢀ
dissociated EtO (kEtO ) and ion-paired EtOM (kEtOM) has revealed that the reactivity increases in the order kEtOLi
<
kEtO < kEtONa < kEtOK < kEtOK/18-crown-6-ether, indicating that Li+ inhibits the reaction while the other M+ ions behave as
a Lewis acid catalyst in the order Na+ < K+ < 18C6-complexed K+. The contrasting M+ ion effects have been explained
in terms of the hard and soft acids and bases (HSAB) principle, since EPN, as a polarizable P=S centered electrophile,
would exert a weak interaction with Li+ (a hard acid) but a strong interaction with the 18C6-complexed K+ ion (a soft
acid). M+ ions catalyze the current reaction by increasing the electrophilicity of the reaction center. EPN is less reactive
than O-4-nitrophenyl diphenylphosphinothioate but is more reactive than O-4-nitrophenyl O,O-diethyl thiophosphate.
Factors governing the reactivity of these P=S centered electrophiles are discussed.
ꢀ
Metal ions have often been reported to catalyze various
acyl-group transfer reactions as a Lewis acid catalyst.1-9 Since
Lewis acidity increases with increasing the charge density
of metal ions, most studies have focused on the reactions
X
EtO P O
OEt
X
Ph P O
Ph
NO2
NO2
involving multivalent metal ions (e.g., Mg2+, Mn2+, Zn2+
,
X = O (1), S (2)
X = O (3), S (4)
La3+, Eu3+, Co3+, etc.).1,2 Alkali-metal ions are ubiquitous
in nature and are known to play important roles in biological
processes (e.g., a Na+ pump which functions to keep high
K+ and low Na+ concentration in mammalian cells).10 Never-
theless, the effect of alkali-metal ions on acyl-group transfer
reactions has much less been investigated than that of multi-
valent metal ions.
Chart 1.
S
S
EtOM
MO
NO2
Ph P
O
NO2
Ph P OEt
OEt
OEt
5
EtOM : M = Li, Na, K, K/18C6
The first systematic study on the effect of alkali-metal ions
has been carried out by Buncel et al. for the nucleophilic
substitution reaction of 4-nitrophenyl diphenylphosphinate (1)
with alkali-metal ethoxides (EtOM; M = Li, Na, and K) in
anhydrous EtOH.3a They found that alkali metal ions catalyze
the reaction in the order K+ < Na+ < Li+, and the catalytic
effect disappears in the presence of complexing agents, e.g.,
18-crown-6-ether (18C6) for K+ ion or 2,1,1-cryptand for
Li+ ion.3 A similar result has been reported for the reaction of
4-nitrophenyl diethyl phosphate (3) with EtOM, i.e., M+ ions
catalyze the reaction and the catalytic effect increases in the
order K+ < Na+ < Li+.5
Interestingly, a contrasting result has been reported for the
corresponding reactions of O-4-nitrophenyl diphenylphos-
phinothioate (2) and O-4-nitrophenyl O,O-diethyl thiophos-
phate (4), i.e., the thio analogues of 1 and 3, respectively
(Chart 1).4,5 We have found that the reactions of 2 and 4 with
EtOM are inhibited by Li+ ion but are catalyzed by Na+ and
Scheme 1.
K+ ions, indicating that the M+ ion effects are dependent on the
nature of the electrophilic centers (e.g., P=O vs. P=S) as well
as on the size of alkali-metal ions.4,5
To get further information on the role of M+ ions, we have
extended our study to the reaction of O-ethyl O-4-nitrophenyl
phenylphosphonothioate (5), which is known as EPN and is
used as an insecticide just as paraoxon 3 and parathion 4,
with EtOM (M = Li+, Na+, and K+) in EtOH as shown in
Scheme 1. The kinetic data for the reaction of 5 in this study
have been compared with those reported previously for the
corresponding reactions of 2 and 4 to investigate the effect
of replacement of the Ph groups in the nonleaving group of
2 by one EtO (2 ¼ 5) or by two EtO groups (2 ¼ 4) on the
reactivity of the P=S centered electrophiles.
Published on the web March 27, 2013; doi:10.1246/bcsj.20130015

I.-H. Um et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 6 (2013)
737
our previous reports that the effect of M+ ions on reactivity is
strongly dependent on the nature of the electrophilic center.4,5
The downward curvature in the plot of kobsd vs. [EtOM] is
typical of reactions in which M+ ions were reported to behave
as an inhibitor.4,5 Thus, one can suggest that the reaction of
5 with EtOLi is also inhibited by Li+ ion. To examine Li+
ion behavior as an inhibitor in the current reaction, effects
of added LiSCN and KSCN on kobsd have been investigated
for the reactions of 5 with EtOLi and EtOK, i.e., at a given
concentration of EtOK (or EtOLi) with varying concentration
of LiSCN (or KSCN). The kinetic results are summarized in
Table 2 and are illustrated graphically in Figure 2.
One can see that the kobsd for the reaction of 5 with EtOK
decreases upon addition of LiSCN to the reaction mixture up to
[LiSCN]/[EtOK] µ 2 and then it remains nearly constant upon
further addition of LiSCN. On the contrary, the kobsd for the
reaction of 5 with EtOLi increases steeply as the concentration
of KSCN in the reaction mixture increases up to [KSCN]/
Results and Discussion
The kinetic study was carried out spectrophotometrically
under pseudo-first-order conditions in which the concentra-
tion of EtOM was in large excess over that of 5. The reaction
was monitored by measuring the absorbance of the leaving 4-
nitrophenoxide ion at 400 nm. All reactions in the current study
obeyed pseudo-first-order kinetics. Pseudo-first-order rate con-
stants (kobsd) were calculated from the slope of linear plots of
ln(A¨ ¹ At) vs. time. It is estimated from replicate runs that the
uncertainty in the kobsd values is less than «3%. The kinetic
results are summarized in Table 1 and are graphically illus-
trated in Figure 1. The second-order rate constants for the
¹
reactions of 5 with the dissociated EtO and ion-paired EtOM
ꢀ
(i.e., kEtO and kEtOM, respectively) were calculated from the
ion-pairing treatment of the kinetic data.
Effects of M+ Ions on Reactivity. As shown in Figure 1,
the reactivity of EtOM toward 5 is dependent on the size of
the alkali-metal ions, i.e., it increases in the order EtOLi <
EtONa < EtOK < EtOK/18C6. Besides, the plot of kobsd vs.
[EtOLi] curves slightly downward. This is in contrast to the
results reported previously for the corresponding reactions of
the P=O centered electrophiles 1 and 3 (e.g., EtOLi is more
reactive than EtONa or EtOK and the plot of kobsd vs. [EtOLi]
curves upward).3,5 The contrasting reactivities of EtOM toward
the P=O and P=S centered electrophiles are consistent with
Table 2. Summary of Kinetic Data for the Reactions of
5 with EtOLi/KSCN and EtOK/LiSCN in Anhydrous
EtOH at 25.0 « 0.1 °C, [5] = 4 © 10¹5 M and [EtOLi] =
[EtOK] = 6.05 © 10¹2 M
104kobsd
/s
104kobsd
/s
[KSCN]/[EtOLi]
[LiSCN]/[EtOK]
¹1
¹1
0
1.08
1.39
1.55
1.70
1.90
1.98
2.10
2.07
0
1.85
1.81
1.67
1.60
1.41
1.40
1.40
1.40
0.321
0.643
0.964
1.61
2.57
3.56
5.14
0.39
0.78
1.18
2.46
4.42
5.90
8.85
Table 1. Summary of Kinetic Data for the Reactions of 5
with EtOM in Anhydrous EtOH at 25.0 « 0.1 °C, [5] =
4 © 10¹5 M
¹1
EtOM
103[EtOM]/M
105kobsd/s
EtOLi
EtONa
EtOK
EtOK/18C6
21.0-83.8
20.4-96.0
21.2-90.1
19.6-71.9
4.02-14.3
5.61-27.4
6.54-28.9
6.42-27.1
0.0003
0.0004
EtOK/18C6
EtOK
EtONa
EtOLi
0.0002
0.0001
0.0000
0.0003
0.0002
0.0001
0.0000
0
3
6
9
0.00 0.02 0.04 0.06 0.08 0.10 0.12
[MSCN] / [EtOM]
[EtOM] / M
Figure 2. Plots showing the effects of added LiSCN and
KSCN on kobsd for reactions of 5 with EtOLi and EtOK
in anhydrous EtOH at 25.0 « 0.1 °C. [KSCN]/[EtOLi]
( ) and [LiSCN]/[EtOK] ( ). [5] = 4 © 10¹5 M and
[EtOK] = [EtOLi] = 6.05 © 10¹2 M.
Figure 1. Plots of kobsd vs. [EtOM] for the reactions of
5 with EtOLi ( ), EtONa ( ), EtOK ( ), and with EtOK in
the presence of 18C6 ( ) in anhydrous EtOH at 25.0 «
0.1 °C. [18C6]/[EtOK] = 2.0 and [5] = 4 © 10¹5 M.

738
Bull. Chem. Soc. Jpn. Vol. 86, No. 6 (2013)
Alkali-Metal Ion Catalysis and Inhibition
0.015
0.010
0.005
0.000
kEtO
EtOLi
EtONa
EtOK
5 + EtO + M+
Products
EtOK/18C6
Kd
kEtOM
5 + EtOM
Products
Scheme 2.
[EtOLi] µ 2 and then the increase in kobsd is insignificant
thereafter. Our preliminary experiment has shown that KSCN
and LiSCN are not reactive toward 5, indicating that SCN
ion does not behave as a nucleophile in this study. Thus, the
increase in the kobsd for the reaction with EtOLi upon addition
of KSCN is consistent with the fact that EtOK is more reactive
than EtOLi as shown in Figure 1. Furthermore, the decrease in
the kobsd for the reaction with EtOK upon addition of LiSCN
supports the premise that Li+ ion behaves as an inhibitor in the
¹
0.00 0.01 0.02 0.03 0.04 0.05
[EtO−]eq / M
¹
¹
Figure 3. Plots of kobsd/[EtO ]eq vs. [EtO ]eq for the reac-
tions of 5 with EtOLi ( ), EtONa ( ), EtOK ( ), and with
EtOK in the presence of 18C6 ( ) in anhydrous EtOH
at 25.0 « 0.1 °C. [18C6]/[EtOK] = 2.0.
reaction of 5.
À
Dissection of kobsd into kEtO and kEtOM
.
To quantify
the inhibitory or catalytic effect exerted by M+ ions, kobsd has
ꢀ
been dissected into kEtO and kEtOM, the second-order rate con-
stant for the reaction with the dissociated EtO and ion-paired
EtOM, respectively. It has previously been reported that EtOM
ꢀ
¹
Table 3. Summary of Second-Order Rate Constants (kEtO
and kEtOM) and the kEtOM/kEtO Ratios for the Reactions of
5 with EtOM in Anhydrous EtOH at 25.0 « 0.1 °C
ꢀ
¹
in anhydrous EtOH exists as dissociated EtO and ion-paired
EtOM when [EtOM] < 0.1 M.11 One might expect that weak
103kEtO
103kEtOM
/M¹1 s
kEtOM
/kEtO
ꢀ
ion-pairing of EtO to the 18C6-complexed K+ ion would
¹
EtOM
¹1
¹1
/M¹1 s
ꢀ
be also possible, since Lehn suggested that the crown-ether
complexed cation is accessible from above and below the plane
of the crown ether in the complexed M+ ion.12
EtOLi
EtONa
EtOK
EtOK/18C6
2.75 « 0.12
2.58 « 0.09
2.56 « 0.22
2.76 « 0.02
1.44 « 0.05
2.94 « 0.05
3.43 « 0.13
5.19 « 0.04
0.52
1.14
1.34
1.88
Since the concentration of EtOM used in this study is lower
¹
than 0.1 M, EtOM would exist as the dissociated EtO and
ion-paired EtOM. Thus, substrate 5 would react with both the
¹
dissociated EtO and ion-paired EtOM as shown in Scheme 2.
from the kEtOM/Kd ratios determined above and the Kd value
¹3
¹3
Equation 1 can be derived on the basis of the reactions
proposed in Scheme 2. Under pseudo-first-order kinetic con-
ditions, kobsd can be expressed as eq 2. Since the dissocia-
reported previously (i.e., Kd = 4.72 © 10 , 9.80 © 10 ,
11.1 © 10¹3, and 60.2 © 10¹3 M for EtOLi, EtONa, EtOK,
and EtOK/18C6, in turn).5a,13 The calculated kEtO and kEtOM
ꢀ
tion constant Kd = [EtO ]eq[M+]eq/[EtOM]eq, and [EtO ]eq
=
values in this way are summarized in Table 3 together with the
¹
¹
[M+]eq at equilibrium, eq 2 becomes eq 3. The concentrations
k
EtOM/kEtO ratios.
ꢀ
¹
of [EtO ]eq and [EtOM]eq can be calculated from the reported
Kd value and the initial concentration of EtOM (i.e., [EtOM]o)
using eqs 4 and 5.
As shown in Table 3, the second-order rate constant for the
¹
ꢀ
reaction with the dissociated EtO (i.e., kEtO ) is nearly
identical within the experimental error range regardless of
the nature of M+ ions. This is consistent with the fact that the
ꢀ
ꢀ
Rate ¼ kEtO ½EtO ꢁ ½5ꢁ þ kEtOM½EtOMꢁeq½5ꢁ
ð1Þ
ð2Þ
ð3Þ
ð4Þ
ð5Þ
kobsd ¼ kEtO ½EtO ꢁeeqq þ kEtOM½EtOMꢁ
¹
¹
plots of kobsd/[EtO ]eq vs. [EtO ]eq yield a common intercept
ꢀ
ꢀ
eq
ꢀ
(i.e., kEtO ) as shown in Figure 3. It is also noted that the
ꢀ
k
obsd=½EtOꢀꢁeq ¼ kEtO þ kEtOM½EtOꢀꢁeq=Kd
ꢀ
rate constant increases in the order kEtOLi < kEtO < kEtONa
k
<
½EtOMꢁo ¼ ½EtOꢀꢁeq þ ½EtOMꢁeq
¹
EtOK < kEtOK/18C6, indicating that the dissociated EtO is more
2
1=2
½EtOꢀꢁeq ¼ ½ꢀKd þ ðKd þ 4Kd½EtOMꢁoÞ ꢁ=2
reactive than the ion-paired EtOLi but is less reactive than the
other ion-paired species (e.g., EtONa, EtOK, and EtOK/18C6).
Thus, one can conclude that the current reaction is inhibited by
Li+ ion but is catalyzed by Na+, K+, and 18C6-complexed K+
ions although the catalytic effect is not significant. Interest-
ingly, the order of the reactivity of EtOM obtained in this study
is in contrast to that reported for the corresponding reactions of
¹
¹
One can expect that the plot of kobsd/[EtO ]eq vs. [EtO ]eq
would be linear with a positive intercept, if the reaction
proceeds as suggested in Scheme 2. In fact, the plots shown
in Figure 3 for the reaction of 5 with EtOM are linear with
a common intercept regardless of the size of M+ ions, indi-
cating that the above equations derived from the reactions in
ꢀ
Scheme 2 are indeed correct. Thus, one can calculate the kEtO
the P=O centered electrophiles 1 and 3 (i.e., kEtOLi > kEtONa >
3,5a
and kEtOM/Kd values from the intercept and the slope of the
linear plots, respectively. The kEtOM value can be calculated
k
EtOK > kEtO ).
The cause of the contrasting M+ ion effects
ꢀ
will be discussed in the following section.

I.-H. Um et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 6 (2013)
739
M
S
Sδ
EtO Pδ
Ph
O
O
Ph P O
Me
Mδ
O
δ
δ
δ
Me P O
Me
NO2
NO2
EtO P O
Ph
NO2
NO2
OEt
TS1
OEt
TS2
6
7
Chart 3.
Chart 2.
Role of M+ Ions and TS Structures. M+ ions would
catalyze the reaction of 5 with EtOM either by increasing
the electrophilicity of the reaction center through TS1 or by
enhancing the nucleofugality of the leaving group via TS2
(Chart 2). However, the enhanced nucleofugality through TS2
would be ineffective if the leaving group departure occurs after
the rate-determining step (RDS). The mechanism of the current
reaction has not been investigated. However, it is apparent
that the leaving group departure would occur after the RDS, if
the current reaction proceeds through a stepwise mechanism.
would interact strongly with Li+ ion but would exhibit a weak
interaction with 18C6-complexed K+ ion. This idea is con-
sistent with the kinetic results that the P=O/EtOLi and P=S/
EtOK-18C6 reactions are catalyzed whereas the P=S/EtOLi
reaction is inhibited as mentioned above.20
Factors Governing Reactivity: Steric Hindrance vs.
Electronic Effects. Steric hindrance has been suggested to
be an important factor that governs the reactivity of organo-
phosphorus compounds toward anionic nucleophiles such as
¹
¹ 6b,21,22
OH and EtO .
Cook et al.21 and Hawes et al.22 have
¹
This is because the incoming EtO is significantly more basic
found that the rate of alkaline hydrolysis of a variety of alkyl
phosphinates decreases significantly with increasing the steric
bulk of the alkyl substituent attached directly to the central P
atom. A similar result has recently been reported for alkaline
ethanolysis of 4-nitrophenyl diphenylphosphinate (1), 4-nitro-
phenyl methyl phenylphosphinate (6), and 4-nitrophenyl di-
methylphosphinate (7) (Chart 3).6b Buncel and his co-workers
have shown that the replacement of the Ph groups in 1 by one
Me group (1 ¼ 6) or by two Me groups (1 ¼ 7) causes a
systematic increase in reactivity of the series (i.e., 1 < 6 < 7).6b
Since it is evident that a Ph group would exert a stronger steric
hindrance than a Me group on the basis of the steric substituent
constant (i.e., Es = 0 and ¹2.55 for Me and Ph, respectively),23
the steric hindrance has been concluded to be an important
factor that determines the reactivity of the P=O centered
electrophiles 1, 6, and 7.6b
and a poorer nucleofuge than the leaving 4-nitrophenoxy ion.
Thus, TS2 cannot be responsible for the M+ ion catalysis if the
reaction proceeds through a stepwise mechanism. On the con-
trary, if the reaction proceeds through a concerted pathway, M+
ions would catalyze the reaction either through TS1 or via TS2.
We have recently reported that alkaline ethanolyses of
Y-substituted-phenyl diphenylphosphinates including 114 and
Y-substituted-phenyl diphenylphosphinothioates including 24
proceed through a concerted mechanism from various LFER
studies (e.g., Brønsted-type, Hammett and Yukawa-Tsuno
equations). Besides, alkaline hydrolysis of 1 and aminolysis
of 1, 2, and 3 have also been reported to proceed through a
concerted pathway.15-18 Accordingly, there is a high possibility
that the reaction of 5 with EtOM would proceed through a
concerted mechanism with a transition-state structure similar
to TS1 or TS2.
Table 3 shows that the second-order rate constant for the
If the catalytic effect of M+ ions originates from an increase
in the nucleofugality through complexation of M+ ions with
the O atom in the leaving 4-nitrophenoxide ion (i.e., TS2), one
might expect that the effect of M+ ions should be similar to that
reported for the corresponding reactions of the P=O centered
electrophiles (e.g., 1 and 3). This is because the leaving group
for these substrates is identical (i.e., 4-nitrophenoxide ion).
In fact, the effect of M+ ions for the current reaction of 5 is
analogous to that reported for the reactions of the P=S centered
electrophiles 2 and 4, but contrasts to that reported for the
corresponding reactions of the P=O centered electrophiles 1
and 3 (e.g., the reactivity of EtOM increases in the order
reaction of 5 with EtO (i.e., kEtO ) is ca. 2.65 © 10¹3 M¹1 s
,
¹
¹1
ꢀ
which is smaller than kEtO = 14.0 © 10¹3 M¹1 s for the
corresponding reaction of 24 but is much larger than kEtO
¹1
ꢀ
ꢀ
=
¹1
5.06 © 10¹5 M¹1 s for the reaction of 4.5a The reactivity of
these substrates would be influenced by the steric hindrance
and/or by the electronic effects of the Ph and EtO groups in
the nonleaving group of substrates 2, 4, and 5 (e.g., Ph2P=S,
(EtO)2P=S, and Ph(EtO)P=S for 2, 4, and 5, in turn). The Es
value for the EtO group is not available but it would be similar
to the Es value of ¹0.36 for the n-Pr group.23a It is apparent that
2 would experience a stronger steric hindrance than 4 and 5,
since -Es = ¹5.10 for the two Ph groups in 2, -Es = ¹2.91
for the Ph and EtO groups in 5 and -Es = ¹0.72 for the two
EtO groups in 4. Accordingly, 2 is expected to be less reac-
tive than 4 and 5, if the steric effect is an important factor to
affect their reactivity. However, as mentioned above, 2 is more
reactive than 4 and 5, indicating that the steric hindrance cannot
be responsible for the reactivity order found for these P=S
electrophiles. Interestingly, this is in contrast to the reports that
the steric hindrance is the most important factor that governs
the reactivity of the P=O centered electrophiles (e.g., 1, 6,
and 7).6b,21,22
¹
EtO < EtOK < EtONa < EtOLi for reactions of 1 and 3 but
¹
EtOLi < EtO < EtONa < EtOK for the reactions of 2 and
4).3-5 Therefore, the contrasting M+ ion effects found for the
reactions of the P=O and P=S centered electrophiles indicate
that the reaction proceeds through TS1 rather than TS2.
One might account for the contrasting M+ ion effects in
terms of the hard and soft acids and bases (HSAB) principle.19
According to the HSAB principle, the P=S centered electro-
phile 5 (a soft Lewis acid) would interact weakly with Li+
ion (a hard Lewis acid) but would exert a strong interaction
with the 18C6-complexed K+ ion (a soft Lewis acid). On the
contrary, the P=O electrophiles 1 and 3 (a hard Lewis acid)
Then, one might suggest that the reactivity of the P=S
centered electrophiles would be governed by electronic effects

740
Bull. Chem. Soc. Jpn. Vol. 86, No. 6 (2013)
Alkali-Metal Ion Catalysis and Inhibition
0
of 5 with EtOLi but curves upward for the corresponding
ꢀ
reaction with EtOK/18C6. (2) Dissection of kobsd into kEtO
and kEtOM has revealed that the reactivity increases in the
order EtOLi < EtO < EtONa < EtOK < EtOK/18C6, indi-
-1
¹
cating that the reaction is inhibited by Li+ ion but is catalyzed
by the other M+ ions in the order Na+ < K+ < K+/18C6. (3)
The reactions of 5 with EtOM proceed through TS1 rather than
via TS2. (4) The catalytic and inhibitory effects of M+ ions
are consistent with the HSAB principle, i.e., a poor inter-
action between Li+ (a hard Lewis acid) and the P=S centered
electrophile (a soft Lewis base) but a strong interaction
between 18C6-complexed K+ ion (a soft Lewis acid) and the
P=S electrophile. (5) The resonance effect of the Ph and EtO
groups in the nonleaving groups of the substrates is the most
important factor that governs the reactivity of the P=S centered
electrophiles 2, 4, and 5.
2
-2
5
-3
4
-4
-5
-6
-7
slope = 2.44 0.6
R2 = 0.971
Experimental
Materials. Substrate 5, KSCN, and LiSCN are commer-
cially available and were used without further purification. The
EtOM stock solutions were prepared by dissolving the respec-
tive alkali metal in anhydrous ethanol under N2 and were stored
in a refrigerator. The concentration of EtOM was measured
by titration with mono potassium phthalate. 18-Crown-6-ether
(18C6) was recrystallized from acetonitrile and dried under
vacuum. Anhydrous ethanol was further dried over magnesium
and distilled under N2 just before use.
-1.5
-1.0
-0.5
0.0
ΣσR
ꢀ
Figure 4. Plot of log kEtO vs. the -·R value of Ph and EtO
groups in the nonleaving group of substrates 2, 4, and 5.
-·R = ¹0.22 for Ph2 in 2, -·R = ¹0.72 for Ph and EtO
in 5, and -·R = ¹1.22 for (EtO)2 in 4.
(e.g., inductive and resonance effects) exerted by the Ph and
EtO groups in substrates 2, 4, and 5. Both Ph and EtO groups
would behave as an electron-withdrawing group (EWG)
through an inductive effect. The ·I value of Ph is 0.10.23a
Although the ·I value of EtO is not available, it would be
similar to that of MeO (·I = 0.27),23a indicating that EtO acts
as a stronger EWG than Ph through an inductive effect. Thus,
4 is expected to be more reactive than 2 or 5 if the inductive
effect is an important factor to determine the reactivity of the
P=S centered electrophiles. However, as mentioned above, 4 is
less reactive than 2 and 5, indicating that the inductive effect
is not responsible for the reactivity order found for the P=S
centered electrophiles.
Kinetics. Kinetic study was performed using a UV-vis
spectrophotometer equipped with a constant-temperature cir-
culating bath. The reactions were followed by monitoring the
appearance of the leaving 4-nitrophenoxide at 400 nm. Reac-
tions were followed generally for 9 half-lives and kobsd were
calculated using the equation, ln(A¨ ¹ At) vs. t. All solutions
were prepared just before use under nitrogen and transferred
by using gas-tight syringes. Typically, the reaction was initiated
by adding 0.02 M solution of substrate 5 in MeCN (5 ¯L)
using a 10 ¯L syringe to a 10 mm quartz UV cell containing the
thermostated reaction mixture made up of anhydrous EtOH and
aliquot of the EtOM solution.
Both Ph and EtO groups would act also as an electron-
donating group (EDG) through resonance interactions. How-
ever, the latter is expected to be a stronger EDG than the former
on the basis of the Taft’s ·R values (e.g., ·R = ¹0.11 and
¹0.61 for Ph and EtO, respectively).23b This idea accounts for
the fact that the reactivity increases in the order 4 < 5 < 2.
Thus, one can conclude that the resonance effect is the most
important factor that governs the reactivity of 2, 4, and 5. To
This research was supported by Basic Science Research
Program through the National Research Foundation of Korea
(NRF) funded by the Ministry of Education, Science and
Technology (KRF-2012-R1A1B3-001637). J. S. Kang is also
grateful for the BK 21 Scholarship.
References
1
a) M. F. Mohamed, I. Sánchez-Lombardo, A. A. Neverov,
ꢀ
support this idea, a plot of log kEtO vs. -·R has been con-
R. S. Brown, Org. Biomol. Chem. 2012, 10, 631. b) I. F. Barrera,
C. I. Maxwell, A. A. Neverov, R. S. Brown, J. Org. Chem.
2012, 77, 4156. c) M. A. R. Raycroft, C. T. Liu, R. S. Brown,
Inorg. Chem. 2012, 51, 3846. d) R. S. Brown, in Progress in
Inorganic Chemistry, ed. by K. D. Karlin, John Wiley & Sons,
Inc., Hoboken, NJ, USA, 2012, Vol. 57, p. 55. doi:10.1002/
9781118148235.ch2. e) B. B. Dhar, D. R. Edwards, R. S. Brown,
Inorg. Chem. 2011, 50, 3071.
structed for the reactions of 2, 4, and 5. As shown in Figure 4,
the plot is linear with a slope of 2.44 although the correlation
coefficient is not excellent. Such a large slope supports the
idea that the resonance effect is the most important factor
that controls the reactivity of the P=S centered electrophiles
2, 4, and 5.
Conclusion
2
a) W. Chei, H. Ju, J. Suh, Bioorg. Med. Chem. Lett. 2012,
The current study has led us to conclude the following: (1)
The plot of kobsd vs. [EtOM] curves downward for the reactions
22, 1533. b) W. S. Chei, H. Ju, J. Suh, JBIC, J. Biol. Inorg. Chem.
2011, 16, 511. c) H. M. Kim, B. Jang, Y. E. Cheon, M. P. Suh, J.

I.-H. Um et al.
Bull. Chem. Soc. Jpn. Vol. 86, No. 6 (2013)
Bull. Korean Chem. Soc. 2011, 32, 1951.
10 a) D. W. Martin, P. A. Mayes, V. W. Rodwell, D. K.
Granner, Harper’s Review of Biochemistry, 20th ed., Lange
Medical Publications, Los Altos, 1985, p. 630. b) H. Dugas,
Bioorganic Chemistry, 2nd ed., Springer-Verlag, New York, 1989,
p. 284.
11 V. Pechanec, O. Kocián, J. Závada, Collect. Czech. Chem.
Commun. 1982, 47, 3405.
12 J. M. Lehn, Pure Appl. Chem. 1980, 52, 2303.
13 J. Barthel, J.-C. Justice, R. Wachter, Z. Phys. Chem. 1973,
84, 100.
741
Suh, JBIC, J. Biol. Inorg. Chem. 2009, 14, 151. d) G. Feng, E. A.
Tanifum, H. Adams, A. C. Hengge, N. H. Williams, J. Am. Chem.
Soc. 2009, 131, 12771. e) T. Humphry, S. Iyer, O. Iranzo, J. R.
Morrow, J. P. Richard, P. Paneth, A. C. Hengge, J. Am. Chem. Soc.
2008, 130, 17858. f) J. H. Lee, J. Park, M. S. Lah, J. Chin, J.-I.
Hong, Org. Lett. 2007, 9, 3729. g) M. Livieri, F. Mancin, G.
Saielli, J. Chin, U. Tonellato, Chem.®Eur. J. 2007, 13, 2246.
h) T. H. Fife, M. P. Pujari, Bioorg. Chem. 2000, 28, 357. i) T. H.
Fife, R. Bembi, J. Am. Chem. Soc. 1993, 115, 11358.
3
a) E. Buncel, E. J. Dunn, R. A. B. Bannard, J. G. Purdon,
J. Chem. Soc., Chem. Commun. 1984, 162. b) E. J. Dunn, E.
Buncel, Can. J. Chem. 1989, 67, 1440. c) M. J. Pregel, E. J. Dunn,
R. Nagelkerke, G. R. J. Thatcher, E. Buncel, Chem. Soc. Rev. 1995,
24, 449.
14 I.-H. Um, J. E. Park, Y.-H. Shin, Org. Biomol. Chem. 2007,
5, 3539.
15 I.-H. Um, J.-Y. Han, S.-J. Hwang, Chem.®Eur. J. 2008, 14,
4
I.-H. Um, Y.-H. Shin, J.-E. Park, J.-S. Kang, E. Buncel,
7324.
Chem.®Eur. J. 2012, 18, 961.
16 a) I.-H. Um, J.-Y. Han, Y.-H. Shin, J. Org. Chem. 2009, 74,
3073. b) I.-H. Um, Y.-H. Shin, J.-Y. Han, M. Mishima, J. Org.
Chem. 2006, 71, 7715.
17 I.-H. Um, K. Akhtar, Y.-H. Shin, J.-Y. Han, J. Org. Chem.
2007, 72, 3823.
5
a) I.-H. Um, Y.-H. Shin, S.-E. Lee, K. Yang, E. Buncel,
J. Org. Chem. 2008, 73, 923. b) I.-H. Um, S.-E. Jeon, M.-H. Baek,
H.-R. Park, Chem. Commun. 2003, 3016.
6
a) I. S. Koo, D. Ali, K. Yang, Y. Park, A. Esbata, G. W.
van Loon, E. Buncel, Can. J. Chem. 2009, 87, 433. b) I. Onyido,
K. Albright, E. Buncel, Org. Biomol. Chem. 2005, 3, 1468. c) E.
Buncel, K. G. Albright, I. Onyido, Org. Biomol. Chem. 2004,
2, 601.
18 A.-R. Bae, J. Lee, I.-H. Um, Bull. Korean Chem. Soc. 2013,
34, 201.
19 a) R. G. Pearson, J. Songstad, J. Am. Chem. Soc. 1967, 89,
1827. b) T. L. Ho, in Hard and Soft Acid and Bases, ed. by R. G.
Pearson, Academic Press, New York, 1977.
7
a) R. Cacciapaglia, L. Mandolini, A. Tomei, J. Chem. Soc.,
¹
Perkin Trans. 2 1994, 367. b) R. Cacciapaglia, L. Mandolini,
Chem. Soc. Rev. 1993, 22, 221. c) R. Cacciapaglia, A. R.
Van Doorn, L. Mandolini, D. N. Reinhoudt, W. Verboom, J. Am.
Chem. Soc. 1992, 114, 2611.
20 A reviewer suggested that “Li+ binds strongly with EtO ,
and this, together with the absence of a strong catalytic effect,
results in the decreased reactivity of EtOLi compared to the free
¹
EtO .”
8
M. J. Pregel, E. J. Dunn, E. Buncel, J. Am. Chem. Soc.
21 a) R. D. Cook, C. E. Diebert, W. Schwarz, P. C. Turley, P.
Haake, J. Am. Chem. Soc. 1973, 95, 8088. b) R. D. Cook, S. Farah,
L. Ghawi, A. Itani, J. Rahil, Can. J. Chem. 1986, 64, 1630.
22 W. Hawes, S. Trippett, Chem. Commun. 1968, 577.
23 a) T. H. Lowry, K. S. Richardson, Mechanism and Theory
in Organic Chemistry, 3rd Ed., Harper/Collins, New York, 1987,
pp. 153-157. b) S. Ehrenson, R. T. C. Brownlee, R. W. Taft, Prog.
Phys. Org. Chem. 1973, 10, 1.
1991, 113, 3545.
9
a) I.-H. Um, J.-S. Kang, Y.-H. Shin, E. Buncel, J. Org.
Chem. 2013, 78, 490. b) I.-H. Um, J.-Y. Seo, J.-S. Kang, J.-S. An,
Bull. Chem. Soc. Jpn. 2012, 85, 1007. c) I.-H. Um, J.-S. Kang,
C.-W. Kim, J.-I. Lee, Bull. Korean Chem. Soc. 2012, 33, 519.
d) J.-S. An, G. NamKoong, J.-S. Kang, I.-H. Um, Bull. Korean
Chem. Soc. 2011, 32, 2423. e) S.-Y. Choi, Y.-J. Hong, I.-H. Um,