The mechanisms of hydrolysis of N-alkyl O-arylthioncarbamate esters

Article abstract of DOI:10.1002/poc.1722

The hydrolysis of N-ethyl O-p-methoxyphenylthioncarbamate (EMeOT) at 50°-C was studied in the range of H^X_o S3.6 to HS 13.7. The pH-rate profile showed that the hydrolysis occurred through specific acid catalysis at pH <2, spontaneous hydrolysis at pH 2-3, and specific basic catalysis at pH >3. The excess acidity plot against X was linear with slope 0.93, and the Bunnett-Olsen coefficient was 0.07. The acid hydrolysis occurred by an A1 mechanism. The basic hydrolysis of EMeOT can be explained if the mechanism is E1cb. At pH >3 the rate constants increased, reaching a constant value indicating that the expulsion of the aryloxy is not concerted. The neutral species hydrolyzed with general base catalysis with Bronsted β=.63±0.07. Water acted as a general base catalyst with (pseudo-) first-order rate constant k_N=(2.6±0.2)×10^-8 s^-1, and inverse kinetic solvent isotope effect of k^D _o =k^H_o= 2:76 consistent with a transfer of the proton at a late transition state, as also supported by the highly negative entropy of activation (-31 cal K^-1 mol^-1). The polynomial expression of the proton inventory curve presented a minimum of the standard deviations that favors the assumption that there are three active protons. The N to O proton transfer to the water molecule forms an incipient hydron. The fractionation factor of the TS of the protons indicated that the hydron is ca. 68% developed at the transition state. Copyright

Full text of DOI:10.1002/poc.1722

Research Article
Received: 1 February 2010,
Revised: 13 March 2010,
Accepted: 30 March 2010,
Published online in Wiley Online Library: 29 June 2010
(
wileyonlinelibrary.com) DOI 10.1002/poc.1722
The mechanisms of hydrolysis of N-alkyl
O-arylthioncarbamate esters
y
a
a
a
Eduardo Humeres *, Eduardo P. de Souza and Nito A. Debacher
X
o
The hydrolysis of N-ethyl O-p-methoxyphenylthioncarbamate (EMeOT) at 50 -C was studied in the range of H S3.6 to
S
H 13.7. The pH-rate profile showed that the hydrolysis occurred through specific acid catalysis at pH <2,
spontaneous hydrolysis at pH 2–3, and specific basic catalysis at pH >3. The excess acidity plot against X was linear
with slope 0.93, and the Bunnett–Olsen coefficient was 0.07. The acid hydrolysis occurred by an A1 mechanism. The
basic hydrolysis of EMeOT can be explained if the mechanism is E1cb. At pH >3 the rate constants increased, reaching a
constant value indicating that the expulsion of the aryloxy is not concerted. The neutral species hydrolyzed with
general base catalysis with Brønsted b ¼0.63 W 0.07. Water acted as a general base catalyst with (pseudo-) first-order
S8 S1
D
H
rate constant k ¼(2.6 W 0.2) T 10
s
, and inverse kinetic solvent isotope effect of k =k ¼2:76 consistent with a
N
o
o
transfer of the proton at a late transition state, as also supported by the highly negative entropy of activation
S31 cal K mol ). The polynomial expression of the proton inventory curve presented a minimum of the standard
S1
S1
(
deviations that favors the assumption that there are three active protons. The N to O proton transfer to the water
molecule forms an incipient hydron. The fractionation factor of the TS of the protons indicated that the hydron is ca.
68% developed at the transition state. Copyright ß 2010 John Wiley & Sons, Ltd.
Keywords: general base catalysis; hydrolytic mechanisms; N-ethyl O-p-methoxyphenylthioncarbamate; proton inventory
catalysis and in the spontaneous hydrolysis water acted as a
INTRODUCTION
general base catalyst. The water-catalyzed reaction should be at
least bimolecular but the exact value could not be determined
from simple kinetic data. In the absence of other general bases,
the pH independent hydrolysis is the only reaction. The slow
proton transfer from the thion ester is the consequence
of the low acidity of the N—H group. The Brønsted plot
suggested that the transition state is highly polar resulting in the
The reaction of carbon disulfide with alkoxides, halides, and
[
1–4]
amines produces thioncarbamate esters 1 (Eqn 1)
that are
intensely used as collectors for the flotation of a variety of
[
5–10]
[11–14]
metals,
as well as pesticides,
chemotherapeutic and
[
15,16]
[17]
metastatic agents,
industrial applications.
enzyme immobilization, and in many
18,19]
[
[
20]
observed high negative entropy of activation.
For the alkyl
N-arylthioncarbamates esters, the dissociation of the N—H group
is several pK units more favorable and did not present general
[
21]
base catalysis.
A description of the cybotactic region of hydration of
carbohydrates has been obtained by comparing the reactivities
of polysaccharide derivatives to small molecules with the same
ð1Þ
Because of the wide industrial applications of thioncarbamates,
the study of their reactivity in aqueous media is very important
because the thioncarbamate is a highly stable group. Their
[
22]
functionalities. The water catalyzed reaction of cellulose
and
[
23]
amylose xanthate esters was about three orders of magnitude
faster than that of the analogous small molecule, and it was
proposed that the acceleration is a consequence of the strong 3D
hydrogen-bonded network of water of the solvation shell
induced by the polysaccharide. MD simulations of a model of
—
biological activity depends on the C—S group which can stabilize
carbanions. The thiocarbonyl group is a powerful electron-
withdrawing group because sulfur can easily accept electrons.
There is a duality of mechanisms for the basic hydrolysis
of thioncarbamate esters depending on the availability of
a proton on the nitrogen atom of the ester. For alkyl
N-alkylthioncarbamate esters mechanism BAc2 applies if there
is no proton on the nitrogen (N,N-disubstituted nitrogen), but if
the nitrogen contains a proton, the reaction occurs through the
*
Correspondence to: E. Humeres, Departamento de Qu ´ı mica, Universidade
Federal de Santa Catarina, 88040-900 Florian o´ polis, SC, Brazil.
E-mail: humeres@mbox1.ufsc.br
[7]
E1cb mechanism. The E1cb mechanism involves the elimin-
ation of an alkyloxide ion from the thioncarbamate anion,
producing an isothiocyanate intermediate that decomposed
rapidly to form alkylamine and COS. The pH rate profile of alkyl
N-alkylthioncarbamate esters also showed that the hydrolysis
occurred through specific acid catalysis at pH <2 by an A1
mechanism. The neutral species hydrolyzed with general base
a
E. Humeres, E. P. de Souza, N. A. Debacher
Departamento de Qu ´ı mica, Universidade Federal de Santa Catarina,
88040-900 Florian o´ polis, SC, Brazil
y
This article is published in Journal of Physical Organic Chemistry as a special
issue on Tenth Latin American Conference on Physical Organic Chemistry,
edited by Faruk Nome, Dept de Quimica, Universidade Federal de Santa
Catarina, Campus Universitario – Trindade 88040-900, Florianopolis-SC, Brazil.
J. Phys. Org. Chem. 2010, 23 915–924
Copyright ß 2010 John Wiley & Sons, Ltd.

E. HUMERES, E. P. DE SOUZA AND N. A. DEBACHER
9
8
7
6
5
4
3
2
1
0
cellulose solvated in water showed a well-structured first
solvation shell indicating that it had a stronger H-bond structure
of water around due to the cooperative effect of the neighboring
[
24]
residues.
In this work we have studied the mechanisms of
hydrolysis of N-alkyl O-arylthioncarbamate esters, in particular,
the water catalyzed hydrolysis. The release of the aryloxide
chromophore is easier than the alkoxide and will allow us in a
future study to compare the heterogenous water reaction when
the thioncarbamate moiety is bound to a carbohydrate-like
quitosan that contains an amino group.
RESULTS AND DISCUSSION
-
4
-2
0
2
4
6
8
10
12
14
N-alkyl O-arylthionocarbamates can be prepared from
O-arylchlorothioformate obtained from the reaction of the
corresponding phenol and thiophosgene followed by aminoly-
x
Ho
pH
Figure 1. pH-rate profile of the hydrolysis of EMeOT at 50 8C; *, unbuf-
fered; &, values extrapolated to zero buffer concentration; D, in 0.01 M
sulfuric acid. The line was drawn according to Eqn (3) with the following
[
25,26]
sis,
or by the addition of the phenol to an alkylisothiocya-
[
25]
nate. O-arylthionocarbamate esters hydrolyze in basic medium,
therefore the basicity must be controlled during the synthesis. The
synthesis of N-ethyl O-p-methoxyphenylthioncarbamate, EMeOT,
was performed in a mixture of CH Cl /H O and the pH was
ꢀ5
ꢀ1 ꢀ1
ꢀ8 ꢀ1
values:
k
H
¼4.0 ꢂ10
M
s
;
pK
1
¼ꢀ2.3;
k
N
¼2.60 ꢂ10
s ;
ꢀ
2
ꢀ1
50
w
k ¼28.9 ꢂ10
E
s
NH
; pK ¼10.5; pK ¼13.26. All the constants were
experimentally obtained; pKNH was calculated from the profile; k and K
H
1
2
2
2
[
27]
controlled by a pH 7 phosphate buffer (Eqn 2).
were optimized considering the value of log kH=K1 ¼ꢀ6.8 obtained from
the excess acidity plot
The profile can be kinetically described by Eqn (3), which assumes
that the basic hydrolysis occurs by the E1cb mechanism as will be
discussed below.
ꢀ
aH
þ
kN kEK2½OH ꢁ
o
obs
k
¼kH
0þK0þ
(3)
0
K
K1K
a
þ
2
K K
w
0
H
where K ¼
þ1 þa and aH
þ
¼ho when pH < 2
K1
þ
H
Equation (3) can be approximated to Eqn (4)
kHho
kEKNH
o
obs
k
¼
þkN þ
aH
(4)
ho þK1
þ
þKNH
ð2Þ
where K
(
K
2 w
¼KNH, is the acid dissociation constant of EMeOT
from the pH-rate profile, pKNH ¼10.5)
Acid hydrolysis
pH-rate profile of EMeOT
When the acid concentration is higher than 1 M, Eqn (4) becomes
Eqn (5)
The pH-rate profile of the hydrolysis of EMeOT at 50 8C in the
X
range of H ꢀ3.6 to H
obs
-
13.7 is shown in Fig. 1. The values of the
were obtained in the absence of buffer or
o
o
rate constants k
H o
k h
o
obs
extrapolated to zero buffer concentration when general catalysis
k
¼
(5)
ho þK1
X
was observed. The values of H and H were corrected to
o
-
ꢀ
[
28,29]
aHþ
kN
kEK2½OH
ꢁ
50 8C.
because kH K1K
0
>> K
0
þ
0
KwK
þ
ꢀ
X
o
X
o
In Scheme 1 the reactive species are SH , SH and S , K
1
and K
2
and ho ¼anti log H , where for HCl H ¼ꢀðX þlog C
þ
H
Þ,
2
are the acid dissociation and reverse base dissociation equi-
X ¼excess acidity.
þ
librium constants of species SH2 and SH, respectively; k
H
is the
The pH-rate profile in the range of 1–10 M HCl suggests that
the substrate becomes partially protonated. For the A1
mechanism, fast pre-equilibrium protonation followed by
specific acid hydrolysis rate constant; k
N
and k
E
are the rate
constants of spontaneous and basic hydrolysis, respectively.
Scheme 1. Kinetic scheme of the hydrolysis of EMeOT
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Copyright ß 2010 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2010, 23 915–924

HYDROLYSIS OF N-ALKYL O-ARYLTHIONCARBAMATE ESTERS
unimolecular rate-determining reaction of the protonated
[
28]
substrate, the rate equation is
ꢀ
ꢁ
fSH
þ
o
obs
2
k
CSH2
þ
þCSH ¼koCSH2
þ
(6)
f
6¼
1
Substituting CSH2þin terms of K and making the excess acidity
[
29–32]
assumption for the ratio of the activity coefficients,
and (8) are obtained
Eqns (7)
CSH
ko
6
ꢃ
log kobs ꢀlog
ꢀlog CH
þ
¼log þm m X
K1
(7)
(8)
CSH
þ
þCSH
K1
2
ko
6
ꢃ
log kobs ꢀlog
ꢀlog CH
þ
¼log þm m X
K1 þho
K1
where CSH2þ and CSH are the concentrations of the proto-
nated and unprotonated substrates, respectively, ko is the
medium-independent specific acid catalysis rate constant, and
CSH
K
1
ꢄ
K1þho
C
þþCSH
SH
2
K1
K1þho
The plot of (log kobs ꢀlog
ꢀlog CH
þ
) versus X was linear
6¼
ꢃ
ko
K1
with slope m m ¼0:93 ꢅ0:08 and intercept log ¼ꢀ6:83 ꢅ
0
:13 (Fig. 2). These plots are curved for A2 mechanism and are
6
[29–31]
always linear with m > 1 for A1 mechanism.
acidity slope values m have been associated with solvation
differences between SH and SH .
The excess
*
þ
[33]
2
6¼
For HCl, the excess acidity slope m mꢃis related to the
Scheme 2. A1 mechanism of the acid hydrolysis of EMeOT
6
Bunnett–Olsen coefficient f
ꢀf , and therefore, f ¼0.07.
6
by the relationship m mꢃ¼
[
20]
1
The Bunnett–Olsen coeffi-
Basic hydrolysis
6¼
6¼
cient near zero indicates that the hydration of SH and the
At pH >4, the pH rate profile of EMeOT presents an increase of
þ
[34]
conjugate acid SH2 are practically the same,
and since the
the rate constants that reached a plateau at high basicity. At pH
structure of the conjugate acid should be close to the TS, this
result is also consistent with an A1 mechanism.
>
4 Eqn (3) and (4) become Eqn (9).
According to this mechanism, the conjugate acid of the
thioncarbamate is N-protonated producing in the rate-
determining step ethylamine and p-methoxyphenyl thionformyl
cation which upon fast hydrolysis produces COS and
p-methoxyphenol (Scheme 2).
ꢀ
kEK2½OH ꢁ
kEKNH
o
obs
k
¼
¼
(9)
ꢀ
1
þK2½OH ꢁ aH
þ
þKNH
ꢀ
a
k K2½OH
E
ꢁ
þ
k
K
H
N
because 1
ꢀ
>> kH
0
þ
0
þK2½OH
ꢁ
K1K
Equation (9) assumes that the specific base catalysis occurs
through the E1cb mechanism. Basic hydrolysis of EMeOT at 25 8C
in the range of 0.7–2.9 M NaOH gave a constant value of the
The more stable form of the intermediate is protonated on
sulfur but the N-protonated intermediate is the reactive tautomer
in equilibrium that decomposes via A1 mechanism. The
alternative O-protonation of the aryloxy was not considered
because it leads to the formation of ethylisothiocyanate that is
stable under acid conditions and it was not observed as a
ꢀ3
ꢀ1
first-order elimination rate constant k ¼(20.2 ꢅ0.2) ꢂ10
s
E
ꢀ2
ꢀ1
s
or (28.9 ꢅ0.3) ꢂ10
at 50 8C (from Eyring equation)
according to the E1cb mechanism. If the reaction would occur
o
obs
[
21]
by a B 2 mechanism (Scheme 3), k would be given by Eqn
product.
Ac
KNH
ꢀ1 ꢀ1
[35]
(
10), and k2 ¼KW kE ¼167.24 M
s
(pK ¼13.262 at 50 8C).
W
-
-
-
-
-
4,5
5,0
5,5
6,0
6,5
k2Kw
kobs ¼
(10)
aH
þ
þKNH
The elimination rate constant k
E
measures the rate of
elimination of the p-methoxyphenyloxy anion from the thion-
carbamate anion (Scheme 3) producing an ethylisothiocyanate
intermediate that decomposes rapidly to form ethylamine and
COS as products. The BAc2 mechanism produces a tetrahedral
intermediate, in the slow step with the second-order rate k2,
which forms the products through several consecutive fast
reactions. Neither of these mechanisms can be distinguished
kinetically, as shown by Eqns (9) and (10). Both mechanisms have
0,5
1,0
1,5
2,0
2,5
X
[20,36,37]
been observed for carbamate and thioncarbamate esters.
Figure 2. Excess acidity plot of the hydrolysis of EMeOT in HCl at 50 8C;
It has been observed that hydrolyses of carbamate esters
occurring through the E1cb mechanism are faster than those
ko
slope 0.93ꢅ0.08, intercept log ¼ꢀ6.83 ꢅ0.13, r ¼0.987
K1
J. Phys. Org. Chem. 2010, 23 915–924
Copyright ß 2010 John Wiley & Sons, Ltd.
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E. HUMERES, E. P. DE SOUZA AND N. A. DEBACHER
Table 2. General catalysis of the hydrolysis of EMeOT at
5
0.0 8C
pK 5a 0
a
kB (M
ꢀ1 ꢀ1
s )
Conjugate base
10 b
H2O
ꢀ1.74
2.85
4.79
4.74 ꢂ10ꢀ
ꢀ6
Chloroacetate
Acetate
Imidazol
5.83 ꢂ10
ꢀ7
9.91 ꢂ10
c
ꢀ4
6.46
2.02 ꢂ10
a
b
c
[19]
Reference
.
Considering water molarity 54.83 at 50 8C.
Reference
[51]
.
Scheme 3. Mechanisms involved in the basic hydrolysis of EMeOT at
0 8C
5
[
46]
occurring through the B 2 mechanism because of the decrease
Ac
group < 10–11). Considering the pKa of ethanol (16)
and
6¼ [20,36–39]
[46]
of DH .
When the reaction occurs by the E1cb mechanism, the
isothiocyanate intermediate can be trapped in the presence of
p-methoxyphenol (10.4) it is apparent that when substituting
ethyloxy for p-methoxyphenyloxy the nucleofugality of this
moiety is larger than ethylthioxy. Consequently, the difference
[
20,21]
6
ꢀ1
excess of an alkylamine with formation of a dialkyl thiourea.
DDG ¼5.7 kcal mol between ETE and EMeOT can only be
However, this reaction cannot be used for EMeOT because the
substrate itself reacts with the amine to form the corresponding
thiourea by preferential expulsion of the p-methoxyphenyloxy
anion because the NHR group presents the poorest intrinsic
explained if the mechanism of basic hydrolysis is E1cb.
E
Additionally, the constant value of k after the N—H dissociation
indicates that the expulsion of the aryloxide is not concerted and
proceeds in a second step. The small negative entropy of
[
27,40]
ꢀ1 ꢀ1
nucleofugality index.
activation (ꢀ8 cal mol
K ) is within the range reported for this
[
47,48]
The activation parameters of the specific base catalyzed
hydrolysis of EMeOT were measured at 1.50 M NaOH, in the range
of 35–50 8C, in the region where the NH bond is completely
ionized (Table 1). We found that the basic hydrolysis of N-ethyl
unimolecular mechanism.
General catalysis
[
7]
General base catalysis was observed for the hydrolysis of EMeOT
O-ethylthioncarbamate (ETE) occurs by the E1cb mechanism.
6¼
for pH ꢆ2 for general bases with pK in the range of ꢀ1.74 to 6.5
a
Comparison of DG of ETE and EMeOT shows that the rate
determining step of EMeOT is 5.7 kcal mol more favorable than
ꢀ1
and for general base second-order rate constants in a range of
6
1
0 order of magnitude (Table 2). The Brønsted plot was linear
ETE. The rate-determining step of the B 2 mechanism is the
Ac
with b ¼0.63 ꢅ0.07, r ¼0.936 (Fig. 3). At constant hydroxide ion
concentration the basic component of buffers linearly increased
the observed rate constants. The N—H bond is the only
dissociable bond in EMeOT. Similar results were obtained for ethyl
N-ethylthioncarbamate at 100 8C, where the general base
second-order rate constants of the dianions were all larger than
nucleophilic attack of the hydroxide ion on carbon of the
thiocarbonil group which would be favored by a decrease of
the electronic density. However, substitution of ethyl for
p-methoxyphenyl increases the electronic density and the basic
hydrolysis of EMeOT should be slower, not faster, than ETE.
In the case of the E1cb mechanism, the r.d.s. is the expulsion of
the aryloxy moiety from the thioncarbamate anion. For the same
mechanism, the nucleofugality of a group depends on the
substrate and solvent. In aqueous solution, the thioncarbamate
anion of Scheme 3 expels the p-methoxyphenyloxy anion by a
unimolecular mechanism, and in this case the nucleofugality
[
20]
the monoanions. No general base catalysis has been observed
[
21,47]
for carbamate or thioncarbamate esters
except a weak
[
48]
catalysis for N-methyl O-p-nitrophenylcarbamate.
K2
ꢀ
ꢀ
SH þ OH ÐS þH2O
(11)
[
40]
would depend only on the substrate.
For the same reaction,
the nucleofugality and the pKa of the conjugate acid of the
The deprotonation step by hydroxide ion is thermodynamically
[
41–43]
nucleofuges are well correlated.
Basic hydrolysis of
favorable (pK ¼ꢀ4.5 in equilibrium 11, refer Scheme 1) but the
2
carboxylate esters with fairly acidic a-protons, such as aryl
second-order rate constant k should not necessarily be near
OH
[
44]
[45]
1
acetoacetate
and fluorene-9-carboxylate
esters, has been
diffusion control. The H NMR spectrum of EMeOT (refer the
found to undergo a change in mechanism from BAc2 to E1cb with
Experimental Section) showed that about 70% of the compound
better nucleofuges (pK
a
value of the conjugate acid of the leaving
was in the cis-conformation due to the extended delocalization of
a
Table 1. Activation parameters for the hydrolysis of EMeOT
6
ꢀ1
6
ꢀ1
6
ꢀ1 ꢀ1
Hydrolysis
DG (kcal mol
)
DH (kcal mol
)
DS (cal mol K )
Water catalysis
Basic
pH 2
NaOH, 1.5 M
30.2 ꢅ2.2
19.9 ꢅ2.0
20.1 ꢅ1.0
17.3 ꢅ1.0
ꢀ31.2 ꢅ3.1
ꢀ8 ꢅ3
a
Standard state: 1 M, 50 8C.
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Copyright ß 2010 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2010, 23 915–924

HYDROLYSIS OF N-ALKYL O-ARYLTHIONCARBAMATE ESTERS
8
ArylO
C
N
H
-
OH
Ac
Im
Im
6
ClAc
H2O
ClAc
19.8
4
-
OH 13.1-11.6
Ac
6
.7
2
S-
0
H O
2
2
4.4
6.0
8.4
Im
Ac
2
7.9
-
2
0
2
4
6
8
pKa
26.7
11.3
ClAc
Figure 3. Brønsted plot of the general base catalysis of the hydrolysis of
EMeOT at 50.0 8C; b ¼0.63 ꢅ0.07; r ¼0.936
3
2.8
18.1
H2O
B
+ SH
the p-electrons that produces a partial double C—N bond. After
ionization there is an increase of the delocalization in the C(S)-N
moiety that produces a low value of the proton transfers involved
in equilibrium 11. When the acid and its conjugate base differ in
their electron distribution and molecular structure, i.e. the proton
transfer is associated with a resonance or tautomeric transform-
Figure 4. Free energy profile of the general base catalyzed hydrolysis of
EMeOT at 50.0 8C. The numbers on the left, for each base, are the values of
6
the N-deprotonation energy barrier DG of the SH þB reaction. The
SH
ꢀ
o
numberKs2 below
S
correspond to DG for the equilibrium
ꢀ
SH þB !S þBH (without considering the charges on B and BH). For
SH
[
49]
ꢀ
6
ꢀ1
5
ation, the reaction rates may be relatively low. For example, for
OH the values of DG ¼13.1 and 11.6 kcal mol correspond to the
4
ꢀ1 ꢀ1
s , respectively
2
,4-dihydroxy-4’-nitroazobenzene (DpK ꢀ3.9), acetylacetone
CO
are 4.75 ꢂ10 , 4 ꢂ10 , and 1 ꢂ10 M
dotted lines below N. . .H assuming kOH ¼10 –10 M
(
DpK ꢀ6.8), and H
2
3
(DpK ꢀ9.4), the values of the rate
5 4 4 ꢀ1 ꢀ1
P
constants k
s
,
becomes kobs
¼
k ½Bꢁwhere the term due to the specific base
OH
B
4
5
ꢀ1 ꢀ1
respectively. If kOH for EMeOT were 10 –10 M s
, considering
kꢀH Oshould be
and also kꢀH O ꢄk : the
hydrolysis should be added. Then the total rate constant
observed in the presence of an external buffer at pH > 2 is
H2O
4
k
OH
kꢀH2
that
.3–3.0 M
ionization is in the borderline of the reversibility.
The initial step of the E1cb reaction is the N—H bond fission
K
2
ꢀ
¼KNH/Ka ¼3.16 ꢂ10 ¼
O,
2
1
ꢀ1
s
0
, that is kꢀH O << k
2
OH
2
E
kEKNH
kobs ¼kN þkB½Bꢁþ
(14)
aHþ þKNH
[
50]
which may be reversible or rate determining,
and the
expulsion of the aryloxy group occurs subsequently. The b
0
At pH 2, K of Eqn (3) is nearly unity and the minimum of the
pH-rate profile in Fig. 1 indicates the incursion of the water
catalyzed hydrolysis that becomes the main reaction and the
value reflects the extent of proton transfer in the transition
[
51]
state for the catalytic process. In the presence of a buffer the
reaction can be written as Eqn (12) (without considering the
charges on B and BH).
term of the specific base hydrolysis is negligible. In Eqn (14)
kH O½H2Oꢁ¼kN ¼(2.60 ꢅ0.16) ꢂ10 s
first-order rate constant of the water catalysis and k
second-order rate constant of the general base B. The minimum
molarity of the water catalysis is 2 but the exact value cannot be
determined by kinetic methods and will be discussed below.
The free energy profile of Fig. 4 also shows that the catalytic
order of the general bases is due to the stabilization of the initial
state.
ꢀ8 ꢀ1
is the pseudo-
is the
2
B
KB
KE
ꢀ
SH þB ÐBH þS ꢀ!Product
(12)
kꢀBH
There is a complex dependence of the rate on both the pH and
ꢀ
buffer (including water and OH ) concentration, depending on
[
52]
the values of the rate constants k
B
E
, kꢀBH, and k (Eqn 13). The
last term on the right-hand side of Eqn (13) is a consequence that
the catalytic constants k and k , and the dissociation constant
B
ꢀBH
of the substrate KNH, are not independent.
Protium–deuterium exchange reaction of the NH bond
P
P
1
The exchange was measured at 50 8C in D
2
O by H NMR
kE
kB½Bꢁ
kEKNH
kB½Bꢁ
kobs ¼ P
¼
P
(13)
observing the disappearance of the signal at 9.5 ppm and
produced a typical first-order kinetics, with a rate constant k
kE þ
kꢀBH½BHꢁ
kEKNH þaH
þ
kB½Bꢁ
ex
ꢀ
3
ꢀ1
The rate depends on the N-deprotonation energy barrier
DG and the elimination barrier DG which is constant. The free
(5.4 ꢅ2.2) ꢂ10
s
at 50 8C, that reached the equilibrium state
6
¼
6¼
SH
in 20 min.
SH
energy profile of Fig. 4 assumes that for the hydroxide ion k is
Isotope-exchange reactions have a potential-energy surface
that is symmetric with respect to reactants and products for any
mechanism and consequently no detailed description can be
obtained from these results. It is assumed that the solution is so
diluted that the isotopic composition of the solvent may be
independent of the solvation and exchange of the solute. If A and
B are the molecules between which the exchange is taking place,
OH
4
5
ꢀ1 ꢀ1
and, in the absence of buffer, ko
of the order of 10 –10 M s
obs
is given by Eqn (9), because the specific base hydrolysis is the
main reaction. The linear Brønsted plot and the linear effect of the
general base concentration suggest that at pH ꢆ2 the terms
P
P
kE ꢇ
kꢀBH½BHꢁor kEKNH ꢇa
þ
kB½Bꢁ, because always the
H
molarities [BH] and [B] are less than 1. Therefore, Eqn (13)
J. Phys. Org. Chem. 2010, 23 915–924
Copyright ß 2010 John Wiley & Sons, Ltd.
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E. HUMERES, E. P. DE SOUZA AND N. A. DEBACHER
[
59,60]
and a and b are the amount of the corresponding molecules, the
effective rate constant for approach to equilibrium is the sum of
the rate constants of the two opposite reactions given by Eqn (15)
where <is the gross rate of exchange.
the transition-state contribution TSC (Eqn 16).
The analysis is
facilitated by the fact that the thioncarbamate has only one
exchangeable proton.
ðTSCÞ
n
ꢂ ꢃ
kn ¼ko
(16)
1
1
ðRSCÞ
n
kex ¼
þ
<
(15)
a
b
The possible transition state model I assumes that the N to O
transfer occurs including a second water molecule and the
Gross–Butler equation has the form of Eqn (17), where f are the
i
corresponding fractionation factors. There are three hydrogens
(O-L , O-L , O-L ) experiencing some change in bonding
contributing to the secondary SIE, and two ‘in flight’ protons
(N-L -O and O-L -O) being transferred at the transition state, and
When a << b (e.g. b is the solvent), the rate in the direction A!B
[
53,54]
is kex ¼<=a.
The gross rate of exchange should have the
same magnitude as the rate constant of the water catalyzed
ꢀ
8
ꢀ1
s ,
reaction k ¼(2.60 ꢅ0.16) ꢂ10
and the value of
ꢀ1
s is consistent with the concentration
N
3
4
5
ꢀ
3
k
ex ¼(5.4 ꢅ2.2) ꢂ10
ꢀ5
of the substrate used for the NMR determination (ca. 10 M).
1
2
contributing to the primary SIE. The mechanism of proton
abstraction for the series of monobasic species of the Brønsted
plot should be the same and, therefore, the transition state of the
Kinetic solvent isotope effect and proton inventory
The rate constant of the water catalyzed reaction k
at pH 2. The pH-rate profile showed that the contribution of the
specific acid and base catalysis in k is only within the error range
N
was measured
[61]
water catalyzed reaction does not include water linking rings.
N
ꢀ8
ꢀ8
(
0.1ꢂ10 and 0.01ꢂ10 , respectively). Also the water point
falls on the Brønsted line of the general base catalysis plot. If the
O-arylthioncarbamate behaves as a weak acid and decomposes by
water catalysis through an N to O proton transfer mechanism,
proton inventory could give an insight into the structure of the
transition state involved and the mechanism of the reaction. The
results of the proton inventory are shown in Table 3.
0
ꢀ
ꢁ1 0ꢀ
ꢁ1
T3
OꢀL3
T4
OꢀL4
1
ꢀn þnf
1 ꢀn þnf
The inverse solvent isotope effect for general base catalysis is
consistent with a partial transfer of the proton at a rather late
transition state as was suggested by the Brønsted plot and it is
@
A @
A
kn ¼k0 ꢄ
ꢂ
ꢅ
ꢄ
ꢅ
1 ꢀn þnfOꢀL3
1 ꢀn þnfOꢀL4
sec
sec
!
T5
[
55–58]
ð1 ꢀn þnf
Þ
expected for a transfer between N to (or from) O.
The water
OꢀL5
(17)
catalyzed rate constant in protium oxide of EMeOT, k ¼k ,
ð1 ꢀn þnfOꢀL
N
o
5
sec
D
o
H
o
ꢀ
ꢁꢀ
ꢁ
exhibits an inverse SIE k =k ¼2.76. For reactions with net
0
1
A
T1
T2
1
ꢀn þnf
1 ꢀn þnf
1 ꢀn þnfNꢀL1 1 ꢀn þnfOꢀL2
inverse SIE, bulging down plots of k
existence of a multiproton transition state. The function k
n
versus X
D
always indicate the
(n) can
NꢀL1ꢀO
OꢀL2ꢀO
ꢂ ꢄ
@
ꢅꢄ
ꢅ
n
pri
be expressed in terms of the reactant-state contribution RSC, and
Whether there are one or two molecules involved in the TS
þ
depends on considering that only a simple hydron H
3
O
is
Table 3. Proton inventory of the water catalyzed reaction of
a
formed or if it is assumed that there are several water molecules
EMeOT at 50 8C
þ
solvating the hydron (H9O ). In this latter model the transfer
4
occurs to a second (or outer) molecule bound by hydrogen
bonding. This is an indirect proton transfer from the N—H bond
to the final hydron through a water molecule that acts as an
intermediary. Single hydron formation is favored if we assume
that the log of the rate of reaction is influenced by a factor b,
according to the Brønsted catalysis law, where b is a measure of
the transfer. Brønsted b ¼0.63 value indicates that proton
transfer is advanced but not complete in the TS and, con-
sequently, general catalysis can be observed. Indirect hydron
formation is more complex and it needs lower fractionation
factor for the TS involved. The model with two water molecules
represents an indirect proton transfer. A clear distinction is not
possible between the two models although the simpler should be
preferred.
8
calcd ꢀ1 b
(s )
1
0 k
n
8
exp ꢀ1
)
xD
10 kn (s
n ¼2
n ¼3
n ¼4
n ¼5
0
0
0
0
0
0
0
0
0
0
1
.000
2.60 ꢅ0.16
2.81 ꢅ0.10
3.02 ꢅ0.13
3.27 ꢅ0.11
3.71 ꢅ0.21
3.52 ꢅ0.29
4.79 ꢅ0.14
5.03 ꢅ0.23
6.06 ꢅ0.19
7.13 ꢅ0.25
2.72
2.76
3.02
3.02
3.69
3.69
4.58
5.40
6.18
7.00
7.05
2.59
2.83
3.14
3.14
3.68
3.68
4.46
5.27
6.11
7.09
7.16
0.991
1.72
2.61
2.79
3.13
3.13
3.72
3.72
4.46
5.23
6.07
7.10
7.18
0.991
1.82
2.59
2.87
3.08
3.08
3.72
3.72
4.53
5.23
5.99
7.11
7.20
0.992
1.88
.142
.303
.303
.503
.503
.678
.802
.901
.994
.000
The functional groups involved in the reactants are >N—L
c
7.18
[59]
(f
¼0.92) and L O (f ¼1.0);
OꢀL
therefore, in Eqn (16) the
(Eqn 18).
NꢀL
2
2
R
0.986
1.94
RSC term becomes only 1 ꢀn þnf
9
NꢀL1
1
0 SD
a
b
c
ðTSCÞ
n
In 0.01 M L
2
SO
4
at 50.0 8C.
kn ¼ko ꢄ
ꢅ
(18)
ꢀ
ꢁ
1
ꢀn þnf
NꢀL1
Considering RSC ¼ 1 ꢀn þnf
Extrapolated.
, f
¼0.92.
NꢀL1
NꢀL1
The term koðTSCÞ can be expressed as a polynomial in n of
n
[
59,60]
order n,
where the order of the polynomial indicates the
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Copyright ß 2010 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2010, 23 915–924

HYDROLYSIS OF N-ALKYL O-ARYLTHIONCARBAMATE ESTERS
number of hydrogenic sites whose state has been altered on
going from the ground state to the transition state (Eqn 19).
participation of L in-flight and two equivalent protons L and L
1 2
(Eqn 21b).
3
ꢄ
ꢅ
n
ꢄ
ꢅ
X
Therefore, the proton inventory curve can be described as the
kn 1 ꢀn þnf
NꢀL1
n
kn 1 ꢀn þnf
¼koðTSCÞ ¼ko þ
cnn
(19)
ꢀ
ꢁ ꢀ
ꢁ
NꢀL1
n
T3
OꢀL3
T1
1
¼k0 1 ꢀn þnf
1 ꢀn þnf
NꢀL1ꢀO
(
21a)
sec
ꢁ
pri
ꢀ
T2
ꢂ 1 ꢀn þnf
OꢀL2ꢀO
fifth-order polynomial shown in Eqn (20).
pri
ꢄ
ꢅ
ꢄ
ꢅ
kn 1 ꢀn þnf
kn 1 ꢀn þnf
¼
NꢀL1
NꢀL1
ꢀ
ꢁ ꢀ
ꢁ
2
2
3
4
5
T3
OꢀLi
T1
ko þc1n þc2n þc3n þc4n þc5n
(20)
¼k0 1 ꢀn þnf
1 ꢀn þnf
(21b)
NꢀL ꢀO
1
sec
pri
The agreement of the calculated values of k
experimental values shown in Table 3 is consistent with
the assumption that there are several protons involved in the
n
with the
where i ¼2, 3.
Executing the parentheses on the right-hand side of Eqn (21a)
and matching the identities of the C coefficients with the
proper order in the polynomial of Eqn (20), Eqns (22) were
obtained that were solved for the fractionations factors f , giving
i
2
transition state. The precision R increased with the number of
terms or atoms involved but the standard deviation presents a
minimum for n ¼3 that favors the assumption that there are
three active protons (Fig. 5). The precision of the measurements
of the rate constants is not enough for distinguishing between
three or four protons; however, the standard deviation is one of
i
T1
T
L2
T
L3
f
¼2.59 ꢅ0.03 and f ¼f ¼0.53 ꢅ0.56, suggesting
NꢀL1ꢀO
that protons L and L3 are equivalents and consequently
2
Eqn (21b) describes better the mathematical model. Considering
that fT ¼f , Eqns (21b) and (22) produced f
T
T1
¼
L2
L3
NꢀL1ꢀO
[
62]
T
T
L3
the best criteria for the prediction.
The reaction under these
2.23 ꢅ0.97 and f ¼f ¼0.71 ꢅ0.22.
L2
conditions has a half-life of 309 days and could only be studied
measuring the 5% of the initial rate (23 days). We will concentrate
the discussion on the mathematical model with three contribut-
ing protons.
T
L2
T
T1
C1 ¼k0ðf þf þf
ꢀ3Þ
L3
T
NꢀL1ꢀO
T
L3
T1
T
T
T
T1
C2 ¼k0½3 ꢀ2ðf þf þf
Þþf f þf f
L2 NꢀL1ꢀO
L2
NꢀL1ꢀO
L2 L3
T
T1
þf f
ꢁ
L3 NꢀL1ꢀO
The observed Brønsted b value and the highly negative
T
T
L3
T1
T
T
T
T1
C3 ¼k0½f þf þf
ꢀðf f þf f
L2
NꢀL1ꢀO
L2 L3
L2 NꢀL1ꢀO
entropy of activation found for the water catalysis
T
T1
T
T
T1
þf f
Þþf f f
ꢀ1ꢁ
ꢀ31 cal Kꢀ1 mol , Table 1) supports the conclusion of a late
ꢀ1
L3 NꢀL1ꢀO
L2 L3 NꢀL1ꢀO
(
(
22)
transition state because the high polarity would produce an
electrostriction of the solvation layer enforcing the water
molecules to be tightly constrained. This effect was also observed
In the transition state of Scheme 4 the L proton, in transit to a
water molecule, contributes to a primary isotope effect, and the
two protons L and L contribute to a secondary isotope effect.
The f values of these protons are dependent on the Brønsted
1
[
20]
in alkyl N-alkylthioncarbamate esters, carboxylic ester hydroly-
2
3
[
63]
sis,
and in water catalyzed reactions with multiple protons
i
[
64]
T
Li
transition state.
b value. The transition state fractionation factor f ¼0.79 for
If there are three active protons at the TS the incipient hydron
L L L O could transfer the charge on the oxygen to the nearest
each L and L was calculated from the Brønsted value in Eqn
2
3
þ
[65]
1
2 3
(23).
2
water molecule through the O to O transfer of L . This mechanism
would imply three different hydrogenic sites altered in the TS
with two protons in transit, with different fractionation factors
ꢀ
ꢁ ꢀ ꢁ
1
ꢀb
b
TS
Li
RS
Li
PS
Li
f
¼
f
f
(23)
(
Eqn 21a), while the formation of only the hydron would have the
These values indicate the extent of development of hydron
character of the water molecule that is acting as a general base in
[
66]
RS
the transition state. For the reactant state fLi ¼1 and for the
PS
T
Li
8
7
6
5
4
3
2
full hydron fLi ¼0.69. The fractionation factor f ¼0.79
indicates that the hydron is ca. 68% developed at the transition
state, in good agreement with the value calculated from the
mathematical model. Protons L
belong to the incipient hydron. Gem-diol protons present
fractionation factors’ values in the range of 1.25–1.33.
These data should be compared to the value of the SIE
2 3
and L are not gem-diols but
[
59,62,64]
D
o
H
o
k =k ¼k1=ko. When n ¼1, Eqn (21b) becomes Eqn (24). The
T
Li
T1
values obtained above for f and f
predict an inverse
NꢀL1ꢀO
SIE of 1.7 ꢅ1.3 that is consistent with the experimental SIE,
although not very satisfactory due to the error from the kinetics
measurements.
ꢀ
ꢁꢀ
ꢁ
2
T
T1
f
f
k1
OꢀLi
NꢀL1ꢀO
0.0
0.2
0.4
0.6
0.8
1.0
¼
(24)
XD
ko
f
NꢀL1
T1
A value of f
> 1 indicates a proton with binding
Figure 5. Proton inventory of the water catalyzed reaction of the
NꢀL1ꢀO
[
59]
hydrolysis of EMeOT at 50 8C in 0.01 M L
was drawn for order n ¼3.
2
SO
4
. The continuous curve
potentials tighter than those in the bulk solvent.
Also, for
T
i
T
T
isotope exchange ꢀDG ¼RT ln f and if for the TS f > 1 and for
i
i
J. Phys. Org. Chem. 2010, 23 915–924
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E. HUMERES, E. P. DE SOUZA AND N. A. DEBACHER
ꢀ
1
ꢀ1
K ) is within the range for a unimolecular
(
ꢀ8 cal mol
mechanism. At high basicity the rate constants reach a constant
value indicating that the expulsion of the aryloxide is not
concerted.
The neutral species hydrolyzes with general base catalysis with
Brønsted b ¼0.63 ꢅ0.07. Water acts as a general base catalyst
ꢀ
8
ꢀ1
s . The
with (pseudo-) first-order rate constant k
N
¼2.6 ꢂ10
D
H
inverse kinetic solvent isotope effect of k =k ¼2.76 is consistent
o
o
with a transfer of the N—H proton at a late transition state,
supported also by the highly negative entropy of activation
ꢀ
1
ꢀ1
(
ꢀ31 cal K mol ).
The proton inventory showed a bulging down plot that
indicates a multiproton transition state, and the polynomial
expression of k favors the assumption that there are three active
n
protons. The N to O proton transfer to the water molecule form an
incipient hydron that is ca. 68% developed at the transition state.
EXPERIMENTAL SECTION
Materials
Reagents were all of analytical grade and were used without
further purification. Distilled water was deionized and deox-
ygenated by boiling and cooling under nitrogen.
Ethylisothiocyanate
Ethylisothiocyanate was obtained from the reaction of ethyl-
amine in THF with CS2 and
triethylamine; bp 133 8C; UV, lmax (water) 240 nm [lit. bp
131–132 8C; UV, lmax (dioxane) 245 nm].
a
catalytic amount of
Scheme 4. Mechanism of the water catalyzed hydrolysis
[
71]
[
72]
R
reactants f < 1, the change of free energy of isotope exchange
i
T
o
T
should be DG > DG and consequently k1 ꢇko producing an
1
[
65]
[27]
inverse SIE. It means that the proton in the TS side has higher
N-ethyl O-p-methoxyphenylthioncarbamate, EMeOT
[
53]
vibrational frequencies than on the reactant side.
The high
T1
p-Methoxyphenol (51.0 g; 0.41 mol) was dissolved in 150 ml of
dichloromethane, and a solution of ethylisothiocyanate (40.0 g;
value of f
(2.23 ꢅ0.97) is similar to that found for the acid
NꢀL1ꢀO
[
67–69]
catalyzed hydration of olefins.
In this case, the fractionation
0
.46 mol) and 20 ml of triethylamine in 150 ml of dichloro-
factor for the in-flight proton (that should be the same for reverse
reaction of abstraction of a proton from a very weak acid by a
water molecule to form a hydron) was calculated to be 3.9 ꢅ0.2.
The reaction of weak carbon acids with methoxide ion
occurred with inverse SIE and bulged down proton inventory
curves. The TS is very product-like and the proton is almost
methane was added. After the addition of 250 ml of 0.06 M
phosphate buffer, pH 7, the heterogeneous mixture was
vigorously stirred at room temperature for 72 h. The organic
layer was separated and the aqueous layer was extracted with
dichloromethane. The final organic extracts were dried over
magnesium sulfate, filtered and the dichloromethane was
eliminated in a rotatory evaporator. A sample of 12.5 g of the
product was chromatographed in a silica column and was eluted
with a solution of hexane: dichloromethane 80:20. The fraction
was concentrated under vacuum and 6 g of a white solid was
[
70]
completely transferred to the base.
The SIE rises from the
change of hydrogen bonding of solvation of the base in the
transition state. The N—H bond of the thioncarbamate ester is a
weak acid and has the only exchangeable proton. In the TS
there is one proton in-flight to the reacting water molecule while
the other two hydrogen bonding with the bulk solvent are
transformed, as the hydron is formed, so the fractionation factor
of the two protons decreases from 1 to 0.69.
obtained that was recrystallized in ethanol; mp 76–77 8C [lit.
[27]
7
7.0 8C] ; UV, lmax (water) 244 and 274 nm (shoulder); lmax
(
2 2
CH Cl ) 248 and 274 nm (shoulder).
CONCLUSIONS
The acid hydrolysis of N-ethyl O-p-methoxyphenylthioncarbamate
(
EMeOT) occurs by an A1 mechanism: the excess acidity plot
against X was linear with slope 0.93, and the Bunnett–Olsen
coefficient was f 0.07.
1
3
[27]
C NMR (CDCl ), at 22 8C, d(ppm): 190.0 (CS) [lit. 189.7;
3
[
23]
[73]
¼6
189.9;
189.6 ], 157.7 (C-4), 147.4–146.9 (C-1), 123.8–123.4
The basic hydrolysis of EMeOT is faster than N-ethyl
O-ethylthioncarbamate that hydrolyzes by the E1cb mechanism.
The difference in reactivity is only consistent if the mechanism
is also E1cb. The small negative entropy of activation
3 2
(C-2,6), 114.5 (C-3,5), 55.8 (p-CH O), 40.9–39.3 (CH ), 14.6–13.9
(CH3).
The carbons of the N-alkyl group presented two signals as well
as the carbons 1, 2, 6 of the aryl moiety. The chemical shifts in the
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Copyright ß 2010 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2010, 23 915–924

HYDROLYSIS OF N-ALKYL O-ARYLTHIONCARBAMATE ESTERS
temperature range of 22–52 8C showed very little dependency.
The double signals are not due to a partial hydrolysis of EMeOT
as was observed by comparison to the spectrum of
equilibrium was reached after 20 min. This time was considered
before starting the rate measurements of the isotope effect.
p-methoxiphenol.
1
Kinetics solvent isotope effect and proton inventory
H NMR (CDCl
3
), d(ppm): (7.38, trans)-(6.78, cis) (s, NH), 6.99 (m,
O), 3.49–3.63 (quintet, CH ),
C-2,6), 6.90 (m, C-3,5), 3.80 (s, p-CH
.27–1.24 (t, CH
1
3
2
Proton inventory of the water catalyzed hydrolysis of EMeOT was
studied at 50 8C in 0.01 M L SO adding 3 ml of the solution of the
1
3
).
H NMR spectrum of EMeOT shows clear evidence for the
2
4
substrate in DMSO. The samples were thermostated for 20 min at
0 8C and then the kinetics were followed at 288 nm. The rate
constants were calculated from the initial rates. The solvent for
the samples was obtained from stock solutions of 0.01 M D SO in
O and 0.01 M de H SO in H O which were mixed and weighted
in 10 ml volumetric flasks using septa to avoid atmospheric
humidity. The deuterium content of the 0.01 M D SO solution
[
74,75]
co-existence of two isomeric forms.
Each of the types of
5
proton exhibits two signals except the p-methoxy group. By
integration of the NH signals it was found that the isomer ratio in
carbon tetrachloride was 7:3, therefore, the cis isomer pre-
dominates (the terms cis and trans are used to designate the
2
4
D
2
2
4
2
[
75]
relationship of the thiocarbonyl sulfur and the N-alkyl group).
2
4
1
was calculated by H NMR using acetone as an internal standard.
Kinetics
The rate constants of the hydrolysis of EMeOT were obtained
at pH >7 by the appearance of p-methoxyphenolate at l 306 nm,
Activation parameters
and at pH <7 at
l
288 nm by the appearance of
Activation parameters were calculated from the rate constants in
the range of 35.0–50.0 8C by least-square fitting to the Eyring
equation.
p-methoxyphenol. The fastest reactions were followed for
more than four half-lives and the first-order rate constants
were calculated by the spectrophotometer software. The rate
constants of the slow reactions were obtained by the initial rate
method according to Eqn (25).
Acknowledgements
kobs ¼ðDA=DtÞð1=DꢀÞð1=CoÞ
(25)
The scholarship for E. P. de S. and the research fellowship for E. H.
from the Brazilian Conselho Nacional de Pesquisa Cient ´ı fica e
Tecnol o´ gica (CNPq) are gratefully acknowledged.
where DA/Dt is the slope of the plot absorbance versus time;
De ¼ephenol ꢀethion is the difference between the molar
absorptivities at 288 nm of the p-methoxyphenol (ephenol 4435)
and EMeOT (ethion 384), respectively; C is the initial concentration
o
calculated from C
zero extrapolated from the regression line.
o
¼A
o
/ethion; and A
o
is the absorbance at time
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J. Phys. Org. Chem. 2010, 23 915–924
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J. Phys. Org. Chem. 2010, 23 915–924