Hydrolysis of N-aryl thioncarbamate esters. Modified Marcus equation for reactions with asymmetric intrinsic barriers

Article abstract of DOI:10.1002/poc.517

The hydrolysis of ethyl N-p-substituted arylthioncarbamates was studied at 100°C in the pH range 6.5-12.5. No general catalysis was found, and the presence of an isothiocyanate intermediate was detected, indicating that the alkaline hydrolysis occurs by an E1cb mechanism. From the pH-rate profiles, the first-order rate constants k_E for the elimination step of the thioncarbamate anion forming the isothiocyanate intermediate were determined. The alkaline hydrolysis of p-substituted arylisothiocyanates was studied at 25°C in 0.1-0.3 M solutions of NaOH and in 0.1-0.3 M aqueous ethanol solutions, at different concentrations of NaOH. The second-order rate constants for the addition reaction with hydroxide (k_OH) and ethoxide (k_A) ions were obtained. Leffler plots for the elimination of the ethoxide ion from the arylthioncarbamate anion and for the addition of the ethoxide ion to the arylisothiocyanate were linear. From Leffler's equation, with the sole condition that dα_L/dΔG should be constant, a modified Marcus equation (MME) was obtained, where a parameter p (or q for the reverse reaction) defined the asymmetry of the intrinsic barrier. (When p = 1/2 the barrier is symmetric and the MME becomes the Marcus equation in the usual form.) For the addition-elimination reaction studied, both Leffler plots were adjusted to MME with the asymmetric parameter p = 0.694 ± 0.002 for the addition and q = 0.307 ± 0.002 for the elimination reaction. The intrinsic barrier was ΔG₀^≠ = 24.75 ± 0.02 kcal mol^-1 and |ΔG_max| = 438 ± 4 kcal mol^-1 (1 kcal = 4.184 kJ). The addition reaction was exoergic and, as expected from the high intrinsic barrier, α_L changed very little in the series (0.679-0.683); the transition state was product-like, and it moved towards the reagents with increasing exoergicity. Copyright

Full text of DOI:10.1002/poc.517

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2002; 15: 570–575
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.517
Hydrolysis of N-aryl thioncarbamate esters. Modi®ed
Marcus equation for reactions with asymmetric intrinsic
barriers†
Eduardo Humeres,1,2* Cesar Zucco,1 Mauricea Nunes,1 Nito A. Debacher1 and Ricardo J. Nunes1
1Departamento de QuõÂmica, Universidade Federal de Santa Catarina, 88040-900 Floriano polis, SC, Brazil
2Institute for Fundamental Research in Organic Chemistry, Kyushu University, Hakozaki, Fukuoka 812-8581 Japan
Received 28 September 2001; revised 26 February 2002; accepted 1 March 2002
ABSTRACT: The hydrolysis of ethyl N-p-substituted arylthioncarbamates was studied at 100°C in the pH range
6.5–12.5. No general catalysis was found, and the presence of an isothiocyanate intermediate was detected, indicating
that the alkaline hydrolysis occurs by an E1cb mechanism. From the pH–rate profiles, the first-order rate constants kE
for the elimination step of the thioncarbamate anion forming the isothiocyanate intermediate were determined. The
alkaline hydrolysis of p-substituted arylisothiocyanates was studied at 25°C in 0.1–0.3 M solutions of NaOH and in
0.1–0.3 M aqueous ethanol solutions, at different concentrations of NaOH. The second-order rate constants for the
addition reaction with hydroxide (kOH) and ethoxide (kA) ions were obtained. Leffler plots for the elimination of the
ethoxide ion from the arylthioncarbamate anion and for the addition of the ethoxide ion to the arylisothiocyanate were
linear. From Leffler’s equation, with the sole condition that daL/dDG should be constant, a modified Marcus equation
(MME) was obtained, where a parameter p (or q for the reverse reaction) defined the asymmetry of the intrinsic
barrier. (When p = 1/2 the barrier is symmetric and the MME becomes the Marcus equation in the usual form.) For the
addition–elimination reaction studied, both Leffler plots were adjusted to MME with the asymmetric parameter
p = 0.694 Æ 0.002 for the addition and q = 0.307 Æ 0.002 for the elimination reaction. The intrinsic barrier was
ˆ
ÁG0 ˆ 24:75 Æ 0:02 kcal molÀ1 and jDGmaxj = 438 Æ 4 kcal molÀ1 (1 kcal = 4.184 kJ). The addition reaction was
exoergic and, as expected from the high intrinsic barrier, aL changed very little in the series (0.679–0.683); the
transition state was product-like, and it moved towards the reagents with increasing exoergicity. Copyright  2002
John Wiley & Sons, Ltd.
KEYWORDS: arylthioncarbamates; arylisothiocyanates; hydrolysis; Marcus equation
INTRODUCTION
of reactions (1) has been used to immobilize an enzyme
(Enz-NH2) to a cellulose matrix [Cel-OC(S)SR] because
of the stability of the thioncarbamate group towards
hydrolysis.4
The reactions of carbon disulfide present a close
parallelism with carbon dioxide.1 Some of the products
of the reaction with alkoxides, halides and amines [Eqn.
(1)] have important biological activity as pesticides.2 The
different reactivities of these oxo and sulfo derivatives
are a consequence of the characteristics of the C—X bond
involved. For instance, oxygen can stabilize a-carbo-
cations better than sulfur, but this capacity is inverted for
carboanions. Sulfur can accept electrons in the empty 3d
orbital much better than oxygen, and consequently the
thiocarbonyl group is a powerful electron sink.3 The
reaction of esters 1 with amines produces carbamic
(X = O) or thioncarbamic (X = S) esters 2. The sequence
In this work, we studied the mechanism of hydrolysis
of ethyl N-arylthioncarbamate esters and the correspond-
ing arylisothiocyanates that are formed as intermediates.
The results allowed the calculation of the rate and
equilibrium constants for a one-step addition–elimination
reaction that can be analyzed in terms of the Marcus
formalism.
*Correspondence to: E. Humeres, Departamento de Qu´ımica,
Universidade Federal de Santa Catarina, 88040-900 Floriano´polis,
SC, Brazil.
EXPERIMENTAL
E-mail: humeres@mbox1.ufsc.br
†Presented at the 8th European Symposium on Organic Reactivity
(ESOR-8), Cavtat (Dubrovnik), Croatia, September 2001.
Materials. All reagents were of analytical grade. Distilled
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 570–575

HYDROLYSIS OF N-ARYL THIONCARBAMATE ESTERS
571
water was deoxygenated by boiling and cooling under
nitrogen. UV spectra and kinetics were measured using a
Cary 219 spectrophotometer. All compounds were
extracted with diethyl ether and recrystallized from the
same solvent: m.p. 26–28°C (lit.8 25–26°C); lmax
(EtOH), 269, 280 nm.
1
identified by H NMR and IR spectra.
p-Methoxyphenylisothiocyanate8. The procedure was
the same as for p-methylphenylisothiocyanate: bp 279–
281°C (lit.9 280–281°C); lmax (EtOH) 273, 285 nm.
Phenylisothiocyanate5,6. Carbon disulfide (1.3 mol) and
1.3 mol of ammonia solution (sp. gr. 0.9) were cooled on
ice, 0.6 mol of aniline was added with magnetic stirring
and the solution was allowed to react for 30 min. After
standing for 30 min, the precipitate of ammonium
phenyldithiocarbamate was filtered off and dissolved in
800 ml of water. A solution of 0.6 mol of lead sulfide in
400 ml of water was added and the mixture was steam
distilled, collecting the distillate in 0.5 M sulfuric acid.
The oil was separated, dried over CaCl2 and distilled
under vacuum: b.p. 119–121°C/35 mmHg (lit.5 120–
121°C/35 mmHg); lmax (water), 265, 273 nm.
p-Hydroxyphenylisothiocyanate8. p-Aminophenol (0.1
mol) was stirred with 120 ml of 1 M HCl and 0.1 mol of
thiophosgene was added dropwise. The mixture was
mechanically stirred for 7 h at room temperature. The
oily product was extracted with diethyl ether, the solution
was dried over CaSO4 and the solvent was evaporated
under vacuum: TLC, Rf 0.5 (benzene); after molecular
distillation, the same Rf was found; b.p. 210°C; lmax
(water), 310, 330 nm.
p-N,N-Dimethylphenylisothiocyanate. The procedure
was the same as for phenylisothiocyanate. The solid
product was dried under vacuum over P2O5 and re-
crystallized from anhydrous ethanol: m.p. 67–68°C; lmax
(water), 295 nm.
Ethyl N-arylthioncarbamates8,10
. A 1 mol amount of the
corresponding arylisothiocyanate was dissolved in 10 mol
of anhydrous ethanol and the mixture was boiled under
reflux. The product was crystallized at room temperature
and recrystallized from light petroleum (b.p. 40–60°C).
Phenyl: m.p. 68–69°C (lit. 69–71°C11; 70–71°C10); lmax
(water), 272 nm. p-Nitro: m.p. 176–177°C (lit.10 175°C);
lmax (EtOH) 336 nm. p-Chloro: m.p. 104–105°C (lit.11
104–106°C); lmax (water), 276 nm. p-Methyl: m.p. 83–
84°C (lit.10 85°C); lmax (water), 272 nm. p-Methoxy:
m.p. 78–80°C (lit.12 81°C); lmax (water), 273 nm.
p-Chlorophenylisothiocyanate7. Carbon disulfide (0.35
mol), 0.6 mol of ammonia solution (sp. gr. 0.9) and
0.30 mol of p-chloroaniline were mechanically stirred for
1 h at 30–35°C. The product was filtered off, washed
with a 3% solution of ammonium chloride followed by
ethanol and suspended in 250 ml of water at 30°C. A
solution of 0.15 mol of chloroacetic acid and 0.075 mol
of sodium carbonate in 35 ml of water was added with
stirring. After cooling to room temperature, a solution of
0.15 mol of ZnCl2 in 75 ml of water was added dropwise,
with vigorous stirring, for a period of 1 h, maintaining the
pH at 7 by the addition of ammonia solution. The product
was filtered off and dried under vacuum over P2O5, and
then extracted with light petroleum (b.p. 30–60°C). The
solvent was evaporated under vacuum and the isothio-
cyanate was recrystallized from ethanol: m.p. 43–45°C
(lit.7 44–45°C); lmax (aq. EtOH), 272, 283 nm.
Acid dissociation constants of ethyl N-arylthioncarba-
mates. The dissociation constants were calculated at
25°C from a series of measurements of the absorbance at
l
max of solutions of ca 10À5 M of the substrate in the pH
range 6–13. The UV spectra showed one isosbestic point.
Inversion of the pH after the titration showed that the
dissociations were reversible with no noticeable reaction
at 25°C.
Product analysis. The products of the hydrolysis of
phenylthioncarbamate were characterized in a prepara-
tive run at 0.1 M NaOH and 100°C. The samples were
submitted to molecular distillation. Ethanol was identi-
fied by liquid chromatography (Porapak Q column,
157°C) from the distilled fraction. Aniline was identified
from the UV spectrum, from TLC [hexane–acetone (7:3)]
and from Rimini assay.13
In order to trap the isothiocyanate intermediate, a
preparative run of the hydrolysis of phenylthioncarba-
mate was carried out at 100°C and pH 8.2 (measured at
25°C) in the presence of ethylamine. Three samples were
taken at 8 h intervals. The samples were extracted with
chloroform, concentrated in a rotatory evaporator and
then analyzed by TLC [hexane–acetone (7:3)] using
aniline and N-phenyl-N'-ethylthiourea as references. All
the samples gave a positive test for thiourea (Rf 0.37) and
aniline (Rf 0.50).
p-Nitrophenylisothiocyanate8. p-Nitroaniline (0.13 mol)
was stirred with 700 ml of 10% HCl and the hydro-
chloride was filtered off and placed in an Erlenmeyer
flask that was stoppered after adding 0.13 mol of
thiophosgene. The mixture was stirred mechanically
and vigorously for 2 days at room temperature. The pale
yellow product was filtered off and crystallized from
acetone: m.p. 108–110°C (lit.8 112–113°C); lmax (aq.
EtOH), 317 nm.
p-Methylphenylisothiocyanate8. Thiophosgene (0.11
mol) was added dropwise to an equimolecular amount
of p-toluidine dispersed in 250 ml of water, with mech-
anical stirring, and the mixture was allowed to react at
room temperature for 3 days. The oily product was
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 570–575

572
E. HUMERES ET AL.
Kinetics
no reaction was observed after the titration, the reaction
corresponded to the dissociation equilibrium of the N—H
bond. The pKa values for the series of thioncarbamate
esters are given in Table 1.
Hydrolysis of ethyl N-arylthioncarbamates. Kinetics
were studied at 100°C in the pH range 6.5–12.5. The
kinetic solution (50 ml) had a final concentration of ca
10À5 M; samples of 3 ml were placed in sealed glass
ampoules and immersed in a thermostat at 100°C. The
samples were collected at different times and quenched in
a Dewar bath with salted ice. The kinetics were followed
by the disappearance of the arylthioncarbamate, by
reading the absorbance at lmax. All runs were followed
for at least three half-lives and the lnDA vs time plots
produced straight lines that were considered when r ꢀ
0.99. The pH of the buffered solutions was measured at
25°C and corrected to 100°C as described elsewhere.14
The pH (>12) of unbuffered runs was controlled at the
end of the experiment and showed no change.
Alkaline hydrolysis of ethyl N-arylthioncarba-
mates
The reaction was studied at 100°C and the pH–rate
profiles were obtained in the pH range 6.5–12.5. The
hydrolyses of ethyl N-phenyl- and N-p-nitrophenylthio-
carbamates were studied with respect to the catalysis by
the buffer using phosphate, borate and carbonate in the
range 0.01–0.05 M, and no buffer effect was observed.
Therefore, the hydrolysis occurs without general cata-
lysis.
The rate constants increase with the pH reaching a
pH-independent plateau at pH >11. A typical profile is
shown in Fig. 1. This profile is consistent with a BAC2 and
E1cb mechanism. Both have been observed for carba-
mate esters,15,16 but the detection of isothiocyanate as an
intermediate and the absence of general catalysis
supports the theory that these ethyl N-arylthioncarba-
mates hydrolyze through the E1cb mechanism, as has
been found for aryl N-aryl analogs17,18 [Eqn. (2)].
According to this mechanism, the pH–rate profile follows
Eqn. (3), where Ka is the acid dissociation constant of the
N—H bond and kE is the first-order rate constant of the
elimination step. The values of the pKa and kE at 100°C
calculated from the pH–rate profiles of the series of
thioncarbamate esters studied in this work are given in
Table 1.
Hydrolysis of arylisothiocyanates. The alkaline hydro-
lysis of aryisothiocyanates was studied at 25°C in 0.1–
0.3 M solutions of NaOH. The final concentration was
about 10À4 M. The reaction was followed by the dis-
appearance of the isothiocyanate at lmax, except for the
p-nitro-, p-N,N-dimethyl- and phenylisothiocyanate that
were accompanied by product formation. The kinetics
were all pseudo-first order and were measured for more
than three half-lives. The reaction of arylisothiocyanates
with ethoxide ion was studied in 0.1–0.3 M aqueous
ethanol solutions at different concentrations of NaOH.
RESULTS AND DISCUSSION
Acid dissociation constants of ethyl N-arylthion-
carbamates
The acid dissociation constants were obtained at 25°C for
the series of ethyl N-arylthioncarbamates from the
absorbance–pH titration curves. Since one isosbestic
point was found for the UV spectra at different pHs and
kEKa
kobs
ˆ
ꢁ3†
‡
Ka ‡ aH
Table 1. Acid dissociation and rate constants of the alkaline
hydrolysis of ethyl p-substituted arylthioncarbamates
104 kE
a
b
X
sp
pKa
pKa
(l molÀ1 sÀ1 b
)
Hydrolysis of arylisothiocyanates
NO2
C1
0.81
0.24
9.2
10.5
10.8
11.0
11.2
11.5c
11.8c
8.2
9.0
0.91 Æ 0.02
1.30 Æ 0.01
2.02 Æ 0.06
2.45 Æ 0.02
2.23 Æ 0.03
3.43c
The reaction with hydroxide ion produced the thioncar-
bamate anion [Eqn. (4)] that is stable under the reaction
conditions. The pH–rate profiles of the alkaline hydro-
lyses were linear with a slope of ‡1 (Fig. 2). The second-
order rate constants for the reaction are given in Table 2.
H
0.00
9.4
Me
À0.17
À0.29
À0.60
À0.81
9.8
MeO
NMe2
OÀ
9.9
10.1c
10.4c
4.22c
a
Measured at 25°C.
b
c
Calculated from the pH–rate profile at 100°C.
Extrapolated from the Hammett correlation line.
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 570–575

HYDROLYSIS OF N-ARYL THIONCARBAMATE ESTERS
573
Table 2. Second-order rate constants of the solvolysis of
p-substituted arylisothiocyanates at 25°C
X
sp
102 kOH (l molÀ1 sÀ1 a
)
kA (l molÀ1 sÀ1 b
)
NO2
C1
0.81
0.24
99.4 Æ 3.2
19.9 Æ 0.3
10.4 Æ 0.20
6.63 Æ 0.31
6.14 Æ 0.71
4.64 Æ 0.19
0.92 Æ 0.02
24.3 Æ 3.0
4.92 Æ 0.32
3.01 Æ 0.24
1.34 Æ 0.12
1.79 Æ 0.13
0.59 Æ 0.04
0.30 Æ 0.04
H
0.00
Me
À0.17
À0.29
À0.60
À0.81
MeO
NMe2
OÀ
a
[NaOH] = 0.1–0.8 M.
b
[EtOH] = 0.1–03 M; [NaOH] = 0.1–0.3 M; [EtOÀ] from Eqns (5) and (6),
Ke = 1.48 Â 10À2 l molÀ1
.
Figure 1. pH±rate pro®le of the alkaline hydrolysis of ethyl
N-p-methylphenylthioncarbamate at 100°C. The curve was
calculated from Eqn. (3)
one-step elimination–addition reaction (7), where KAE
kA/kE (Fig. 3, Table 3).
=
The reaction with ethoxide ion was studied in alkaline
aqueous ethanol solutions, and the second-order rate
constant kA for the addition of the ethoxide ion was
calculated from the observed rate constant according to
Eqn. (5), where a and b are the concentrations of ethanol
and NaOH in the solution, and Ke is the equilibrium
constant of Eqn. (6) (Table 2).
We will consider first the Leffler equation [Eqn. (8)]:19
ˆ
ꢀG ˆ ꢁL ꢀGP ‡ ꢁ1 À ꢁL†ꢀGR
ꢁ8†
kobs ˆ ꢁkAKea ‡ kOH†b
ꢁ5†
where aL is a parameter that expresses the contribution of
free energy in the transition state. It varies between 0 and
1, and is interpreted as the defining the position of the TS
in the reaction coordinates. There is no condition in the
Leffler equation that GP = GR when aL = 1/2, as has been
interpreted.20,21 In this case, ꢀG≠ = 1/2ꢀ(GP ‡ GR), but it
does not imply that GP must be equal to GR. If GP were
Ke
À
EtOH ‡ OHÀ
EtO ‡ H2O
ꢁ6†
ÀÀÀÀÀÀ*
)ÀÀÀÀÀÀ
Modi®ed Marcus equation
The values of kE for the hydrolyses of the arylthioncar-
bamate anions and kA for the addition of ethoxide ion to
arylisothiocyanates permitted the calculation of the free
energy reaction profiles and equilibrium constants for the
Figure 3. Free energy reaction pro®le of alkaline hydrolysis
of ethyl N-p-chlorophenylthioncarbamate; 3±6, according to
Eqns (2) and (4)
Figure 2. pH±rate pro®le of the alkaline hydrolysis of
N-p-chlorophenylisothiocyanate at 25°C
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 570–575

574
E. HUMERES ET AL.
Table 3. Kinetic and equilibrium parameters for the reaction
shown
intrinsic barrier was obtained:
ꢀ
ꢁ
3
4
ˆ
ÁG0 ˆ
À p jÁGmax
j
ꢁ13†
and by substitution and integration, the result is Eqn.
(14):
ˆ
ˆ
ÁGA
ÁGE
KAE
(l molÀ1 a
DGAE
X
(kcal molÀ1) (kcal molÀ1
)
)
(kcal molÀ1
)
!
NO2
Cl
15.565
16.511
16.802
17.282
17.110
17.768
18.169
28.912
28.648
28.321
28.178
28.247
27.928
27.774
6.06 Â 109 À13.347
7.86 Â 108 À12.137
2.77 Â 108 À11.519
9.68 Â 107 À10.896
1.45 Â 108 À11.137
2.80 Â 107 À10.160
3=4 À p
ˆ
ˆ
ÁG ˆ ÁG0 ‡ pÁG ‡
ÁG2
ꢁ14†
ˆ
H
4ÁG0
Me
MeO
NMe2
OÀ
which is the expression of the modified Marcus equation
(MME). When p = 1/2, the barrier is symmetric and Eqn.
(14) becomes the Marcus equation in the usual form.
1.10 Â 107
À9.605
a
At 25°C; KAE = kA/kE.
ˆ
ˆ
Both Leffler plots of ÁGA vs DGAE and ÁGE vs DGEA
were adjusted to Eqn. (14) with the asymmetric par-
ameter p = 0.694 Æ 0.002 for the direct reaction and
q = 0.307 Æ 0.002 for the reverse reaction. The intrinsic
equal to GR, Eqn. (8) would be expressed as ꢀG≠ =
ꢀGP = ꢀGR, which is meaningless because in this case aL
is undetermined. The condition when aL = 1/2 and
GP = GR applies only when the reaction can be related
to a similar reaction.
ˆ
barrier was ÁG0 = 24.75 Æ 0.02 kcal molÀ1 (1 kcal =
The derivative of Eqn. (8) defines aL = dDG≠/dDG.
Since aL is a continuous, single-valued function of DG,
and assuming that aL is constant for a small change of
DG, upon integration Eqn. (9) is obtained:
ˆ
ˆ
ÁG ˆ ꢁLÁG ‡ ÁG0
ꢁ9†
ˆ
where ÁG0 is the kinetic barrier at DG = 0. In the
formalism of Marcus, this barrier is defined as a constant
called the ‘intrinsic barrier’.22 From Table 3, the Leffler
plots produce Eqns (10) and (11) for the addition and
elimination reaction, respectively (Fig. 4).
ˆ
ÁGA ˆ ꢁ0:686 Æ 0:015†ÁGAE ‡ ꢁ24:75 Æ 0:17†
r ˆ 0:999
ꢁ10†
ꢁ11†
ˆ
ÁGE ˆ ꢁ0:314 Æ 0:015†ÁGEA ‡ ꢁ24:75 Æ 0:17†
r ˆ 0:994
For a large change of DG, assuming that daL/dDG is
constant,20 and therefore that aL changes linearly with
DG, integration leads to Eqn. (12):
ꢀ
ꢁ
ÁG
ÀÁG
ꢁL ˆ
‡ p
and ꢂL ˆ
‡ q
ꢁ12†
2jÁGmax
j
2jÁGmaxj
where jDGmaxj is the absolute value of the maximum
barrier and p (or q for the reverse reaction) is a parameter
that measures the asymmetry of the barrier. The barrier is
symmetrical only when p = 1/2 and DG = 0. Substituting
aL and integrating the differential dDG≠ = aLdDG, Eqn.
(13) for the relationship between jDGmax j and the
Figure 4. Lef¯er plots for the addition±elimination reaction:
&, p-X-phenylisothiocyanates ‡ EtOÀ; *, p-X-phenylthion-
carbamate anions
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 570–575

HYDROLYSIS OF N-ARYL THIONCARBAMATE ESTERS
575
tion. Chemical Society: London, 1976; (c) Cremlyn RJ. Pesticides.
Preparation and Mode of Action. Wiley: Chichester, 1978; (d)
Corbett JR, Wright K, Baillie AC. The Biochemical Mode of
Action of Pesticides. Academic Press: London, 1984.
3. Humeres E, Debacher NA, Sierra MM de S, Franco JD, Schutz A.
J. Org. Chem. 1998; 63: 1598–1603.
4. Humeres E, Sequinel LF, Nunes M, Oliveira CMS, Barrie PJ. J.
Phys. Org. Chem. 1994; 7: 287–295.
5. Dains FB, Brewster RQ, Olander CP. Org. Synth., Coll. Vol. 1941;
1: 447–449.
6. Vogel AI. Organic Chemistry. Longmans: London, 1966; 681.
7. Van der Kerk GJM, Pluygers CW, de Vries G. Org. Synth., Coll.
Vol. 1973; 5: 223–226.
8. Browne DW, Dyson GM. J. Chem. Soc. 1931; 3285–3308.
9. Sakai S, Fujimani T, Aizama T S. Bull. Chem. Soc. Jpn. 1975; 48:
2981–2982.
10. Bost RW, Andrews ER. J. Am. Chem. Soc. 1943; 65: 900–901.
11. Mull RP. J. Am. Chem. Soc. 1955; 77: 581–583.
12. Burrows AA, Hunter L. J. Chem. Soc. 1952; 4118–4122.
13. Schupp III, Orion E. Techniques of Organic Chemistry: Gas
Chromatography, vol. 13. Interscience: New York, 1968.
14. Humeres E, Quijano J, Sierra MM de S. J. Braz. Chem. Soc. 1990;
1: 99–104.
15. Dittert LW, Higuchi R. J. Pharm. Sci. 1963; 52: 852–857.
16. Hegarthy AF, Frost LN. J. Chem. Soc., Chem. Commun. 1972;
500–501.
4.184 kJ). Leffler and MME plots produce the same value
for the intrinsic barrier. However, the slope of the Leffler
plot is interpreted as an average of the aL changes in the
series, whereas when the MME is considered, the
adjustment indicates the asymmetry of the kinetic barrier.
The situation is similar to the comparison of a Brønsted
plot and the Marcus equation for proton transfer.
The addition reaction is exoergic and the transition
state is more product like on the aL scale. As expected
from the high intrinsic barrier, the maximum barrier is
438 Æ 4 kcal molÀ1, aL changes very little in the series
(0.679–0.683) and according to the Leffler–Hammond
hypothesis it moves towards the reagents with increasing
exoergicity.
It has been contended that for a reaction series that
does not possess an identity set such as cation–anion
recombination and nucleophilic addition to unsaturated
systems, an intrinsic barrier cannot be determined, and
consequently the Marcus equation23 cannot be satisfied,
but this is true only when considering symmetric barriers.
17. Sartore G, Bregon M, Calmon JP. Tetrahedron Lett. 1974; 36:
3133–3134.
18. Williams A, Hill SV, Thea S. J. Chem. Soc., Perkin. Trans. 2 1983;
437–446.
Acknowledgements
19. (a) Leffler JE. Science 1953; 117: 340; (b) Leffler JE, Grunwald E.
Rates and Equilibria of Organic Reactions. Wiley: New York,
1963.
20. Murdoch JR. J. Am. Chem. Soc. 1972; 94: 4415.
21. Shaik SS, Schlegel HB, Wolfe S. Theoretical Aspects of Physical
Organic Chemistry. Wiley: New York, 1992.
This work was written during the stay of E.H. at the
Institute of Fundamental Research of Organic Chemistry
at Kyushu University, as Visiting Professor. He thanks Dr
Shinjiro Kobayashi for the invitation.
22. (a) Marcus RA, Sutin N. J. Chem. Phys. 1956; 24: 966; (b) Haim
A, Sutin N. J. Am. Chem. Soc. 1966; 88: 434; (c) Cohen AO,
Marcus RA. J. Chem. Phys. 1968; 72: 4249; (d) Marcus RA. J.
Chem. Phys. 1968; 72: 891–899; (e) Kreevoy MM, Konasewich
DE. Adv. Chem. Phys. 1971; 21: 243; (f) Albery WJ. Rev. Phys.
Chem. 1980; 31: 227–263; (g) Pellerite MJ, Brauman JI. J. Am.
Chem. Soc. 1980; 102: 5993; (h) Murdoch JR. J. Am. Chem. Soc.
1983; 105: 2159–2164.
REFERENCES
1. Huxtable R. Biochemistry of Sulfur. Plenum Press: New York,
1986.
2. (a) Thorn GD, Ludwig RA. The Dithiocarbamates and Related
Compounds. Elsevier: Amsterdam, 1962; (b) Cremlyn RJ. In
Herbicides and Fungicides, McFarlane MR (ed). Special Publica-
23. Ritchie CD, Kubisty C, Ting GY. J. Am. Chem. Soc. 1983; 105:
279–284.
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 570–575