Structure-reactivity correlations in the aminolysis of aryl chloroformates

Article abstract of DOI:10.1002/kin.1022

The reactions of a series of secondary alicyclic amines with 4-methylphenyl and 4-methoxyphenyl chloroformates are subjected to a kinetic investigation in water, at 25.0°C, ionic strength 0.2 M (KCI). Under amine excess, pseudo-first-order rate coefficients (k_obs) are found for all reactions. Plots of k_obs vs [NH] (NH is the free amine) are linear, with the slope (k_N) pH independent, except the reactions of l-(2-hydroxyethyl)piperazine with both substrates at pH 6.2-7.3. The Broensted-type plots for the k_N values for the aminolysis of both chloroformates are linear, with slopes ca. 0.3, which is consistent with rate-determining formation of a zwitterionic tetrahedral intermediate (T±). With the PK_a and log k_N data for the present reactions, together with those for the same aminolysis of phenyl and 4-nitrophenyl chloroformates, two dual parametric equations are found for log k_N as a function of pK_a of the nucleophile, Hammett sigma of the "nonleaving" group, and pK_a of the "nonleaving" group, with coefficients β_N = 0.3, ρ_nlg = 0.7, and β_nlg = -0.2, respectively.

Full text of DOI:10.1002/kin.1022

Structure–Reactivity
Correlations in the
Aminolysis of Aryl
Chloroformates
´
´
ENRIQUE A. CASTRO,* MARIA G. RUIZ, JOSE G. SANTOS*
Facultad de Qu´ımica, Pontificia Universidad Cato´lica de Chile, Casilla 306, Santiago 22, Chile
Received 17 April 2000; accepted 16 November 2000
ABSTRACT: The reactions of a series of secondary alicyclic amines with 4-methylphenyl and
4-methoxyphenyl chloroformates are subjected to a kinetic investigation in water, at 25.0ЊC,
ionic strength 0.2 M (KCl). Under amine excess, pseudo-first-order rate coefficients (kobs) are
found for all reactions. Plots of kobs vs [NH] (NH is the free amine) are linear, with the slope
(kN) pH independent, except the reactions of 1-(2-hydroxyethyl)piperazine with both substrates
at pH 6.2–7.3. The Bro¨nsted-type plots for the kN values for the aminolysis of both chlorofor-
mates are linear, with slopes ca. 0.3, which is consistent with rate-determining formation of
a zwitterionic tetrahedral intermediate (TϮ). With the pKa and log kN data for the present
reactions, together with those for the same aminolysis of phenyl and 4-nitrophenyl chloro-
formates, two dual parametric equations are found for log kN as a function of pKa of the
nucleophile, Hammett sigma of the “nonleaving” group, and pKa of the “nonleaving” group,
with coefficients ␤N ϭ 0.3, ␳ ϭ 0.7, and ␤nlg ϭ Ϫ0.2, respectively. ᭧ 2001 John Wiley & Sons,
nlg
Inc. Int J Chem Kinet 33: 281–287, 2001
INTRODUCTION
constant ␳ (where X and Y are substituents on the
nucleophile and phenyl group of the substrate, respec-
tively) [14].
xy
Although the hydrolysis and solvolysis of alkyl and
aryl chloroformates have been extensively studied ki-
netically [1–9], less is known about the kinetics and
mechanism of the aminolysis of the above compounds
[10–16].
There have been some discrepancies regarding the
mechanism of the aminolysis of aryl chloroformates.
Lee and co-workers found a concerted mechanism in
the reactions of anilines with substituted phenyl chlo-
roformates in acetonitrile [14]. Their conclusion was
based mainly on a relatively large inverse secondary
kinetic isotope effect involving deuterated aniline nu-
cleophiles and a negative value of the cross-interaction
In contrast to the results above, Lee and co-workers
concluded that the pyridinolysis of substituted phenyl
chloroformates in acetonitrile is governed by a step-
wise mechanism, whereby the formation of a zwitter-
ionic addition tetrahedral intermediate is rate deter-
mining [15].
On the other hand, we have found that the reactions
of secondary alicyclic amines with phenyl and 4-ni-
trophenyl chloroformates in water are stepwise, with
rate-determining formation of a zwitterionic tetrahe-
dral intermediate [16].
In order to shed more light on the mechanism of
the aminolysis of aryl chloroformates and explain the
discrepancies above, in the present paper we report a
kinetic investigation of the reactions of secondary al-
Correspondence to: E. A. Castro (ecastro@puc.cl)
᭧ 2001 John Wiley & Sons, Inc.

282
CASTRO ET AL.
icyclic amines with 4-methylphenyl and 4-methoxy-
phenyl chloroformates (MeClF and MeOClF, respec-
tively) in water.
layer was dried with MgSO4, filtered under vacuum,
and the solvent removed. The crystallized products
showed the following mp: PiMeC 75.5–76.5ЊC,
MoMeC 86.0–87.0ЊC, PiMeOC 88.1–88.6ЊC, and
O
1
MoMeOC 69.6–70.0ЊC. The IR, H NMR, and 13C
NMR spectra were consistent with their structures.
O9C9Cl
X
O
MeCIF X ϭ CH3
MeOCIF X ϭ CH3O
O9C9N
Y
X
PiMeC
X ϭ Me, Y ϭ CH2
MoMeC X ϭ Me, Y ϭ O
PiMeOC X ϭ MeO, Y ϭ CH2
MoMeOC X ϭ MeO, Y ϭ O
EXPERIMENTAL
Materials
The substrates (MeClF and MeOClF) were from Al-
drich (97% and 98%, respectively) and used as pur-
chased. Amines were purified as described [17].
Kinetic Measurements
The reactions were followed by means of a Hewlett-
Packard 8453 diode array spectrophotometer, in water
at 25.0 Ϯ 0.1ЊC, ionic strength 0.2 M (KCl), and, in
some cases, in phosphate buffer 0.005 M.
Synthesis of Products
The O-4-methylphenyl carbamates of piperidine and
morpholine (PiMeC and MoMeC, respectively), and
the O-4-methoxyphenyl carbamates of piperidine and
morpholine (PiMeOC and MoMeOC, respectively)
were synthesized as follows. To a solution (10 mL) of
426 mg, 2.5 mmol, of MeClF (or 456 mg, 2.5 mmol,
of MeOClF) in acetonitrile, a solution (10 mL) of 425
mg (5 mmol) of piperidine (or 435 mg, 5 mmol, of
morpholine) in acetonitrile was added slowly. The
mixture was left 30 min at room temperature. Chlo-
roform (15 mL) was added to this mixture and the
solution washed with 10% aqueous HCl. The organic
The reactions were measured in the range 210–300
nm. The initial substrate concentration was 2–5 ϫ
Ϫ5
10 M. All reactions were studied under excess of
amine over the substrate (see below). Pseudo-first-or-
der rate coefficients (kobs) were found for all reactions.
The experimental conditions and kobs values for these
reactions are shown in Tables I and II.
Product Studies
For the reactions of both substrates with piperidine and
morpholine, one of the products was identified as the
Table I Experimental Conditions and kobs Values for the Aminolysis of 4-Methylphenyl Chloroformate (MeClF)a
No. of
Runs
Ϫ1
Amine
pH
104 [N]tot,b M
102 kobs, s
piperidinec
6.2
6.5
6.2
6.5
6.8
7.0
7.3
6.2
6.5
7.0
4.2
4.5
10–50
10–50
0.150–0.272
0.148–0.394
1.40–5.75
1.45–2.81
1.75–3.05
2.04–3.60
1.96–3.60
1.32–2.13
1.36–2.49
1.79–3.76
1.15–1.52
1.21–1.95
4
4
9
4
4
4
4
6
6
5
6
6
1-(2-hydroxyethyl)piperazinec
1.0–12.0
2.0–5.0
2.0–5.0
2.0–5.0
2.0–5.0
2.0–9.0
1.5–7.0
2.0–5.0
2.0–7.0
2.0–7.0
morpholinec
1-(2-hydroxyethyl)piperazinium
a In aqueous solution at 25.0ЊC, ionic strength 0.2 M (KCl).
b Concentration of total amine (free base plus protonated forms).
Ϫ
c In the presence of 5 ϫ 10 3 M phosphate buffer.

STRUCTURE–REACTIVITY CORRELATIONS IN THE AMINOLYSIS OF ARYL CHLOROFORMATES
283
Table II Experimental Conditions and kobs Values for the Aminolysis of 4-Methoxyphenyl Chloroformate (MeOClF)a
No. of
Runs
Ϫ1
Amine
pH
104 [N]tot,b M
102 kobs, s
piperidinec
6.0
6.2
6.5
6.2
6.5
7.0
7.3
6.0
6.2
6.5
4.5
4.8
10–40
10–50
10–50
0.154–0.285
0.162–0.383
0.197–0.525
1.54–5.93
1.63–3.39
1.97–3.76
2.10–4.27
1.43–2.12
1.43–2.11
1.61–2.68
1.27–2.28
1.32–2.54
3
4
3
8
5
4
4
6
4
6
6
5
1-(2-hydroxyethyl)piperazinec
1.0–12.0
1.0–5.0
2.0–5.0
2.0–5.0
2.0–12.0
2.0–7.0
1.5–6.0
2.0–7.0
2.0–6.0
morpholinec
1-(2-hydroxyethyl)piperazinium
a In aqueous solution at 25.0ЊC, ionic strength 0.2 M (KCl).
b Concentration of total amine (free base plus protonated forms).
Ϫ
c In the presence of 5 ϫ 10 3 M phosphate buffer.
corresponding carbamate, by comparison of the UV
spectra at the end of the reactions with that of an au-
thentic sample of the corresponding carbamate under
the same experimental conditions.
and kN are the rate constants for hydrolysis and ami-
nolysis of the substrates, respectively, and NH repre-
sents a secondary alicyclic amine free base.
d[P]
ϭ kobs [ArOCOCl]
(1)
(2)
dt
RESULTS AND DISCUSSION
kobs ϭ ko ϩ kN [NH]
The general rate law obtained in the present reactions
is given by Eqs. (1) and (2), where P is the carbamate
product, Ar is 4-methylphenyl or 4-methoxyphenyl, ko
The second-order rate coefficients for aminolysis
(kN) were obtained as the slopes of plots of Eq. (2) at
constant pH, the slopes being pH independent in the
reactions of piperidine, morpholine, and 1-(2-hy-
droxyethyl)piperazinium ion. In contrast, in the reac-
tions of 1-(2-hydroxyethyl)piperazine in the pH range
6.2–7.3, the slopes were dependent on the pH values
employed. This presumably is due to the existence of
two nucleophiles (species 1 and 2 in Scheme I) which
can react with the substrates, as found in the reactions
of this amine with similar substrates [16,18]. In this
case, the reaction law obtained is given by Eq. (3),
where kN1 and kN2 are the second-order rate constants
for the reactions of 1 and 2, respectively, F1 and F2 are
the corresponding molar fractions, and [NH]tot is the
concentration of total amine (the sum of structures 1–
4 in Scheme I) [18]. The F1 and F2 values can be
determined from the pKa values of structures 2, 3, and
4 [18].
kobs ϭ ko ϩ (kN1F1 ϩ kN2F2) [NH]tot
(3)
Scheme I
The slopes of the linear plots of kobs vs [NH]tot at

284
CASTRO ET AL.
Table III Values of the pKa of the Conjugate Acids of Secondary Alicyclic Amines and kN for the Aminolysis of
4-Methylphenyl Chloroformate (MeClF) and 4-Methoxyphenyl Chloroformate (MeOClF)a
Ϫ
4
Ϫ
Ϫ1
10 kN, s 1 M
Amine
pKa
MeCIF
MeOClF
piperidine
1-(2-hydroxyethyl)piperazine
morpholine
11.24
9.38
8.78
5.90
3.2 Ϯ 0.2
4.7 Ϯ 0.2
0.34 Ϯ 0.20b
0.35 Ϯ 0.04
0.08 Ϯ 0.05b
0.04 Ϯ 0.01c
0.30 Ϯ 0.09b
0.42 Ϯ 0.08
0.09 Ϯ 0.04b
0.05 Ϯ 0.01d
1-(2-hydroxyethyl)piperazinium
a Values of both pKa and kN in aqueous solution, at 25.0ЊC, ionic strength 0.2 M (KCl). Errors shown for kN are standard deviations.
b Values determined at pH 6.2–7.3 by means of Eqs. (3–5).
c Value determined at pH 4.2 and 4.5 by means of Eq. (2).
d Value determined at pH 4.5 and 4.8 by means of Eq. (2).
Ϯ
constant pH correspond to kNobs of Eq. (4). Rearrange-
ment of this equation yields Eq. (5). The kN1 and kN2
values were obtained as the slope and intercept, re-
spectively, of linear plots of kNobs/F2 vs F1/F2 [18].
These values, together with those of kN for the other
amines, are shown in Table III.
onic tetrahedral intermediate (T ) is the rate-determin-
ing step [10–13,15,17–21]. In contrast, the concerted
aminolysis of similar compounds shows values of ␤N
in the region 0.5–0.6 [22].
Although the ␤N values obtained in this workare
consistent with a stepwise mechanism with rate-deter-
mining formation of T , the concerted process cannot
Ϯ
be rigorously excluded. Nevertheless, we believe that
the stepwise mechanism is more likely considering: (i)
the magnitude of the ␤N values and (ii) the fact that
the same aminolysis of 4-nitrophenyl chloroformate is
stepwise [16]. In this case, the T formed should be
more unstable than that in the present reactions, in
k
Nobs ϭ kN2F2 ϩ kN1F1
(4)
(5)
kNobs/F2 ϭ kN2 ϩ kN1 F1/F2
Ϯ
The hydrolysis rate constant (ko) was found as the
intercept of a plot of Eq. (2). For the reactions of
MeClF and MeOClF, these values are 0.01 s and
Ϫ
1
Ϫ
1
0.012 s , respectively, at the pH range studied (4.2–
7.3). The hydrolysis reactions were also measured in
the absence of amine, and the ko values obtained were
similar to those found in the aminolysis. In some re-
actions, the contribution of the ko term in Eq. (2) to
the total rate constant observed was more important
than the aminolysis term, kN[NH].
Some of the reactions were studied with only a
small excess of total amine over the substrate, but be-
cause of the fact that the simultaneous hydrolysis re-
action tookplace, the pseudo-first-order condition was
preserved, as indicated by the good correlation coef-
ficients obtained (greater than 0.999).
The kN values, together with the pKa values of the
conjugate acids of the amines, are given in Table III,
and the Bro¨nsted-type plots obtained with these data
are shown in Figure 1. The values of the slopes of the
lines (␤N) are 0.3 for the aminolysis of both substrates.
The magnitude of ␤N is in agreement with the val-
ues of the Bro¨nsted slopes found in the stepwise mech-
anism of the aminolysis of phenyl and 4-nitrophenyl
chloroformates [16] and also in accord with those of
similar reactions when the formation of the zwitteri-
Figure 1 Bro¨nsted-type plots obtained in the aminolysis
of 4-methylphenyl (MeClF) and 4-methoxyphenyl (Me-
OClF) chloroformates in water, 25.0ЊC, ionic strength 0.2 M
(KCl). The value of both slopes is 0.3.

STRUCTURE–REACTIVITY CORRELATIONS IN THE AMINOLYSIS OF ARYL CHLOROFORMATES
285
view of the two good nucleofuges involved in the for-
Ϯ
mer T .
According to the kinetic results, the analysis of
products, and the Bro¨nsted plots, the mechanism
shown in Scheme II (X ϭ CH3 or CH3O) is proposed
for the reactions under scrutiny. The steady-state treat-
Ϯ
ment to the tetrahedral intermediate T gives kN ϭ k1 k2/
(kϪ ϩ k2 ). According to our results, the first step is
1
limiting; therefore, it follows that in this scheme,
k2 ϾϾ kϪ , and therefore, kN ϭ k1.
1
With the kN values found in the present reactions
and those obtained in the same aminolysis of phenyl
and 4-nitrophenyl chloroformates, together with the
pKa values for the amines and the ␴ values of aryl
substituents (see Table IV), Eq. (6) can be deduced by
dual regression analysis (n ϭ 21 , R2 ϭ 0.92). In this
expression NH refers to a secondary alicyclic amine
and nlg to the “nonleaving” or acyl group of the sub-
strate. The pKa(NH) values have been statistically cor-
rected, with p ϭ 2 for all aminium ions, except piper-
azinium dication with p ϭ 4 [17,24]. The coefficients
for pKa and ␴ (␤N ϭ 0.3 and ␳nlg ϭ 0.7, respectively)
are subjected to an error of Ϯ0.1.
Figure 2 Logarithmic kN plot of the experimental vs the
calculated values, through Eq. (6), for the aminolysis of X-
4-phenyl chloroformates in water, 25.0ЊC, ionic strength 0.2
M (KCl).
0.92). The calculated log kN values, through Eq. (7),
are shown in Table IV. A logarithmic plot (not shown)
of the experimental vs calculated kN is linear with unity
slope.
log kN ϭ 1.2 ϩ 0.3[pKa(NH) ϩ log p] ϩ 0.7 ␴(nlg)
(6)
A logarithmic plot of the experimental kN values vs
the calculated ones (values shown in Table IV)
through Eq. (6) can be seen in Figure 2; the slope is
unity.
Another multiparametric equation (Eq. (7)) can be
deduced as a function of the basicity of both the nu-
cleophile and the “nonleaving” group (n ϭ 21, R2 ϭ
log kN ϭ 3.2 ϩ 0.3[pKa(NH)
ϩ log p] Ϫ 0.2 pKa(nlg)
(7)
The sensitivity of kN to the amine and nonleaving
group basicity are in agreement with those exhibited
in the aminolysis of aryl esters and diaryl carbonates
when the formation of the tetrahedral intermediate
Ϯ
(T ) is the rate-determining step [20,21]. The value of
the coefficient for the substituent in the nonleaving
group (␳ ϭ 0.7) is a little larger than that obtained
nlg
in the pyridinolysis of the same compounds in 90%
aqueous dioxane (␳ ϭ 0.5) [10], and a little lower
nlg
than those found in the pyridinolysis of the same sub-
strates in acetonitrile (␳nlg ca. 1) [15]. These ␳nlg values
are also consistent with a stepwise mechanism where
Ϯ
formation of T is rate-determining for these reactions.
The fact that the reactions of secondary alicyclic
amines (saa) with substituted phenyl chloroformates
in water are stepwise, with rate-limiting formation of
Ϯ
the zwitterionic tetrahedral intermediate (T ), seems
to be in conflict with the concerted mechanism found
in the reactions of anilines with phenyl chloroformates
in acetonitrile [14]. The concertedness of the latter re-
Scheme II

286
CASTRO ET AL.
Table IV Values of t pKa (Statistically Corrected) and log kN for the Aminolysis of 4-X-Phenyl Chloroformates in
Water, 25.0ЊC, Ionic Strength 0.2 M (KCl)
Ϫ
Ϫ1
log (kN/s 1 M )
Amine
pKa ϩ log p
expl
Calc. (Eq. 6)
Calc. (Eq. 7)
X ϭ MeOa
4.29
piperidine
1-(2-hydroxyethyl)piperazine
morpholine
11.54
9.68
9.08
6.20
6.20
4.67
3.48
3.63
2.95
2.65
4.35
3.82
3.63
2.83
2.83
3.76
3.57
2.77
2.77
X ϭ Meb
4.36
3.83
3.64
2.84
2.84
X ϭ Hc
4.48
3.95
3.75
2.95
1-(2-hydroxyethyl)piperazinium
piperidine
1-(2-hydroxyethyl)piperazine
morpholine
11.54
9.68
9.08
6.20
6.20
4.51
3.53
3.54
2.90
2.60
4.37
3.84
3.65
2.85
2.85
1-(2-hydroxyethyl)piperazinium
piperidine
1-(2-hydroxyethyl)piperazine
morpholine
11.54
9.68
9.08
6.20
6.20
4.42
3.94
3.89
3.16
3.11
4.41
3.89
3.70
2.89
2.89
1-(2-hydroxyethyl)piperazinium
2.95
X ϭ NO2
d
piperidine
1-(2-hydroxyethyl)piperazine
morpholine
piperazinium ion
1-(2-hydroxyethyl)piperazinium
11.54
9.68
9.08
6.41
6.20
6.20
4.95
4.43
4.22
3.43
3.56
3.63
5.01
4.48
4.29
3.55
3.49
3.49
5.00
4.48
4.29
3.54
3.48
3.48
a
␴
ϭ Ϫ0.27, pKa (nlg) ϭ 10.2.
ϭ Ϫ0.17, pKa (nlg) ϭ 10.1.
ϭ 0, pKa (nlg) ϭ 9.9.
X
b
c
d
␴
␴
X
X
␴
ϭ 0.79, pKa (nlg) ϭ 7.1.
X
Ϯ
actions was deduced from a relatively large inverse
secondary kinetic isotope effect involving deuterated
aniline nucleophiles, a small negative value of the
cross-interaction constant, ␳XY (where X and Y are the
substituents on the aniline and the phenoxy group, or
“nonleaving” group of the substrate, respectively) and
a value of ca. 0.8 for ␤X [14].
breakdown of T to products, which usually exhibits
values of ␤N ϭ ␤X ϭ 0.8 Ϫ1.0 [10–13,17–21]. This
could be due to the faster expulsion of anilines from
Ϯ
T than isobasic pyridines [25,26], which could en-
force a change in the rate-limiting step, from formation
of T for the pyridinolysis, to breakdown of T to
products for the anilinolysis.
Ϯ
Ϯ
The above conclusion was later reconsidered in the
light of the results obtained in the pyridinolysis of
phenyl chloroformates in acetonitrile [15]. For these
reactions, a value of ␤X ϭ 0.3 was found, which was
interpreted through a stepwise mechanism with rate-
Since the pyridinolysis of phenyl chloroformates in
acetonitrile proceeds with rate-determining formation
of the tetrahedral intermediate, it seems at first sight
surprising that the same is true for the reactions of saa
with the same substrates in water (this work). This is
because it is known that saa are much better nucleo-
Ϯ
determining formation of an intermediate T on the
Ϯ
reaction path [15]. It was reasoned that the reactions
of anilines with these substrates in the same solvent
fuges from T than isobasic pyridines [18,25,26] and
could enforce a change in the rate-limiting step from
Ϯ
Ϯ
Ϯ
should also be stepwise with formation of T as the
T formation to breakdown of T to products. Nev-
ertheless, it should be taken into account that the
change of solvent from acetonitrile to water should
rate-limiting step [15]. It seems to us that the magni-
tude of ␤X (ca. 0.8) is not consistent with rate-deter-
Ϯ
Ϯ
mining formation of T , but rather with rate-limiting
decrease the rate of expulsion of saa from T , com-

STRUCTURE–REACTIVITY CORRELATIONS IN THE AMINOLYSIS OF ARYL CHLOROFORMATES
287
5. Kevill, D. N.; D’Souza, M. J. J Chem Soc, Perkin Trans
2 1997, 1721.
6. Kevill, D. N.; Bond, M. W.; D’Souza, M. J. J Org Chem
1997, 62, 7869.
7. Kevill, D. N.; D’Souza, M. J. J Org Chem 1998, 63,
2120.
8. Kevill, D. N.; Kim, J. C.; Kyong, J. B. J Chem Res (S)
1999, 150.
9. Possidonio, S.; Siviero, F.; El Seoud, O. A. J Phys Org
Chem 1999, 12, 325.
10. Butler, A. R.; Robertson, I. H.; Bacaloglu, R. J Chem
Soc, Perkin Trans 2 1974, 1733.
11. Castro, E. A.; Moodie, R. B. J Chem Soc, Perkin Trans
2 1974, 658.
12. Bond, P. M.; Castro, E. A.; Moodie, R. B. J Chem Soc,
Perkin Trans 2 1976, 68.
13. Castro, E. A.; Ureta, C. J Chem Res (S) 1987, 358.
14. Yew, K. H.; Koh, H. J.; Lee, H. W.; Lee, I. J Chem Soc,
Perkin Trans 2 1995, 2263.
15. Koh, H. J.; Han, K. L.; Lee, H. W.; Lee, I. J Org Chem
1998, 63, 9834.
16. Castro, E. A.; Ruiz, M. G.; Salinas, S.; Santos, J. G. J
Org Chem 1999, 64, 4817.
17. Castro, E. A.; Ureta, C. J Org Chem 1989, 54, 2153.
18. Castro, E. A.; Ureta, C. J Chem Soc, Perkin Trans 2
1991, 63.
19. Palling, D. J.; Jencks, W. P. J Am Chem Soc 1984, 106,
4869.
20. Satterthwait, A. C.; Jencks, W. P. J Am Chem Soc 1974,
96, 7018.
21. Gresser, M. J.; Jencks, W. P. J Am Chem Soc 1977, 99,
6963, 6970.
pensating, therefore, its superior intrinsic nucleofu-
gality. The lower nucleofugality rate from T of a
Ϯ
given amine in a very polar solvent, compared to a
Ϯ
less polar one, is due to the ionic nature of T (highly
polar), relative to the lower polarity of the transition
Ϯ
state for T formation [21].
The reactions of saa with phenyl and 4-nitrophenyl
chlorothionoformates in water were found to be gov-
erned by a stepwise mechanism, with rate-determining
Ϯ
formation of a tetrahedral intermediate T [27]. This
conclusion was based on the magnitude of the value
of ␤N ϭ 0.26 [27]. This means that substitution of
carbonyl by thiocarbonyl in the substrate does not
change either the mechanism or the rate-determining
step of the aminolysis of the above compounds.
On the other hand, it has been found that the change
of CS by CO as the electrophilic group of the substrate
Ϯ
destabilizes kinetically the intermediate T by increas-
ing the nucleofugality from this species of both the
amine and leaving group of the substrate [28]. This
Ϫ
Ϯ
has been attributed to the greater ability of O in T ,
Ϫ
relative to S , in forming a double bond and expelling
a given nucleofuge [28,29]. Therefore, the results
above mean that the greater nucleofugality rate
Ϫ
Ϫ
Ϯ
brought about by the change of S to O in T is not
enough to provoke a change in the rate-determining
Ϯ
step or to bring such instability to T as to shift the
mechanism from stepwise to concerted.
22. Castro, E. A.; Iban˜ez, F.; Salas M.; Santos, J. G. J Org
Chem 1991, 56, 4819.
23. Castro, E. A.; Salas M.; Santos, J. G. J Org Chem 1994,
59, 30.
We thankFONDECYT of Chile (project 1960460) for fi-
nancial assistance to this work.
24. Bell, R. P. The Proton in Chemistry; Methuen: London,
1959; p 159.
25. Castro, E. A.; Iban˜ez, F.; Saitua A. M.; Santos, J. G. J
Chem Res (S) 1993, 56.
BIBLIOGRAPHY
26. Castro, E. A.; Leandro, L.; Milla´n, P.; Santos, J. G. J
Org Chem 1999, 64, 1953.
27. Castro, E. A.; Cubillos, M.; Santos, J. G. J Org Chem
1997, 62, 4395.
28. Castro, E. A.; Iban˜ez, F.; Santos, J. G.; Ureta, C. J
Chem.Soc, Perkin Trans 2 1991, 1919.
29. Hill, S. V.; Thea, S.; Williams, A. J Chem Soc, Perkin
Trans 2 1983, 437.
1. Kevill, D. N. The Chemistry of Acyl Halides; Patai, S.,
Ed.; Interscience: London, 1972; p 381.
2. Kevill, D. N.; Kyong, J. B. J Org Chem 1992, 57, 258.
3. Koo, I. S.; Yang, K.; Kang, K.; Oh, H. K.; Lee, I. Bull
Korean Chem Soc 1996, 17, 520.
4. Koo, I. S.; Yang, K.; Koo, J. C.; Park, J.-K.; Lee, I. Bull
Korean Chem Soc 1997, 18, 1017.