Kinetics and mechanism of the reactions of aryl chlorodithioformates with pyridines and secondary alicyclic amines

Article abstract of DOI:10.1002/poc.1555

The reactions of pyridines and secondary alicyclic (SA) amines with phenyl and 4-nitrophenyl chlorodithioformates (PClDTF and NPClDTF, respectively) are subjected to a kinetic study in aqueous ethanol (44 wt% ethanol) solution, at 25.0 ° C, and an ionic s

Full text of DOI:10.1002/poc.1555

Research Article
Received: 19 December 2008,
Revised: 5 March 2009,
Accepted: 5 March 2009,
Published online in Wiley InterScience: 28 April 2009
(www.interscience.wiley.com) DOI 10.1002/poc.1555
Kinetics and mechanism of the reactions of
aryl chlorodithioformates with pyridines and
secondary alicyclic amines
a
a
a
*
´
Enrique A. Castro , Marcela Gazitu´a and Jose G. Santos
The reactions of pyridines and secondary alicyclic (SA) amines with phenyl and 4-nitrophenyl chlorodithioformates
(PClDTF and NPClDTF, respectively) are subjected to a kinetic study in aqueous ethanol (44 wt% ethanol) solution, at
25.0 -C, and an ionic strength of 0.2 M (KCl). The reactions are studied spectrophotometrically. Under amine excess,
pseudo-first-order rate coefficients (kobs) are found. Plots of kobs versus [amine] are linear and pH independent, with
slope kN. The Brønsted-type plots (log kN vs. pKa of aminium ions) are linear for the reactions of PClDTF with SA amines
(slope b of 0.3) and pyridines (b ¼ 0.26) and those of NPClDTF with pyridines (b ¼ 0.30). For the reaction of NPClDTF
with SA amines the Brønsted-type plot is biphasic, with slopes b1 ¼ 0.2 (at high pKa) and b2 ¼ 1.1 (at low pKa). The pKa
value at the center of curvature (pK0a) is 7.7. The magnitude of the slopes indicates that the mechanisms of these
reactions are stepwise, with the formation of a zwitterionic tetrahedral intermediate as the rate-determining step,
except for the reaction of NPClDTF with SA amines where there is a change in the rate-determining step, from
formation to breakdown of the tetrahedral intermediate, as the amine basicity decreases. Copyright ß 2009 John
Wiley & Sons, Ltd.
Keywords: kinetics; mechanism; aminolysis; aryl chlorodithioformates; Brønsted plot; tetrahedral intermediates
pyridines and SA amines with phenyl and 4-nitrophenyl
INTRODUCTION
chlorodithioformates (PClDTF and NPClDTF, respectively, Scheme 1).
Specific objectives are (i) to assess the effect of the nonleaving
group on the kinetics and mechanism, by comparing the
reactions of PClDTF and NPClDTF with a given amine series; (ii) to
analyze the influence of the sulfur atoms in aryl chlorodithio-
formates, by comparison of the present reactions with the same
aminolyses of the corresponding thiono derivatives (PClTF and
NPClTF, respectively, Scheme 1) and aryl chloroformates (PClF and
NPClF, respectively, Scheme 1). It is of special interest to see
whether there is a change of mechanism by the substitution of an
The solvolysis reactions of aryl chloroformates (ArO—
CO—Cl),[1–3] phenyl chlorothiolformate (PhS—CO—Cl),[4,5] phe-
nyl chlorothionoformate (PhO—CS—Cl),[6–8] and phenyl chlor-
odithioformate (PhS—CS—Cl)[8–10] have been studied kinetically
and their mechanisms clearly established. By comparison of the
solvolysis of phenyl chloroformate with those of the correspond-
ing thiol and dithio analogues, it was concluded that the
substitution of the oxygen atoms in phenyl chloroformate by
sulfur atoms (to give the corresponding thiol and dithio
chloroformates, respectively) gradually changes the mechanism
from addition–elimination, for the chloroformate, to an SN1
ionization process for phenyl chlorodithioformate.[8]
On the other hand, the reactions of aryl chloroformates with
secondary alicyclic (SA) amines[11,12] and quinuclidines,[13] and
those of aryl chlorothionoformates with pyridines,[14] SA
amines[15] and quinuclidines[16] show stepwise mechanisms with
the formation of a zwitterionic tetrahedral intermediate as the
rate-limiting step. The rate-determining step has been suggested
to change at pK0a (pKa at the center of the Brønsted curvature),
thereby indicating that the pK0a value is governed by the basicity
of the amine, solvent effects, the nucleophile–nucleofuge
interaction, and the nucleofugality of the leaving group.[17–21]
However, the effect of the nonleaving-group on the reaction
mechanism is not yet completely understood. It has been found
that the pK0a value increases as the substituent in the nonleaving
group increases its electron-withdrawing ability,[22] this argument
being in agreement with the results reported by Gresser and
Jencks.[23]
Scheme 1.
*
Correspondence to: J. G. Santos, Facultad de Qu´ımica, Pontificia Universidad
´
Catolica de Chile, Casilla 306, Santiago 6094411, Chile.
E-mail: jgsantos@uc.cl
To extend our kinetic studies on the aminolysis of chlorothio-
formates and with the aim to shed some light on these
mechanisms, in the present work we investigate the reactions of
a
E. A. Castro, M. Gazitu´a, J. G. Santos
Facultad de Qu´ımica, Pontificia Universidad Catolica de Chile, Casilla 306,
Santiago 6094411, Chile
´
J. Phys. Org. Chem. 2009, 22 1030–1037
Copyright ß 2009 John Wiley & Sons, Ltd.

REACTIONS OF ARYL CHLORODITHIOFORMATES
O-aryl group by S-aryl in the reactant structure; (iii) to assess the
influence of the amine nature on the kinetics and mechanisms of
these reactions. This will be achieved by a kinetic comparison of
the reactions of the title substrates with both amine series.
The reactions of PClDTF with piperazine and piperazinium ion
were studied at pH values ranged over 6.5–7.5, where mixtures of
bothaminesarepresent.Inthesecases,thekN valueswereobtained
through Eqns (3) and (4).[24] In these equations kN,obs is a global
nucleophilic rate constant (corresponding to the mixture of
nucleophiles), [N]tot is the total piperazine (piperazineþ
piperaziniumion) concentration, FN and FNH arethe molar fractions
ofpiperazineandpiperaziniumion, respectively, andkN andkNH are
theircorrespondingnucleophilicrateconstants.ThevaluesofkN obs
were obtained as the slopes of linear plots of kobs versus [N]tot at
constant pH. The nucleophilic rate constants for the reactions of
PClDTF with piperazine (kN) and piperazinium ion (kNH) were
determined through Eqn (4), as described in Reference [24].
RESULTS AND DISCUSSION
The kinetic law obtained under the reaction conditions is that
described by Eqn (1), where P is the corresponding dithiocarba-
mate product, S the substrate, and kobs is the pseudo-first-order
rate coefficient (excess of amine was used throughout). The
experimental conditions of the reactions and the kobs values
obtained are shown in Tables 1–4.
kobs ¼ k0 þ kNobs½Nꢀtot
kNobs ¼ FN kN þ FNH kNH
(3)
(4)
d½Pꢀ
¼ kobs½Sꢀ
(1)
dt
The k0 values obtained for the reactions of PClDTF in this study
(with both SAA and pyridines) ranged from 0.01 to 0.02 sꢁ1. These
values are in the expected order of magnitude based on the work
of Kevill and D’Souza[8] on the solvolysis reactions of PDTClF in
ethanol and in 60–90% ethanol aqueous solutions. For instance,
Plots of kobs against [amine] at constant pH were linear in
accordance with Eqn (2), where k0 and kN are the rate coefficients
for solvolysis and aminolyses (SA amines and pyridines) of the
substrates, respectively. The values of k0 and kN were pH
independent.
the k0 values at 70 and 60% ethanol are 0.0018 and 0.007 sꢁ1
,
respectively. This shows that k0 increases with the increase of
water content in the solvent mixture.
kobs ¼ k0 þ kN½amineꢀ
(2)
Table 1. Experimental conditions and kobs values for the reactions of secondary alicyclic (SA) amines with phenyl chlorodithio-
formate (PClDTF)a
b
SA amine
Piperidine
pH
FN
103 [N]tot (M)c
103 kobs (sꢁ1
)
No. of runs
10.52
10.82
11.12
6.5d
0.33
0.50
0.67
e
0.510–5.10
0.500–5.00
0.510–5.10
2.00–5.00
0.500–5.00
0.500–5.00
2.75–5.00
2.00–5.00
1.25–5.00
0.250–2.50
0.500–5.00
0.500–5.00
1.28–5.10
1.38–2.50
0.613–5.21
0.500–4.92
0.500–5.00
0.500–4.25
2.89–5.26
1.25–5.00
55.7–131
30.5–207
72.0–335
21.4–27.9
16.1–25.0
21.2–33.8
30.8–34.9
31.9–45.8
40.0–121
15.8–109
53.4–245
25.3–73.5
35.0–76.6
38.8–45.1
32.3–97.9
37.1–111
18.5–33.0
17.8–37.4
38.1–56.5
112–170
6
6
7
5
6
6
4
5
6
6
7
6
6
4
8
6
6
6
4
5
Piperazine
6.8d
f
g
h
i
7.0d
7.2d
7.5d
9.41
9.71
10.01
9.09
9.39
8.08
8.48
9.78
7.33
7.63
7.93
5.37
0.33
0.50
0.67
0.50
0.67
0.294
0.50
0.67
0.33
0.50
0.67
0.50
1-(2-Hydroxyethyl)piperazine
Morpholine
Formylpiperazine
Piperazinium ion
a In 44 wt% ethanol–water, at 25 8C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
d 0.005 M phosphate buffer.
e Free piperazine and piperazinium ion fractions were 0.0005737 and 0.93045, respectively.
f Free piperazine and piperazinium ion fractions were 0.001185 and 0.96303, respectively.
g Free piperazine and piperazinium ion fractions were 0.0019015 and 0.97524, respectively.
h Free piperazine and piperazinium ion fractions were 0.003036 and 0.98243, respectively.
i Free piperazine and piperazinium ion fractions were 0.005083 and 0.98660, respectively.
J. Phys. Org. Chem. 2009, 22 1030–1037
Copyright ß 2009 John Wiley & Sons, Ltd.
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E. A. CASTRO, M. GAZITUA AND J. G. SANTOS
Table 2. Experimental conditions and kobs values for the reactions of secondary alicyclic (SA) amines with 4-nitrophenyl
chlorodithioformate (NPClDTF)a
b
SA amine
Piperidine
pH
FN
103 [N]tot(M)c
103 kobs (sꢁ1
)
No. of runs
8.5d
9.0d
9.5d
9.4
9.7
8.5
0.00476
0.0149
0.0457
0.33
0.500–3.50
0.500–4.25
0.500–2.75
0.500–5.00
0.500–0.425
0.500–5.00
0.500–5.00
0.500–5.00
0.500–5.00
0.500–5.00
0.500–5.00
0.500–5.00
0.500–5.00
0.500–5.00
10.4–104
3.64–8.28
4.51–17.8
8.75–38.0
38.3–328
75.9–522
20.7–101
27.6–101
31.2–289
3.75–10.9
4.00–22.5
9.32–56.4
5.24–43.2
11.8–75.6
12.7–105
3.50–17.5
4.88–29.9
5.13–38.7
5
6
4
6
6
7
7
7
7
7
7
7
7
7
7
7
7
Piperazine
0.50
1-(2-Hydroxyethyl)piperazine
0.205
0.448
0.720
0.0104
0.0321
0.0948
0.33
9.0
9.5
Morpholine
6.5e
7.0e
7.5e
7.33
7.63
7.93
5.07
5.37
5.67
Formylpiperazine
Piperazinium ion
0.50
0.67
0.33
0.50
10.4–104
10.4–104
0.67
a In 44 wt% ethanol–water, at 25 8C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
d 0.005 M borate buffer.
e 0.005 M phosphate buffer.
Table 3. Experimental conditions and kobs values for the reactions of pyridines with phenyl chlorodithioformate (PClDTF)a
b
Pyridine substituent
3,4-Diamino
pH
FN
103 [N]tot (M)c
103 kobs (sꢁ1
)
No. of runs
9.15
9.45
9.75
8.84
9.14
9.44
8.5
9.0
9.5
6.6
6.9
0.33
0.50
0.67
0.33
0.50
0.67
0.25
0.51
0.77
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.67
0.33
0.50
0.67
0.50
0.67
3.25–32.5
3.35–33.5
3.13–31.3
5.01–50.1
4.91–68.7
3.70–37.0
4.60–18.4
1.84–18.4
1.06–10.6
10.0–25.0
2.48–24.8
2.32–23.2
5.03–50.3
5.14–51.4
4.78–47.8
7.32–73.2
12.2–48.9
42.3–89.8
10.1–101
25.8–103
25.5–102
10.3–103
24.6–138
25.7–177
31.8–236
28.7–181
31.6–352
53.6–237
22.1–60.0
14.9–82.6
21.4–77.7
21.6–40.0
12.7–48.5
16.3–55.4
19.2–61.1
18.8–66.3
25.7–90.3
27.3–48.3
27.8–54.1
13.3–16.2
9.33–16.7
8.50–16.7
12.2–15.6
14.3–21.1
7
7
7
7
6
7
6
7
7
4
7
7
7
7
7
6
6
4
7
6
6
6
4-Dimethylamino
4-Amino
4-Amino-3-bromo
3,4-Dimethyl
7.2
5.38
5.68
5.98
4.33
4.93
2.37
2.67
2.97
2.17
2.47
None
3-Carbamoyl
3-Chloro
a In 44 wt% ethanol–water, at 25 8C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
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REACTIONS OF ARYL CHLORODITHIOFORMATES
Table 4. Experimental conditions and kobs values for the reactions of pyridines with 4-nitrophenyl chlorodithioformate (NPClDTF)a
b
Pyridine substituent
4-Oxy
pH
FN
103 [N]tot (M)c
103 kobs (sꢁ1
)
No. of runs
8.5d
9.0d
9.5d
9.05
9.45
9.75
9.14
9.44
8.60
8.90
9.10
6.60
6.90
7.20
5.38
5.68
5.98
4.33
4.63
4.93
3.13
3.43
3.73
4.00
1.89
2.17
2.47
0.000315
0.001
0.0099
0.285
0.50
12.7–50.8
5.02–50.2
4.84–48.4
0.541–5.41
0.491–4.91
0.541–5.41
0.501–5.01
0.524–5.24
0.671–6.71
0.693–6.93
0.516–5.16
0.679–6.79
0.674–4.72
0.670–3.69
0.526–2.89
0.526–4.47
0.543–54.3
6.07–60.7
4.88–48.8
4.89–41.6
5.34–53.4
5.05–50.5
5.41–54.1
13.3–53.4
10.4–104
2.84–10.3
4.37–20.9
5.50–43.6
9.40–62.0
11.2–93.3
15.5–125
13.4–62.7
15.9–94.8
16.8–75.6
30.1–123
16.6–158
4.55–27.8
5.73–26.4
6.14–24.6
4.78–9.30
5.86–10.9
4.18–17.5
6.20–24.6
7.89–28.0
9.14–25.3
2.39–10.7
3.14–11.1
3.18–12.4
3.80–13.6
1.90–7.13
1.28–9.40
2.06–11.2
6
7
7
7
7
7
7
6
6
7
7
4
5
4
4
6
7
7
7
5
7
7
7
6
5
7
7
3,4-Diamino
0.67
0.50
0.67
4-Dimethylamino
4-Amino
0.294
0.454
0.60
4-Amino-3-bromo
3,4-Dimethyl
None
0.33
0.50
0.67
0.33
0.50
0.67
0.33
0.50
0.67
0.74
0.85
0.92
3-Carbamoyl
0.955
0.33
0.50
3-Chloro
10.2–102
10.3–103
0.67
a In 44 wt% ethanol–water, at 25 8C, ionic strength 0.2 M (KCl).
b Free amine fraction.
c Concentration of total amine (free base plus protonated forms).
d 0.005 M borate buffer.
For the reactions of PClDTF and NPClDTF with SA amines the
values of kN, obtained as the slopes of plots of Eqns (2) or (4), and
the pKa of the conjugate acids of the amines are summarized in
Table 5. Similar values for the reactions of these substrates with
pyridines are shown in Table 6.
Figures 1 and 2 show the Brønsted-type plots for the reactions
studied. The kN values for the reactions of SA amines, as well as
those of the pKa of their conjugate acids, were statistically
corrected with q ¼ 2 for piperazine (q ¼ 1 for all the other SA
amines) and p ¼ 2 for the conjugate acids of the amines, except
that for the piperazinium dication with p ¼ 4.[24] The parameter q
is the number of equivalent basic sites on the free amine and p is
the number of equivalent dissociable protons on the conjugate
acid of the amine.[25] The Brønsted-type plots are linear for the
reactions of both substrates with pyridines and for the reaction of
PClDTF with SA amines. The corresponding plot for the reaction
of the latter amines with NPClDTF is biphasic.
step) of the zwitterionic tetrahedral intermediate (Tꢂ) is the
rate-determining step for all the pKa range studied. These b
values are in agreement with those found in the stepwise
reactions of PClTF and NPClTF with pyridines,[14] SA amines,[15]
and quinuclidines in water.[16] They are also in accordance with
those obtained for the stepwise reactions of a series of aryl
chloroformates with SA amines[11,12] and quinuclidines[13] in
water and the pyridinolysis of phenyl and 4-nitrophenyl
chloroformates in acetonitrile,[26] where the formation of the
intermediate Tꢂ is the rate-determining step.
The biphasic curve for the reaction of NPClDTF with SA amines
in Fig. 2 was calculated by means of Eqn (5),[27] with pKa0 ¼ 7.7 and
log k0N ¼ 1.5 (parameters for the center of curvature), b1 ¼ 0.2 and
b2 ¼ 1.1 (the slopes at high and low amine basicity, respectively).
The shape of this plot is in accordance with a stepwise
mechanism through a zwitterionic tetrahedral intermediate
(Tꢂ) and a change in the rate-limiting step, from formation of
Tꢂ (k1 step in Scheme 2) to its breakdown to products (k2 step in
Scheme 2), as the amine basicity decreases.[27]
The slopes (b) of the linear Brønsted plots for the reactions of
PClDTF with SA amines and pyridines and those of NPClDTF with
pyridines are 0.30, 0.26, and 0.30, respectively. These values are in
accordance with a stepwise process (as in Scheme 2, where Nu
represents a pyridine or SA amine), whereby the formation (k1
0
0
log ðkN=kN Þ ¼ b2 ðpKa ꢁ pKa Þ ꢁ log ½ð1 þ aÞ=2ꢀ
(5)
0
log a ¼ ðb2 ꢁ b1Þ ðpKa ꢁ pKa
Þ
J. Phys. Org. Chem. 2009, 22 1030–1037
Copyright ß 2009 John Wiley & Sons, Ltd.
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E. A. CASTRO, M. GAZITUA AND J. G. SANTOS
Table 5. Values of pKa for the conjugate acids of secondary alicyclic (SA) amines and kN values for the reactions of SA amines with
phenyl chlorodithioformate (PClDTF) and 4-nitrophenyl chlorodithioformate (NPClDTF)a
kN (sꢁ1 Mꢁ1
)
SA amine
pb
qc
pKa
PClDTF
NPClDTF
Piperidine
Piperazined
1-(2-Hydroxyethyl)piperazine
Morpholine
1-Formylpiperazine
Piperazinium ion
Piperazinium ione
2
2
2
2
2
4
4
1
2
1
1
1
1
1
10.82
9.71
9.09
8.48
7.63
5.37
5.37
82 ꢂ 3
71 ꢂ 3
260 ꢂ 10
210 ꢂ 10
77 ꢂ 2
17 ꢂ 1
26 ꢂ 1
111 ꢂ 2
32 ꢂ 1
11.8 ꢂ 0.5
3.3 ꢂ 0.5
2.2 ꢂ 0.1
0.52 ꢂ 0.01
a Both the pKa and kN values were determined in 44 wt% ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl).
b Number of equivalent protons on the conjugate acid of the amine.
c Number of equivalent basic sites on the free amine.
d Value obtained at the 9.41–10.01 pH range.
e Value obtained at the 6.5–7.5 pH range with Eqns (3) and (4).
From these results, it can be concluded that the substitution of
an oxygen atom in chlorothionoformates by a sulfur atom (to
yield chlorodithioformates) does not change the mechanism of
their SA aminolysis or pyridinolysis (it remains stepwise and only
the rate limiting step for SA amines changes).
group from the tetrahedral intermediate (Tꢂ) becomes greater
and the amine leaves faster from Tꢂ (larger kꢁ1). Since the amine
cannot exert its push to expel the leaving group (it lacks an
electron pair), this means a larger kꢁ1/k2 ratio and, according to
Eqn (6),[30] a larger pK0a value.[28,29] It is not clear why the reactions
The fact that the pK0a value for the reaction of NPClDTF with SA
amines (pK0a ¼ 7.7) is larger than that for the reaction of the same
amines with PClDTF (pK0a ꢃca. 5) is in line with the results
obtained for the pyridinolysis of aryl 4-X-substituted thiolbenzo-
ates (ArS—CO—C6H4—X) in aqueous ethanol:[28] the greater the
electron-withdrawing ability of the nonleaving group, the larger
the pKa0 value. This has been explained in the following way:[28,29]
as the X substituent in the nonleaving phenyl group becomes
more electron-withdrawing, the push provided by the leaving
Table 6. Values of pKa for the conjugate acids of pyridines
and kN values for the reactions of pyridines with phenyl
chlorodithioformate (PClDTF) and 4-nitrorophenyl chloro-
dithioformate (NPClDTF)a
Figure 1. Brønsted-type plots obtained for the reactions of pyridines
with phenyl chlorodithioformate (PClDTF) (*) and 4-nitrophenyl chlor-
odithioformate (NPClDTF) (*) in 44 wt% aqueous ethanol, at 25.0 8C and
an ionic strength of 0.2 M (KCl)
kN (sꢁ1 Mꢁ1
)
Pyridine substituent
pKa
PClDTF
NPClDTF
4-Oxy
11.50
9.45
9.14
8.98
6.90
5.68
4.63
2.67
2.17
88.0 ꢂ 1.0
34.0 ꢂ 1.0
24.0 ꢂ 1.0
22.4 ꢂ 0.6
10.1 ꢂ 0.5
3.5 ꢂ 0.3
3,4-Diamino
4-Dimethylamino
4-Amino
4-Amino-3-bromo
3,4-Dimethyl
None
10.4 ꢂ 0.4
8.8 ꢂ 0.4
8.2 ꢂ 0.5
2.9 ꢂ 0.1
2.2 ꢂ 0.1
1.0 ꢂ 0.1
0.17 ꢂ 0.01
0.10 ꢂ 0.03
0.82 ꢂ 0.06
0.22 ꢂ 0.01
0.16 ꢂ 0.01
3-Carbamoyl
3-Chloro
Figure 2. Brønsted-type plots (statistically corrected) obtained for the
reactions of SA amines with phenyl chlorodithioformate (PClDTF) (*) and
4-nitrophenyl chlorodithioformate (NPClDTF) (*), in 44 wt% aqueous
ethanol, at 25.0 8C and an ionic strength of 0.2 M (KCl)
a Both the pKa and kN values were determined in 44 wt%
ethanol–water, at 25.0 8C, ionic strength 0.2 M (KCl).
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Copyright ß 2009 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009, 22 1030–1037

REACTIONS OF ARYL CHLORODITHIOFORMATES
Figure 4. Brønsted plots (statistically corrected) for the reactions of SA
amines with PClDTF (*, this work), phenyl chlorothionoformate (*,
Reference 15), and phenyl chloroformate (&, Reference 11)
Scheme 2.
of NPClDTF with pyridines did not exhibit a biphasic Brønsted
plot, apparently not showing the same tendency as found for SA
amines. An explanation would be that for pyridines the pK0a value
for their reactions with PClDTF is <<3 and the expected increase
of this value did not show up in the plot for NPClDTF, i.e., the pKa0
value for the latter was 3 or less. It is reasonable that the pK0a value
for pyridines is lower than that for SA amines, since it is known
that kꢁ1 for a given pyridine is lower than that for an isobasic SA
amine.[24] A lower k (and the same k2 for both amines)[29]
ꢁ1
means
a
smaller pK0a value, according to the following
equation:[30]
Figure 5. Brønsted plots (statistically corrected) for the reactions of SA
amines with NPClDTF (*, this work), 4-nitrophenyl chlorothionoformate
(*, Reference 15), and 4-nitrophenyl chloroformate (&, Reference 11)
0
log ðkꢁ1=k2Þ ¼ ðb2 ꢁ b1Þ ðpKa ꢁ pKaÞ
(6)
Figure 3 shows a comparison of the Brønsted-type plots
obtained for the pyridinolysis of PClDTF and NPClDTF in aqueous
ethanol (this work) with the corresponding plots found for the
same aminolysis of PClTF and NPClTF in water.[14]
theless, in view of the fact that both media are very similar, it is
doubtful that the reactivity difference can be entirely accounted
for by the change of solvent.
Considering (a) the greater electron withdrawal of PhS
(sP ¼ 0.07) than PhO (sP ¼ ꢁ0.03)[31] and (b) that pyridines are
considered relatively soft bases and that the thiocarbonyl group
of PClDTF and NPClDTF should be softer than that of PClTF and
NPClTF,[32,33] respectively, greater values of k1 for PClDTF relative
to PClTF should be expected. The larger k1 values observed for
the pyridinolysis of PClTF[14] relative to PClDTF (this study) can be
attributed to a steric hindrance caused by the second sulfur atom
in PClDTF. The greater k1 values found for the reactions of
NPClTF[14] relative to NPClDTF (this work) can be explained the
same way. On the other hand, the change of solvent, from
aqueous ethanol (reactions of dithioformates) to water (reactions
of thionoformates), should also increase the k1 values. Never-
Figure 4 shows a comparison of the Brønsted-type plot
obtained for the SA aminolysis of PClDTF in aqueous ethanol (this
work) and those of PClTF[15] and PClF[11] in water. Figure 5 shows
the same plots for the 4-nitrophenyl derivatives. It can be
observed in these figures that k1 increases according to the
sequence PClDTF < PClTF < PClF and NPClDTF < NPClTF < NPClF.
The highest reactivity shown by the formates, compared with
thionoformates and dithioformates, can be explained by the
same argument mentioned above: as sulfur atoms are changed
by oxygen atoms in the substrates, there is less steric hindrance
toward amine attack, and therefore, higher reactivity.
CONCLUSION
The reactions of pyridines and SA amines with phenyl and
4-nitrophenyl chlorodithioformates (PClDTF and NPClDTF,
respectively) show Brønsted-type plots in agreement with a
stepwise mechanism, through a zwitterionic tetrahedral inter-
mediate (Tꢂ).
The slope values of the Brønsted-type plots are in accordance
with the formation of a the Tꢂ intermediate as the rate-
determining step, except for the reaction of NPClDTF with SA
amines where there is a change in the rate-determining step,
from formation to breakdown of Tꢂ, as the amine basicity
decreases.
Figure 3. Brønsted plots for the pyridinolysis of PClDTF (*, this work),
PClTF (*, Reference 14), NPClDTF (&, this work), and NPClTF (&,
Reference 14)
J. Phys. Org. Chem. 2009, 22 1030–1037
Copyright ß 2009 John Wiley & Sons, Ltd.
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E. A. CASTRO, M. GAZITUA AND J. G. SANTOS
The substitution of the oxygen atoms in phenyl chloroformate
by sulfur atoms (to give the corresponding thiono and dithio
chloroformates, respectively) does not produce changes in the
reaction mechanism, but progressively reduces the reactivity
toward the amine.
band is attributed to the corresponding dithiocarbamate. Phenyl
dithiocarbamate formed with morpholine was identified as the
final product of the reaction of PClDTF with morpholine. This was
achieved by comparison of the UV–Vis spectra after completion
of this reaction with that of an authentic sample under the same
conditions.
For the reactions with some pyridines, an increase followed by
a slow decrease of a band centered at 315–340 nm is attributed to
the corresponding dithiocarbamate cation (CP).
EXPERIMENTAL
Materials
The pyridines and SA amines were purified as reported.[24] Phenyl
chlorodithioformate (PClDTF) is a commercial product and was
used as purchased. 4-Nitrophenyl chlorodithioformate (NPClDTF)
was synthesized as reported,[34,35] and identified as follows:
1H-NMR (400 MHz, CDCl3) 7.72 (d, 2H, J ¼ 8.9Hz) and 8.35 (d, 2H,
J ¼ 8.9Hz). 13C-NMR (100 MHz,) d ppm 124.85, 135.69, 138.70,
149.22, and 194.36.
Acknowledgements
We thank MECESUP of Chile (projects PUC-0004 and RED QUI-
MICA UCH-01) and FONDECYT of Chile (project 1060593) for
financial support. MG thanks CONICYT of Chile for a doctoral
fellowship.
The phenyl dithiocarbamate formed with morpholine was
prepared by the reaction of phenyl chlorodithioformate with
morpholine in acetonitrile, following the general method used for
the synthesis of aryl carbamates.[11] The product obtained was
identified by its melting point and 1H-NMR and 13C-NMR
analyses: mp 139–140.5 8C (lit.[36] mp 141 8C; lit.[37,38] mp
138–141 8C). 1H-NMR (400 MHz, CDCl3) 7.45–7.52 (5H), 4.21
(4H), and 3.82 (4H). 13C-NMR (100 MHz,) d ppm 51.30, 66.30,
129.18, 130.22, 130.97, 137.08, and 198.02.
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Copyright ß 2009 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009, 22 1030–1037

REACTIONS OF ARYL CHLORODITHIOFORMATES
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