Kinetics and Mechanism of the Aminolysis of Phenyl and 4-Nitrophenyl Chlorothionoformates

Article abstract of DOI:10.1021/jo970276y

The reactions of a series of secondary alicyclic amines with the title substrates are subjected to a kinetic investigation in aqueous solution, 25 °C, ionic strength 0.2 M (maintained with KCl). Under amine excess pseudo-first-order rate coefficients (k_obsd) are found. The plots of k_obsd against concentration of free amine at constant pH are linear, with the slopes (k_N) independent of pH. The Broensted-type plots obtained (log k_N vs amine pK_a) for the aminolysis of both substrates are linear with the same slope, β = 0.26. From this value, the kinetic law, and the analysis of products, it is deduced that these reactions proceed through a zwitterionic tetrahedral addition intermediate (T^±) on the reaction path, and its formation is the rate-determining step. From a comparison of the present reactions with the concerted aminolysis of substituted phenyl chloroformates in acetonitrile it is inferred that the change of S^- by O^- in T^± and that of water by acetonitrile as solvent destabilizes T^± in such a way that the stepwise reaction becomes enforced concerted.

Full text of DOI:10.1021/jo970276y

J . Org. Chem. 1997, 62, 4395-4397
4395
Kin etics a n d Mech a n ism of th e Am in olysis of P h en yl a n d
4
-Nitr op h en yl Ch lor oth ion ofor m a tes
Enrique A. Castro,* Mar ´ı a Cubillos, and J os e´ G. Santos*
Facultad de Qu ı´ mica, Pontificia Universidad Cat o´ lica de Chile, Casilla 306, Santiago 22, Chile
Received February 14, 1997X
The reactions of a series of secondary alicyclic amines with the title substrates are subjected to a
kinetic investigation in aqueous solution, 25 °C, ionic strength 0.2 M (maintained with KCl). Under
amine excess pseudo-first-order rate coefficients (kobsd) are found. The plots of kobsd against
concentration of free amine at constant pH are linear, with the slopes (k
N
) independent of pH.
The Br o¨ nsted-type plots obtained (log k vs amine pK ) for the aminolysis of both substrates are
N
a
linear with the same slope, â ) 0.26. From this value, the kinetic law, and the analysis of products,
it is deduced that these reactions proceed through a zwitterionic tetrahedral addition intermediate
(
(
T ) on the reaction path, and its formation is the rate-determining step. From a comparison of
the present reactions with the concerted aminolysis of substituted phenyl chloroformates in
-
-
(
acetonitrile it is inferred that the change of S by O in T and that of water by acetonitrile as
(
solvent destabilizes T in such a way that the stepwise reaction becomes enforced concerted.
In tr od u ction
(Aldrich) was added slowly under nitrogen atmosphere. The
product, lithium 4-nitrophenoxide was rapidly transferred to
a compensation funnel, under nitrogen. In another Schlend
round-bottomed flask, thiophosgene (Aldrich, 4 mL) was
dissolved in anhydrous THF (10 mL) under nitrogen and the
flask placed in an ethanol-liquid nitrogen bath. The com-
pensation funnel was attached to the flask and the lithium
Although there has been much interest on the kinetics
and mechanism of the hydrolysis and solvolysis of alkyl
1
,2
1,3
and aryl chloroformates and fluoroformates, less is
known on the aminolysis of these compounds.4
,5
More-
over, to our knowledge there are no reports on the
kinetics and mechanism of the aminolysis of either alkyl
or aryl chlorothionoformates.
There are apparently conflicting conclusions regarding
the mechanisms of some of the above reactions. Those
of methyl chloroformate with aliphatic and aromatic
primary amines and pyridines in water have been
4
2
-nitrophenoxide solution added dropwise with stirring during
h. The mixture was left overnight with stirring under
nitrogen at ambient temperature. Chloroform (50 mL) was
added to this mixture and the solution washed with water.
The organic layer was dried with MgSO and filtered under
4
vacuum and the solvent evaporated off. The crystallized
7
NPClTF melted at 57 °C (lit. mp 61-63 °C) and was identified
as follows:
NPClTF: H NMR (200 MHz, CDCl
claimed to be stepwise, through the formation of a
1
zwitterionic terahedral intermediate.4
b,c
3
) δ 7.35 (sd, 2H, J )
On the other
1
3
9
.2 Hz), 8.36 (sd, 2H, J ) 9.2 Hz); C NMR (50 MHz, CDCl
3
)
hand it was found that the reactions of anilines with
substituted phenyl chloroformates in acetonitrile are
governed by a concerted mechanism.5
δ 122.71 (C-2/6), 125.78 (C-3/5), 146.49 (C-4), 158.15 (C-1),
1
1
2
84.66 (CdS); IR (KBr) 1552 (CdC), 1492 and 1345 (CsNO ),
244 (CdS) cm
-1
.
In order to clarify the mechanisms of the above
reactions and to assess the influence of the carbonyl or
thiocarbonyl group of the substrate and the role of the
solvent, we investigate in this work the kinetics of the
reactions of a series of secondary alicyclic amines with
the title substrates in water.
Kin etic Mea su r em en ts. These were performed spectro-
photometrically by following the production of the aryl thiono-
carbamates at 245 and 320 nm for the aminolysis of PClTF
and NPClTF, respectively. The reactions of both substrates
with piperidine and piperazine were measured using an
Applied Photophysics SF-17 MV stopped-flow spectrophotom-
eter. The reactions with the other amines were followed by
means of a Hewlett Packard HP 8453 diode array spectropho-
tometer attached to a Hi-Tech SFA-20 rapid kinetics accesory.
The reactions were studied under the following conditions:
aqueous solutions, 25.0 ( 0.1 °C, ionic strength 0.2 M
Exp er im en ta l Section
Ma ter ia ls. The amines were purified as reported.6 Phenyl
chlorothionoformate (PClTF) was from Sigma and used as
purchased. 4-Nitrophenyl chlorothionoformate (NPClTF) was
synthesized as follows: To a solution of 4-nitrophenol (4.6 g,
(
maintained with KCl), and at least a 10-fold excess of total
amine over the substrate.
Pseudo-first-order rate coefficients (kobsd) were found through-
3
3 mmol) dissolved in THF (20 mL) in a Schlend round-
out, by means of the method described.6 The experimental
bottomed flask, a solution (13.6 mL) of 2.5 M butyllithium
conditions of the reactions and the kobsd values obtained are
shown in Tables 1 and 2.
X
Abstract published in Advance ACS Abstracts, May 15, 1997.
P r od u ct Stu d ies. Phenyl thionocarbamates of piperidine
and morpholine were identified as the final products of the
reactions of PClTF with these two amines. This was carried
out by comparison of the UV-vis spectra after completion of
these reactions with those of authentic samples under the
same experimental conditions. The UV-vis spectra after the
end of the reactions of both substrates with the above two
amines were also compared with those after completion of the
reactions of bis phenyl and bis 4-nitrophenyl thionocarbonates
(
1) Kevill, D. N. In The Chemistry of Acyl Halides; Patai, S., Ed.;
Interscience: New York, 1972; p 381.
2) Queen, A. Can. J . Chem. 1967, 45, 1619. Moodie, R. B.; Towill,
(
R. J . Chem. Soc., Perkin Trans. 2 1972, 184. Koo, I. S.; Yang, K.; Kang,
K.; Oh, H. K.; Lee, I. Bull. Korean Chem. Soc. 1996, 17, 520.
(
3) Olofson, R. A. Pure Appl. Chem. 1988, 60, 1715. Kevill, D. N.;
Kyong, J . B. J . Org. Chem. 1992, 57, 258.
4) (a) Hall, H. K., J r. J . Am. Chem. Soc. 1957, 79, 5439. (b) Castro,
(
E. A.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1974, 658. (c) Bond,
P. M.; Castro, E. A.; Moodie, R. B. J . Chem. Soc., Perkin Trans. 2 1976,
8.
6
(
5) Yew, K. H.; Koh, H. J .; Lee, H. W.; Lee, I. J . Chem. Soc., Perkin
Trans. 2 1995, 2263.
6) Castro, E. A.; Ureta, C. J . Org. Chem. 1989, 54, 2153.
(7) Hilgetag, G.; Philippson, R. Monatsber. Deut. Akad. Wiss. Berlin
1964, 6, 585; Chem. Abstr. 1965, 62, 5165h.
(
S0022-3263(97)00276-4 CCC: $14.00 © 1997 American Chemical Society

4
396 J . Org. Chem., Vol. 62, No. 13, 1997
Castro et al.
Ta ble 1. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
Ta ble 3. Va lu es of th e p Ka of th e Con ju ga te Acid s of
Secon d a r y Alicyclic Am in es a n d kN for th e Am in olysis of
P h en yl Ch lor oth ion ofor m a te (P ClTF ) a n d 4-Nitr op h en yl
Ch lor oth ion ofor m a te (NP ClTF )a
th e Am in olysis of P h en yl Ch lor oth ion ofor m a te (P ClTF )a
no. of
runs
b
2
10 [N]tot,c M
obsd, s-1
amine
piperidine
pH
F
N
k
kN, s- M-1
1
10.92 0.32
1.22 0.49
9.64 0.33
1.0-10
0.2-10
0.10-10
0.10-10
0.06-1.0
0.06-0.4
0.06-0.6
0.7-10
0.2-13
0.08- 8.0
0.1-13
0.12-0.52
0.13-0.48
0.17-0.56
0.001-0.005
0.001-0.008
0.002-0.01
0.05-0.3
5
6
5
5
6
7
6
6
7
7
7
7
6
6
8
7
1
amine
pKa
PClTF
NPClTF
piperazine
piperidine
piperazine
11.24
9.94
9.38
8.78
7.98
5.81
530 ( 23
514 ( 18
240 ( 8
130 ( 4
116 ( 4
24 ( 1
1058 ( 27
962 ( 27
432 ( 18
216 ( 6
177 ( 7
48 ( 1
9
.94 0.50
-(2-hydroxyethyl)- 9.08 0.33
piperazine 9.38 0.50
.68 0.67
morpholined
1
1
-(2-hydroxyethyl)piperazine
morpholine
-formylpiperazine
9
1
6.50 0.0052 0.15-0.7
piperazinium ion
6
7
.80 0.010
.10 0.020
0.06-0.6
0.05-0.5
0.06-0.6
0.06-0.6
0.06-0.5
0.07-0.7
0.07-1.0
a
Values of both pK and kN in aqueous solution, at 25 °C, ionic
a
1
-formylpiperazine 7.68 0.33
strength 0.2 M (KCl).
7
8
.98 0.50
.28 0.67
0.06-0.4
0.06-0.4
0.006-0.05
0.007-0.13
piperazinium ion
5.51 0.33
5
6
.81 0.50
.11 0.67
0.07- 0.85 0.009-0.14
a
In aqueous solution at 25.0 °C, ionic strength 0.2 M (KCl).
b
c
Free amine fraction. Concentration of total amine (free base
d
-3
plus protonated forms). In the presence of 5 × 10 M phosphate
buffer.
Ta ble 2. Exp er im en ta l Con d ition s a n d kobsd Va lu es for
th e Am in olysis of 4-Nitr op h en yl Ch lor oth ion ofor m a te
a
(
NP ClTF )
no. of
runs
b
10 [N]tot,c M
2
k
obsd, s-1
amine
piperidine
pH
F
N
10.92 0.32
1.22 0.49
9.64 0.33
1.0-10
0.2-10
0.10-10
0.10-10
0.06-1.0
0.06-0.4
0.06-0.6
1.0-18
0.3-26
0.16- 17
0.19-24
0.15-0.85
0.19-0.78
0.23-1.0
5
5
5
5
6
6
6
6
7
7
7
7
6
7
7
7
1
piperazine
9
.94 0.50
-(2-hydroxyethyl)- 9.08 0.33
piperazine 9.38 0.50
.68 0.67
morpholined
1
9
6.50 0.0052 0.15-0.65 0.002-0.008
.80 0.010
.10 0.020
6
7
0.06-0.6
0.05-0.5
0.06-0.6
0.06-0.6
0.06-0.5
0.07-0.85 0.01-0.14
0.07-0.85 0.02-0.20
0.07-0.85 0.02-0.30
0.002-0.015
0.003-0.022
0.08-0.44
0.08-0.61
0.09-0.62
1
-formylpiperazine 7.68 0.33
7
8
.98 0.50
.28 0.67
piperazinium ion
5.51 0.33
5
6
.81 0.50
.11 0.67
a
In aqueous solution at 25.0 °C, ionic strength 0.2 M (KCl).
b
c
Free amine fraction. Concentration of total amine (free base
F igu r e 1. Br o¨ nsted-type plots (statistically corrected) ob-
tained in the reactions of secondary alicyclic amines with
NPClTF (b) and PClTF (O) in water, at 25 °C, ionic strength
d
-3
plus protonated forms). In the presence of 5 × 10 M phosphate
buffer.
0
.2 M (KCl). The slope is â ) 0.26 for the reactions of both
with the same amines. It was inferred from these comparisons
that the phenyl and 4-nitrophenyl thionocarbamates deriva-
tives of these amines are one of the products of these reactions.
substrates.
compared to the aminolysis term in eq 2. Throughout
the reactions studied the k
independent, and are shown in Table 3.
The Br o¨ nsted-type plots (statiscally corrected) ob-
tained with de k data are linear with slopes â ) 0.26 (
.1 for the reactions of both substrates (see Figure 1).
The value of the slopes is in agreement with those found
N
values obtained were pH
Resu lts a n d Discu ssion
6
,8
The kinetic law found for the present reactions is given
by eqs 1 and 2, under amine excess, where P, S, and NH
represent the aryl thionocarbamate product, the sub-
N
0
9
10
in the aminolysis of aryl acetates, diaryl carbonates,
d[P]
4
c
11
methyl chloroformate, acetyl chloride, aryl thiol-
)
kobsd[S]
(1)
(2)
dt
kobsd ) k + k [NH]
6,12
13
acetates,
and O-alkyl aryl dithiocarbonates, thiol-
carbonates,14 and thionocarbonates in aqueous solution,
15
o
N
(
8) Bell, R. P. The Proton in Chemistry, Methuen: London, 1959; p
strate, and the free secondary amine, respectively, and
obsd is the pseudo-first-order rate coefficient; k and k
N
are the rate coefficients for hydrolysis and aminolysis of
the substrate, respectively. The latter values were found
as the intercept and slope, respectively, of linear plots of
159.
(
9) Satterthwait, A. C.; J encks, W. P. J . Am. Chem. Soc. 1974, 96,
k
o
7
6
018.
(10) Gresser, M. J .; J encks, W. P. J . Am. Chem. Soc. 1977, 99, 6963.
(11) Palling, D. J .; J encks, W. P. J . Am. Chem. Soc. 1984, 106, 4869.
(
3.
(
12) Castro, E. A.; Ureta, C. J . Chem. Soc., Perkin Trans. 2 1991,
k
obsd against the free-amine concentration at constant pH.
13) Castro, E. A.; Ib a´ n˜ ez, F.; Salas, M.; Santos, J . G.; Sep u´ lveda,
For all the reactions, the value of k was negligible
o
P. J . Org. Chem. 1993, 58, 459.

Aminolysis of Phenyl and 4-Nitrophenyl Chlorothionoformates
when the formation of a zwitterionic tetrahedral addition
J . Org. Chem., Vol. 62, No. 13, 1997 4397
that the reactions of secondary alicyclic amines with
(
intermediate (T ) is the rate-determining step (â ) 0.1-
O-ethyl 2,4,6-trinitrophenyl dithiocarbonate are con-
1
8
0
.3). A larger value of the Bronsted slope (â ) 0.8-1.0)
certed in aqueous ethanol, whereas the same reactions
1
3
has been found in the above aminolyses when the
are stepwise in water. It was concluded that expulsion
(
(
expulsion of the leaving group from
T
is rate
of the amine from T should be faster in the less polar
determining.6
,9-14
solvent, and the nucleofugality of the leaving group of
the substrate should not change significantly with the
solvent polarity.18 This fact should render the intermedi-
According to the rate law obtained, the analysis of
products, and the Bronsted-type plots found for the
reactions under investigation, the mechanism of these
reactions can be described by eq 3, where Ar is either
phenyl or 4-nitrophenyl and NH represents a secondary
1
8
ate more unstable kinetically in the less polar solvent.
The above two arguments can explain the reason for
the different mechanisms followed by the aminolysis of
alicyclic amine. In eq 3 the k
1
step is rate limiting.
5
phenyl chloroformates in acetonitrile and the reactions
under the present study.
The aminolyses of methyl chloroformate4b,c and acetyl
chloride11 in water have been shown to be stepwise
processes. It could be possible that the aminolysis of aryl
chloroformates in water were concerted due to the kinetic
(
destabilization of the intermediate T involved in the
latter reactions. Taking into account that the inductive
The higher reactivity of NPClTF compared to PClTF
toward these amines (Figure 1) for the formation of
intermediate 1 (eq 3) is reasonable in terms of the larger
(
effects are more important in T than the resonance
19
effects, this destabilization should arise from the larger
electron-withdrawing inductive ability of the phenoxy
electron-withdrawing ability of the p-NO
(
2
substituent
20
20
group (σ
I
) 0.37) relative to that of methyl (σ ) 0.01)
I
relative to H), both by resonance and inductive effects.1
6
20
and methoxy (σ ) 0.29). This fact should render the
I
This fact renders the thiocarbonyl carbon of NPClTF
more positive than that of PClTF and therefore more
susceptible to amine attack.
(
central carbon of the intermediate T with phenoxy more
positively charged than those with methyl and methoxy,
facilitating therefore the formation of the CdO double
bond and the amine expulsion from the intermediate. At
present we are beginning a kinetic study on the amin-
olysis of substituted phenyl chloroformates in water in
order to investigate whether there is a change in mech-
anism from stepwise for the reactions of acetyl chloride
and methyl chloroformate in water to concerted for those
of aryl chloroformates in the same solvent.
It has been reported that the reactions of substituted
phenyl chloroformates with anilines in acetonitrile are
concerted (although the possibility of a two-step mech-
5
anism was not entirely precluded). The apparent dis-
crepancy with our work can be clarified as follows:
-
(
i) It is known that the change of O- by S in the
(
zwitterionic tetrahedral addition intermediate (T ) makes
it less unstable. This has been explained by the superior
-
-
(
ability of O (relative to S ) in T to form a double bond
Ack n ow led gm en t. We thank FONDECYT of Chile
for financial assistance to this work. We are also
grateful to Dr. E. Buj a´ n de Vargas and Dr. Rita H. de
Rossi from Facultad de Ciencias Qu ´ı micas, Universidad
Nacional de C o´ rdoba, Argentina, for the facilities given
for the use of the stopped-flow spectrophotometer.
1
7
and expel faster both its leaving and amino groups.
(
(
ii) The intermediate T should be less stable in
acetonitrile than in water due to its zwitterionic nature
and the high polarity of water. In fact we have found
(
14) Castro, E. A.; Cubillos, M..; Santos, J . G. J . Org. Chem. 1994,
5
6
9, 3572. Castro, E. A.; Pizarro, M. I.; Santos, J . G. J . Org. Chem. 1996,
1, 5982.
J O970276Y
(
15) Castro, E. A.; Cubillos, M.; Santos, J . G. J . Org. Chem. 1996,
1, 3501.
16) Hammett, L. P. Physical Organic Chemistry, 2nd ed; McGraw-
Hill: New York, 1970; p 358.
17) Castro, E. A.; Ib a´ n˜ ez, F.; Santos, J . G.; Ureta, C. J . Org. Chem.
993, 58, 4908.
6
(18) Castro, E. A.; Cubillos, M.; Mu n˜ oz, G.; Santos, J . G. Int. J .
Chem. Kinet. 1994, 26, 571.
(19) Sayer, J . M.; J encks, W. P. J . Am. Chem. Soc. 1973, 95, 5637.
Fox, J . P.; J encks, W. P. J . Am. Chem. Soc. 1974, 96, 1436.
(20) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165.
(
(
1