Kinetic study of the formation of N-chloro compounds using N-chlorosuccinimide

Article abstract of DOI:10.1002/poc.3278

Second-order rate constants were determined for the chlorination reaction of 2,2,2-trifluoethylamine and benzylamine with N-chlorosuccinimide at 25 °C and an ionic strength of 0.5 M. These reactions were found to be of first order in both reagents. According to the experimental results, a mechanism reaction was proposed in which a chlorine atom is transferred between both nitrogenous compounds. Kinetics studies demonstrate that the hydrolysis process of the chlorinating agent does not interfere in the chlorination process, under the experimental conditions used in the present work. Free-energy relationships were established using the results obtained in the present work and others available in the literature for chlorination reactions with N-chlorosuccinimide, being the pK_a range included between 5.7 and 11.22. Copyright

Full text of DOI:10.1002/poc.3278

Research Article
Received: 31 July 2013,
Revised: 5 December 2013,
Accepted: 15 December 2013,
Published online in Wiley Online Library: 20 January 2014
(wileyonlinelibrary.com) DOI: 10.1002/poc.3278
Kinetic study of the formation of N-chloro
compounds using N-chlorosuccinimide
Cristina Pastorizaa*, Juan Manuel Anteloa, Juan Crugeirasa
and Angeles Peña-Gallegob
Second-order rate constants were determined for the chlorination reaction of 2,2,2-trifluoethylamine and benzylamine with
N-chlorosuccinimide at 25 °C and an ionic strength of 0.5 M. These reactions were found to be of first order in both reagents.
According to the experimental results, a mechanism reaction was proposed in which a chlorine atom is transferred between
both nitrogenous compounds. Kinetics studies demonstrate that the hydrolysis process of the chlorinating agent does
not interfere in the chlorination process, under the experimental conditions used in the present work. Free-energy
relationships were established using the results obtained in the present work and others available in the literature for
chlorination reactions with N-chlorosuccinimide, being the pKa range included between 5.7 and 11.22. Copyright ©
2014 John Wiley & Sons, Ltd.
Keywords: free relationships; kinetics and mechanism; N-chloramines; N-chlorination; N-chlorosuccinimide
work with bibliographic results. On the other hand, we have at
our disposal information regarding the kinetic studies of these
INTRODUCTION
N-Chloro compounds are reagents that are frequently used in
the intermediate steps of the synthesis of organic com-
pounds.[1–7] Sodium hypochlorite, N-chlorosuccinimide (NCS),
chloramine-T, chloramine-B, and tert-butyl hypochlorite are
some of the most common reagents used to obtain N-chloro
compounds.[8–15] All of them contain one electrophile chlo-
rine atom, positive chlorine, able to react with amino acids,
amines, amides, and other nitrogenous compounds to form
the corresponding N-chloro compound. These reactions occur
by the rupture of the N—H bond and formation of the N—Cl
bond.
These N-chloro compounds have oxidizing properties and
bactericidal capacity because of the existence of the N—Cl bond.
To this regard, some of them are used directly as disinfectants or
in the development of different formulations to be used as bac-
tericides.[16–22]
amines with other chlorinating agents (HOCl, N-chloro-N-methyl-
p-toluenesulfonamide), so it is also interesting to compare the
effectiveness of the different N-chlorinating agents because of
the great importance of these N-chlorination reactions in envi-
ronmental and biochemical processes.[24–30]
EXPERIMENTAL METHOD
Reagents
The NCS solution was prepared directly using a previously recrystallized
Merck commercial product.[31] Its purity was iodometrically deter-
mined.[32] The stock solution with a concentration of 0.02 M was pre-
pared every day, using acetonitrile as a solvent. Dilute solutions were
prepared by diluting the stock solution.
The 2,2,2-trifluoroethylamine solutions were prepared using 2,2,2-
trifluoroethylamine hydrochloride, 98%, obtained from Aldrich commer-
cial products. Different aqueous solutions of 2,2,2-trifluoroethylamine
were prepared by adding different amounts of NaOH to obtain different
percentages of free amine in the medium but always maintaining the to-
tal concentration at 0.5 M.
In the present work, we have summarized the results obtained
in the kinetic study of the chlorination reactions of 2,2,2-
trifluoroethylamine and benzylamine with NCS to form the
corresponding N-chloramines.
Hitherto, no information was found about the kinetic studies
of the chlorination reaction of 2,2,2-trifluoroethylamine with
NCS. So that it is interesting to study the behavior of this nitrog-
enous compound because it has a pKa lower than other nitroge-
nous compounds studied, for which there is literature available
and thus, extending the range of pKa studied in the formation re-
action of N-chloramines with NCS. The study of the chlorination
of benzylamine with NCS is also included in the present work be-
cause the kinetic information available for this amine is limited
and contradictory.[23]
In the present work, we have used an experimental technique
suitable to study fast reactions with a half-time of milliseconds.
The values of the rate constants obtained allow us to justify a
possible reaction mechanism. Also, they allow us to establish struc-
ture–reactivity relationships, comparing the results obtained in this
Aqueous solutions of benzylamine and 4-methylbenzylamine 0.2 M
were prepared also using Aldrich commercial products.
Several buffer solutions were used to control the pH of the medium:
CH3COOH/CH3COO–, H2PO4–/HPO42–, HPO42–/PO43–, and H3BO3/H2BO3
–
.
* Correspondence to: Cristina Pastoriza, Departamento de Química Física, Facultad
de Química, Universidad de Santiago de Compostela, 15782 La Coruña, Spain.
E-mail: cinecris@gmail.com
a C. Pastoriza, J. M. Antelo, J. Crugeiras
Departamento de Química Física, Facultad de Química, Universidad de
Santiago de Compostela, 15782 La Coruña, Spain
b A. Peña-Gallego
Departamento de Química Física, Facultad de Química, Universidad de Vigo,
36310 Vigo, Spain
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Copyright © 2014 John Wiley & Sons, Ltd.

C. PASTORIZA ET AL.
All of them were prepared with Aldrich products. A solution of 2 M NaClO4
was used to control the ionic strength.
place. The N-chloro compounds present a typical band at
250 nm.[9,40–42] The wavelengths chosen were 240 and 250 nm for
the N-chlorobenzylamine and the N-chloro-2,2,2-trifluoroethylamine,
respectively.
Instrumental
A VARIAN CARY 1 Bio spectrophotometer was used for the preliminary
studies, equipped with a thermostated cell holder and quartz cells with
a 1 cm path length and a capacity of 3 cm3. This spectrophotometer
was also used to monitor the chlorination reaction of 2,2,2-
trifluoroethylamine in the presence of a CH3COOH/CH3COO– solution. A
stopped-flow spectrophotometer, Applied Photophysics DX.17MV, was
used to monitor the rest of the reactions. A mixed asymmetric (1 : 25)
was used to minimize the solvent effect. The thermostat used, a Selecta
Frigiterm S-382, ensured a consistency in temperature of 0.1 °C. A work-
station allowed us to obtain the absorbance-time data that were sent to
a computer equipped with a program to analyze the data.
All experiments were repeated between four and seven times. The
values for the rate constants of pseudo-first order included in the tables
are the average value of all values obtained experimentally. The devia-
tions obtained in each case were less than 5%. In those cases where
the deviations were greater, the experiment was refused and repeated.
The pH measurements were made with a pH meter, PHM 82 STAN-
DARD, Radiometer Copenhagen, equipped with a combined electrode
GK2401C, thermostated at 25 °C. The pH meter was calibrated with stan-
dard solutions of pH 4.01, 7.02, and 9.21 supplied by Crison.
Reaction order with respect to N-chlorosuccinimide
All studies were performed under isolated conditions using the
amine as reagent in excess. Therefore, the amine concentration
can be considered practically constant during the reaction, and
it can also be included in the rate constant (kobs). Moreover,
the use of buffer solutions in the experiments allowed the pH
to be maintained constant during the reaction; as a result, the
term [H+] can also be included in kobs
.
In accordance with the previous texts, the equation rate could
be written as:
d½NCSꢁ d½R1NHClꢁ
b
v ¼ ꢀ
¼
¼ kobs ½NCSꢁ
(1)
(2)
dt
dt
c
a
kobs ¼ k ½R1NH2ꢁ ½Hþꢁ
To verify the order of reaction with respect to the NCS concen-
tration, the data (Abs versus t) were fitted to the first-order inte-
grated equation written exponentially (Eqn 3) using the software
included in the data control programs of the stopped-flow spec-
trophotometer.
The data treatment was performed using a spreadsheet (Grafit 5.0), which
has allowed obtain the different magnitudes from experimental data.
In the tables, all values are expressed with corresponding significant
figures. Such that all digits are true, and the last digit is uncertain. To
propagation uncertainty, in mathematical calculations, we have followed
the criteria found in literature.[33–35]
obs t
At ¼ A∞ þ ðAo ꢀ A∞Þꢂeꢀk
(3)
RESULTS
Where A0, At, and A∞ are the absorbance reading at zero, t,
and infinite times, respectively, and kobs is the pseudo-first-order
rate constant. The good fit of the data to this equation allows us
to confirm that the reaction order with respect to the NCS con-
centration is one (b = 1) and to determine the kobs value.
Preliminary studies: wavelength selection
By mixing the NCS solution in acetonitrile with the aqueous
solution of amine, the formation process of the N-chloramine
occurs quickly, followed by a slower process of decomposition
(Scheme 1).
Formation reaction of N-chloro-2,2,2-trifluoroethylamine
Reaction order with respect to 2,2,2-trifluoroethylamine
These two processes happen with very different reaction rates,
so it is possible to study their kinetics independently. The half-
time for the formation step in the range of pH = 5–7 is less than
10 s (t1/2 < 10 s). The N-chloramines obtained from aliphatic
amines in a neutral medium are quite stable, increasing their de-
composition rate in a strong acid medium or basic medium.[36–39]
To select the suitable conditions for kinetic monitoring, a prelimi-
nary spectrophotometric study of all the reactants and of the reac-
tion mixture was performed between 200 and 400 nm. The
superposition of all of them allows us to justify that, upon mixing
of the reactants, the formation of the N-chloro compound takes
In order to investigate the influence of the amine concentration on
the rate constant and thus determine the reaction order with re-
spect to 2,2,2-trifluoroethylamine, we designed a set of experiments
at different initial concentrations of amine. These were carried out
at five different values of pH. The amine concentration was modi-
fied to each pH, while the other parameters were maintained con-
stant (temperature, ionic strength, NCS concentration).
Figure 1 shows the results obtained. In this representation, the
rate constant (kobs) increases with increasing amine concentra-
tion, for each pH value. The linear relationship between kobs
and the amine concentration allows us to confirm that the reac-
tion is of first order with respect to the amine concentration,
a = 1. These values show the increase of the rate constant with
increasing pH.
Moreover, we can determine the rate constant of second-or-
der k2nd (k2nd = kobs/[R1NH2]) from the slope value obtained in
the linear regression analysis for each pH studied.
Influence of buffer solution concentration
A set of experiments was designed to study the reaction outside
the range of pH, where the amine solution can be used as a buffer
Scheme 1. General equation of the reaction of N-chlorosuccinimide
(NCS) with nitrogenous compounds
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DETERMINATION OF SECOND-ORDER RATE CONSTANTS
Figure 1. Plot kobs versus [Am]T. [NCS] = 1.0ꢃ 10ꢀ3 M. (♦) pH = 4.95, (●)
pH = 5.06, (▲) pH = 5.40, (■) pH = 6.01, (▼) pH = 6.27
Figure 2. Plot kobs versus [Buffer]T. [NCS]=1.0ꢃ 10ꢀ3 M, [Am]T =0,01M,
(▲) pHm =4.43 (CH3COOH/CH3COO–), (●) pHm =6.59 (H2PO4–/HPO42–),
(○) pHm =7.27 (H2PO–4/HPO42–)
2–
solution (4.70–6.70), using buffer solutions of H2PO4–/HPO4
(pKa = 6.8) and CH3COOH/CH3COO– (pKa = 4.58).
A solution of amine hydrochloride was used to prepare the re-
action mixture. Consequently, to carry out this study it was nec-
essary to neutralize the amine solution by adding the same
amount of NaOH as of amine. Thus, we can ensure the function-
ing of the external buffer solution of phosphate and we can
therefore reach pH values around 6.8. Two different buffer
2–
solutions of H2PO4 –/HPO4 were used with different fractions
of free base, 0.5 and 0.75. With each of these solutions, a set of
experiments was carried out varying the total concentration of
the buffer, between 0.01 and 0.1 M. In the case of the acetic acid
buffer, the amine solution was not previously neutralized.
Figure 2 shows the results obtained for the different buffer
2–
solutions of H2PO4–/HPO4 and CH3COOH/CH3COO–. In this
figure, we can observe that the rate constant increases with
increasing buffer concentration. The kobs value, extrapolated to
zero buffer concentration, corresponds to the value of the rate
constant independent of the buffer concentration.
Figure 3. Influence of pH on k2nd in the formation of N-chloro-2,2,
2-trifluoroethylamine. [NCS] = 10ꢀ3 M. (■) CH3COOH/CH3COO–, (▲)
H2PO4 –/HPO4 2–, (●) CF3CH2NH3+/CF3CH2NH2
Influence of pH
The values of the second-order rate constants (k2nd), obtained
from the linear regression analysis in the previous influence,
are represented versus pH (Fig. 3). In this figure, a nonlinear in-
crease of the rate constant with the pH can be observed. The
rate constant increases with increasing pH, to high proton con-
centrations, but it tends to reach a constant value and indepen-
dent of the proton concentration. These results seem to indicate
that there is a linear relationship only up to a pH less than the
pKa of amine, with a dependence c = ꢀ1 (Eqn 4). In the present
work, we try to justify this complex dependence from the reac-
tion mechanism.
time data show that the reaction is first order with respect to
the NCS concentration. The value of the pseudo-first-order rate
constant (kobs) was determined for each experiment. The effect
of the amine concentration on the rate constant was studied
using a buffer solution of phosphate acid, H2PO4–/HPO42–, to main-
tain the pH of the medium constant during the reaction. The
experimental results obtained allow us to verify that the reaction is
first order with respect to the benzylamine concentration, a = 1.
The experimental results are listed in Table 1.
The influence of pH on the rate constant was studied within a
pH range of 5.8–11.45 at 25 °C, using different buffer solutions to
reach the desired pH. In all of the series of experiments, the ionic
strength was maintained constant, as well as the concentrations
of NCS, benzylamine, and of the buffer solution.
c
k2nd ¼ k ½Hþꢁ
(4)
Figure 4 shows the pH dependence of the experimental rate
constants. In this representation, log kobs against pH, we can
see that the rate constant increases linearly with increasing pH
at pH < 9, but at pH > 10, the rate constant reaches a constant
Formation reaction of N-chlorobenzylamine
The kinetic study of this reaction was carried out in isolated con-
ditions, using the amine as reagent in excess. The absorbance-
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C. PASTORIZA ET AL.
Table 1. Influence of [Benzylamine] on kobs. [NCS]=1.0ꢃ 10ꢀ4 M,
the Arrhenius equation and the equation derived from the Eyring
theory activated complex. This allows us to obtain the activation
parameters for the formation reaction of the N-chlorobenzylamine:
Ea = (67.3 0.6)ꢃ 103 J molꢀ1, ΔS≠ = (ꢀ33 2) J Kꢀ1 molꢀ1, and
[H2PO4 –/HPO4 2–]T = 0.1 M
[Benzylamine]/10ꢀ3 M
kobs/sꢀ1
pH
ΔH≠ = (64.8 0.5)ꢃ 103 J molꢀ1
.
1.00
3.25
5.50
7.75
10.00
1.06 0.04
3.7 0.1
7.3 0.2
9.5 0.3
11.6 0.3
6.72
6.79
6.86
6.89
6.85
In the present work, we have also studied the reaction of NCS
with 4-methylbenzylamine. The results obtained were similar to
those obtained in the reaction of benzylamine with NCS. The re-
action was found to be of first order with respect to NCS concen-
tration, and a complex dependence of the rate constant on the
pH was also found.
MECHANISM
In order to establish the mechanism of the reaction, it is neces-
sary to know the behavior of the reagents in solution, which will
allow us to determine the species present in the reaction me-
dium and their concentration.
N-Chlorosuccinimide in aqueous solution
Despite numerous studies on NCS, the exact value of its acidity
constant, and of other N-haloamines, is not known. It is known
that the pKa values of N-haloamines are about 10 units less than
the pKa of corresponding amines.[43] So, taking this into account
and given that the value of the acidity constant of succinimide is
K = 1.95ꢃ 10ꢀ10 [44]
,
the value of the acidity constant for the NCS
will probably be less than zero.
On the other hand, we found a theoretical value for the pKa of
NCS, pKa = (ꢀ2.78 0.02) that has been calculated using the
Advanced Chemistry Development (ACD/Labs) Software V8.14.
If this value is considered, the predominant species in aqueous
solution is the neutral NCS, in all the ranges of pH in which this
study was carried out.
Figure 4. Influence of pH on kobs in the formation reaction of
N-chlorobenzylamine. [Buffer]T = 0,1 M.
[Benzylamine] = 10ꢃ [NCS],
(●) H2PO4 –/HPO4 2–, (▲) H3BO3/H2BO3 –, (■) HPO4 2–/PO4
3–
The NCS solutions were prepared in acetonitrile to avoid
contact with water and thus avoid the possible processes of hy-
drolysis that give rise to the formation of HOCl or ClO–. When the
reaction mixture occurs, and the NCS is in contact with water, an
equilibrium acid–basic between the free NCS and the proton-
ated NCS can take place. These processes are very fast, faster
than the reactions which will be studied. As a result, in the range
of pH studied, all the NCS is going to be an unprotonated form of
the species.
value, which is independent of pH. The slope of this relationship
is close to unity at pH < 9, so the exponent at which the proton
concentration in the rate equation is elevated is c ≈ ꢀ1 (Eqn 4). In
an alkaline medium, at pH > 10, the results do not fit this
equation, revealing a more complex relationship between kobs
and pH.
Furthermore, the influence of a buffer solution concentration
of phosphate acid (pKa = 6.8) on the rate constant was also stud-
ied for this chlorination reaction. In this study, the values of the
rate constant increase slightly, while increasing the buffer
concentration, when the concentrations of NCS and benzy-
lamine are kept constant. This variation in the rate constant, of
approximately 10%, can be justified on the basis of a slight in-
crease in pH that occurs by varying the concentration of the
buffer solution.
2,2,2-Trifluoroethylamine in aqueous solution
2,2,2-Trifluoroethylamine is a weak base. In the literature, we
have found values between 5.4 and 5.7 for the pKa value of the
protonated amine in aqueous solution.[45–48] In the present work,
we consider the value of pKa = 5.70 because it is the most
referenced value found.
The influence of the ionic strength (I) on the rate constant was
also studied. In this series of experiments, only the ionic strength
was modified in each test, using different NaClO4 concentrations.
The results show that the modification of the ionic strength
causes a substantial variation in the pH of the medium. The
variation observed in the value of the rate constants is almost ex-
clusively attributable to the variation of pH.
On the other hand, a study of the influence of temperature on
the rate constant was carried out at 15, 25, 35, and 45 °C. The
results show an increase of the rate constant with increasing
temperature. These experimental results are in compliance with
According to this value and considering the range of pH in
which this study was carried out, pH = 4–7, the predominant spe-
cies will be the free amine when pH > pKa or the protonated
amine when pH < pKa. Therefore, these two species must be
considered to propose the reaction mechanism.
Benzylamine in aqueous solution
Benzylamine is a weak base. In the literature, the values for the ion-
ization constant of this amine were found between 9.34–9.60 at
25 °C.[49–52] In the present work, we consider the value of
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J. Phys. Org. Chem. 2014, 27 407–418

DETERMINATION OF SECOND-ORDER RATE CONSTANTS
pKa = 9.37. Therefore, in aqueous solution, both species, R1NH2 and
R1NH+3, coexist in appreciable amounts in a pH range between 8.5
and 10.5. The predominant species is the protonated benzylamine
at pH < 8.5, while the free benzylamine is the predominant specie
at pH > 10.5.
Formation of N-chloramines
In the literature, we found two hypothetical mechanisms that
allow us to explain the transfer of Cl+ between the nitrogenous
centers of both species.[53,54] One of them proposes a mecha-
nism in which the hydrolysis of NCS takes place in the determin-
ing step of the rate reaction. In this step, the HOCl is formed and
reacts with the amine to give the corresponding N-chloramine.
Therefore, the reaction rate would be independent of the amine
concentration or of its nature.
Scheme 2. Reaction mechanism proposed for the formation reaction of
N-chloro-2,2,2-trifluoroethylamine
In the other proposed mechanism, there is a direct transfer of
Cl+ from the halogenating agent to the other species. In this
case, the rate reaction for the chlorinating of the amine depends
on the amine concentration.
The results obtained in this study suggest that the reactions
can be justified in accordance with this second mechanism of re-
action, because a dependence of the apparent rate constant on
the amine concentration was found when the pH of the medium
is constant.
When the experiments were carried out using different con-
centrations of an external buffer solution, either phosphate or
acetate, it was found that the reaction rate increases when the
concentration of the buffer solution increases, without modify-
ing the pH of the medium. Consequently, this must be attributed
to the influence of the concentrations of these species on the re-
action rate.
Therefore, it will also be necessary to consider this when
proposing a more complete reaction mechanism. One step
(Scheme 3), in which the species used in the preparation of the
buffer solution also participate, must be included in the afore-
mentioned mechanism.
Reaction mechanism for the formation of N-chloro-2,2,2-
trifluoroethylamine
As a result, the expression for the reaction rate should also in-
clude a sum of terms corresponding to the catalytic steps.
Considering the previously mentioned texts, it is necessary to
propose four possible steps in order to justify the reaction
mechanism. These are the result of the combination of the two
possible species of amine and the two possible species of the
chlorinating agent that are present.
In accordance with this, and comparing the experimental re-
sults with the theoretical representations deduced from the four
possible steps proposed, we can deduce that only one of them is
possible: the reaction between the free NCS and the
unprotonated amine. This is the determining step of the rate re-
action that allows us to justify the results obtained in the pH
range 4–7. Therefore, the reaction mechanism involves the fol-
lowing steps (Scheme 2).
d½R1NHClꢁ
v2 ¼
dt
Â
Ã
¼ k2 ½R1NH2ꢁ ½NCSꢁ þ ∑ kHA HAi ½R1NH2ꢁ ½NCSꢁ
(8)
i
i
Thus, the calculation of the rate-catalytic constants could be
performed by designing a set of experiments in which the cata-
lyst concentration is modified. In the present work, not enough
studies have been performed to allow us to calculate these cat-
alytic constants, as this was not the main objective.
Assuming that the ionization equilibriums are very fast, the rate
equation for the formation of N-chloro-2,2,2-trifluoroethylamine
deduced from this mechanism can be written as:
Reaction mechanism for the formation of N-chlorobenzylamine
When the aqueous solutions of benzylamine and NCS are mixed,
two different species of NCS and two different species of
benzylamine can be in the medium of the reaction. Therefore,
as in the previous kinetic study to justify the reaction mechanism
of the formation of N-chloro-2,2,2-trifluoroethylamine, it is neces-
sary to propose four possible steps because of the combination
of the four species present in the medium.
d½R1NHClꢁ
v2 ¼
¼ k2 ꢃ ½R1NH2ꢁ ꢃ ½NCSꢁ
(5)
dt
The concentrations of R1R2NH and NCS can be expressed in
terms of the total concentrations, [Am]T and [NCS]T, respectively:
Comparing the experimental results with the theoretical
representations obtained, for each of the possible steps, we
can deduce that only one of these steps reproduces the experi-
mental results. The chlorinating reaction occurs through the
K2
K1
v2 ¼ k2 ꢃ ½AmꢁT ꢃ
ꢃ ½NCSꢁT ꢃ
(6)
(7)
K2 þ ½H3Oþꢁ
K1 þ ½H3Oþꢁ
K2
K1
kobs ¼ k2 ꢃ ½AmꢁT ꢃ
ꢃ
K2 þ ½H3Oþꢁ K1 þ ½H3Oþꢁ
The rate constant is calculated by using a nonlinear fit of the
experimental results. The value obtained, k2 = (6.8 0.2) Mꢀ1 sꢀ1
suitably reproduces the results obtained.
,
Scheme 3. Catalytic step for the reaction of 2,2,2-trifluoroethylamine
with N-chlorosuccinimide (NCS)
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C. PASTORIZA ET AL.
reaction between the neutral species of NCS and of amine. In ac-
cordance with this reaction mechanism (Scheme 4), the reaction
rate increases with increasing the pH of the medium until a pH
value equal to the pKa of benzylamine is reached.
Assuming that the acid–base equilibriums are faster than the
transfer process of chlorine (Eqn 5) and performing a mathemat-
ical development as in the previous reaction, we can calculate
the rate constant by fitting the experimental results to this equa-
tion deduced from the proposed mechanism (Eqn 7).
The same behavior was observed for the reaction of 4-
methylbenzylamine with NCS. The values of the rate constants
were k2 = (4.3 0.5)ꢃ 105 Mꢀ1 sꢀ1 and k2 = (5.0 0.3)ꢃ 105 Mꢀ1 sꢀ1
for both reactions, respectively.
To sum it up, the reactions studied in the present work takes
place by a mechanism involving transfer of Cl+ from NCS to
the amino compound. These reactions of chlorine transfer are a
kind of nucleophilic substitution reactions in which occurs the
transfer of a cation such as NO+,[55–57] Br+[58] to a nitrogenous
compound with amino group.
studies were carried out to in the gas and aqueous phase. All
calculations were performed with Gaussian 03.[63] The geome-
try of each stationary point was optimized at the density
functional theory level with the 6–31 + G* basis set (calculations
with a bigger basis set were performed for some structures in
order to test the results). Becke’s three-parameter exchange
functional (B3)[64] was employed in conjunction with the
Lee–Yang–Parr correlation functional (LYP).[65]All points were
confirmed as minima or transition states by calculating the
harmonic vibrational frequencies using analytical second
derivatives. In addition, the path for the reaction was obtained
using the intrinsic reaction coordinate[66] at the same theoreti-
cal level. Solvation effects were included with polarizable
continuum model.
The transition states for the hydrolysis of NCS and the pro-
posed concerted reaction were located (Scheme 5). The differ-
ence between the energy barriers for these processes support
the concerted mechanism: The energy barrier for this mecha-
nism is 45.4 kcal molꢀ1 and for the hydrolysis is 65.3 kcal molꢀ1
.
There are few theoretical studies on the mechanism for N-
chlorination reactions of amino compounds with NCS.[59] However,
there are theoretical studies of the reaction of these nitrogenous
compounds with HOCl[60–62] In this case, both kinetic studies and
theoretical studies suggest that the reaction takes place via a con-
certed mechanism, in which the N atom of the amino compound
attacks on the Cl atom of the HOCl. The transition state proposed
is a cyclic structure assisted by at least one water molecule.
In order to propose a possible transition state structure for the
N-chlorination reaction of benzylamine by NCS, computational
The presence of solvent, simulated by PCM//B3LYP/6–31 + G*
computations, seems not significantly affect the energetic of
the process.
DISCUSSION
Kinetic studies carried out in the present work show that the
chlorination reactions of amines with NCS are oxidation pro-
cesses, in which the molecule with a Cl+ atom acts as an oxidant.
The bibliographic information available, as well as that obtained
in our studies, allows us to establish that these reac-
tions occur through two perfectly distinguishable steps
with very different rates: an initial fast process of forma-
tion of a N-haloamine followed by a slower decomposi-
tion process of the same, according to Scheme 1.
In the particular case of the reaction of NCS with
benzylamine, the ammonia and benzaldehyde were
identified as final products of the reaction.[23]
These two processes occur with a very different half-
time. So it is possible to design an experimental
method whereby we can independently determine
the constants kf and kd.
Iodometric method
A study of the reaction was performed using an
iodometric method. The N-chloramines react with po-
tassium iodide in acidic medium, liberating iodine. On
the basis of this property, the N-chloramine concentra-
tion was determined from the liberated iodine that was
Scheme 4. Reaction mechanism proposed for the reaction formation of
N-chlorobenzylamine with NCS
Scheme 5. Optimized geometries of the transition states for (a) formation of N-chlorobenzylamine with N-chlorosuccinimide (NCS) and (b) NCS
hydrolysis
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J. Phys. Org. Chem. 2014, 27 407–418

DETERMINATION OF SECOND-ORDER RATE CONSTANTS
titrated with a thiosulfate solution, using starch solution as indica-
tor. This method determines the total Cl+ existing in the medium
of reaction, regardless of where the Cl+ is found.
According to this study, it was found that the decomposition re-
action of the N-chlorobenzylamine follows a first-order kinetic. The
rate constant, for this reaction of decomposition, was obtained
using three different concentrations of NCS in acidic medium.
The value obtained is kd = (2.08 0.09)ꢃ 10ꢀ5 Mꢀ1 sꢀ1 and
t1/2 = 9.26h. This value is in accordance with the value obtained
for the decomposition reaction of the N-chlorobenzylamine formed
in the reaction of benzylamine with HOCl (kd = (2.40 0.03)ꢃ
10ꢀ5 Mꢀ1 sꢀ1 and t1/2 = 8.02 h). This reaction has also been
studied in this work, under the same experimental conditions.
This indicates that the product obtained in the chlorinating re-
actions of benzylamine using NCS and HOCl is the same.
Moreover, the value obtained iodometrically represents the
disappearance rate of Cl+ of the reaction medium, that is, the
decomposition rate of the N-chlorobenzylamine formed. This
value is very small compared with the kinetic constants for the
N-chlorobenzylamine formation, indicating that the decomposi-
tion process does not interfere with the formation process of this
N-chloramine, and therefore, they can be studied independently.
The available literature regarding the decomposition pro-
cesses is quite extensive, so we have not delved more into the
study of the decomposition of N-chlorobenzylamine. These ex-
periments were carried out in acid medium because according
to the literature, these decompositions occur with moderate
rates in strongly basic mediums; while in weak acid or basic
mediums, these processes are slower. Figure 5 shows some
results obtained in the study of decomposition reactions with
N-chloramines, using a wide range of pH, that allow us to see
the general behavior in these systems.
Figure 5. Dependence of the rate constant in the decomposition
process of N-chloramines with pH at 25 °C. (▲) N-chloro-2-amino-1-
butanol,[46] (○) N-chloro-2-amino-2-methyl-1-propanol,[46] (●) N-chloro-
sec-butylamine,[27] (□) N-chlorobenzylamine,[45] (∇) N-chlorobenzylamine
(15 °C),[45] (▼) N-chlorobenzylamine (this work), (Δ) N-chlorobenzylamine
(this work)
Hussain et al.[67] studied the hydrolysis rate of chlorinated mol-
ecules, including NCS. They estimated the rate constant for this
process from the constant for the hydrolysis equilibrium and
from the rate constant for the formation process of the N-chloro
compound. These studies were performed spectrophotometri-
cally, in isolation conditions ([NCS] > [HOCl]) and in the presence
of a CH3COOH/CH3COO– solution. According to the experimental
results, these authors proposed a reaction mechanism in which
the attack of the OH– ion on the NCS takes place in the rate de-
termining step. The rate constant obtained for this process was
Spectrophotometric method
In the present work, the monitoring of the reaction was carried
out using a spectrophotometric method with a stopped-flow
spectrophotometer, which allows us to study fast reactions with
a half-time of milliseconds.
A previous spectrophotometric study was performed to demon-
strate that when the reaction mixture occurs there is a substantial
increase in the absorbance, with respect to the absorbencies of
the reagents separately. This absorption band corresponds to the
N-chloramine formed and slowly decreases with time.
9.80ꢃ 103 Mꢀ1 sꢀ1
.
In their work, the authors compared this value to those
obtained for the reactions of nitrogenous compounds with
NCS, reactions in which there is a direct transfer of Cl+ from
the NCS to another nitrogenous compound. The study allowed
them to conclude that the hydrolysis rate of the N-chlorinated
compounds studied is slower than the transfer rate of active
chlorine to nitrogenous bases in water. The Cl+ transfer occurs
as a result of a direct reaction between a basic receptor molecule
and the N-chlorinated molecule.
This behavior is typical of all reactions in which there is a
t
compound that contains an atom of Cl+: HOCl, ClO–, BuOCl,
To verify the value of the hydrolysis constant, a spectrophoto-
metric study was performed measuring the absorbance corre-
sponding to the maximum absorption of the ClO– ion at
292 nm. A set of experiments was carried out in alkaline medium
at 25 °C, ionic strength 0.5 M, with [NCS] = 5ꢃ 10ꢀ4 M and in ex-
cess of OH– ion, with a [OH–]/[NCS] mole ratio higher than 10.
The results confirm that the reaction is first order with respect
to [NCS] and [OH–]. The second-rate constant obtained for the
NCS, NCNMPT, CAT, CAB… All of them react with the com-
pounds that have an amino group (R1R2NH) to form the corre-
sponding N-chloramine (R1R2NCl). The N-chloramines can
present absorption bands between 240–270 nm that subse-
quently decompose very slowly.
In addition to this, the influence of the hydrolysis process of
the NCS reagent on the rate of the chlorination reaction of amino
compounds must be also considered in this discussion.
hydrolysis reaction of the NCS is kh = (1.27 0.05)ꢃ 104 Mꢀ1 sꢀ1
.
This result is concordant with the literature.
In the study of the reaction of NCS with 2,2,2-trifluoro-
ethylamine and benzylamine, the solutions of NCS were pre-
pared in acetonitrile to avoid its hydrolysis, so the NCS will only
be in contact with water at the time of the reaction mixture.
The hydrolysis process is slower than the chlorination process
of amines, so it does not noticeably interfere in the kinetic
study of the formation reaction of N-chloramines. Moreover, a
Hydrolysis of N-chlorosuccinimide
In aqueous solution, the NCS undergoes a hydrolysis process
whose kinetic was studied by different researchers, verifying that
the formation rate of HOCl or ClO– is much slower than the
formation rate of N-chloramines, in the reactions of amines
with NCS.
J. Phys. Org. Chem. 2014, 27 407–418
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C. PASTORIZA ET AL.
system of asymmetric mixture (1 : 25) was used to minimize the
effect of a nonaqueous solvent. This system allowed us to mix
a volume of NCS solution in acetonitrile with 25 volume of the
amines solution in water.
Under the experimental conditions used to carry out this
kinetic study, the Cl+ transfer occurs from the NCS to amino
group of the amines. The inverse process could also occur, but
this process does not affect the calculation of the rate constants
of formation of the N-chloro-2,2,2-trifluoroethylamine and of the
N-chlorobenzylamine under these experimental conditions.[9,22]
In the plot of log k against pKa (Fig. 6, Table 2), we can observe
a little difference in the behavior of the nitrogenous compounds
possessing a primary amino group (R1NH2, R2 = H) to those
possessing a secondary amino group (R1R2NH). Furthermore,
we can see that the order of magnitude of the values of the rate
constants obtained in the present work are in accordance with
the tendency of the values found in the literature for other ni-
trogenous compounds.
Moreover, the slope values, resulting from the adjustment by
least squares, correspond to the term α in accordance with the
Brönsted equation. In both cases, these values are close to 1,
which indicate that the transition state is close to the products
Free-energy relationships
Despite the fact that NCS is a compound whose power of chlori-
nation has been known for many years, in the literature, we have
found very few kinetic studies of the chlorination of nitrogenous
compounds possessing an amino group, either primary (R1NH2)
or secondary (R1R2NH). The values found along with the values
obtained in the present work for both amines are included in
Table 2.
These values can be used to establish some structure–reactiv-
ity relationships such as the Brönsted equation, Taft equation,
and the relationships of Swain–Scott and Ritchie. These relations
of free energy will allow us to clarify the reaction mechanism of
the reactions studied in the present work.
Brönsted equation
This relation allows us to quantify the free energy of a process
through experimental parameters, in our case with the rate con-
stant for the formation reaction of N-chloramines.
log k ¼ ꢀα pK þ c
(9)
Figure 6. Brönsted relationship, log k versus pKa. (●) R1NH2, (○) R1R2NH.
(1–2,2,2-trifluoroethylamine, 2-morfoline, 3-diethanolamine, 4-benzylamine,
5-ethylethanolamine, 6-glycine, 7-methylethanolamine, 8-2-methylalanine,
9-sarcosine, 10-proline, 11-dimethylamine, 12-diethylamine, 13-pyperidine,
14-pyrrolidine)
This relation gives us an idea of the energy change corre-
sponding to the state of transition relating to the reagents, with
the change of the dissociation constant of nitrogenous com-
pound dissociation that the Cl+ is going to transfer.
Table 2. Rate constants and structural parameters for the reaction of nitrogenous compounds with N-chlorosuccinimide
Nitrogenous compound
pKa
kNCS/Mꢀ1 sꢀ1
Σσ*[68,69]
n
N+
Ref.
c
2,2,2-Trifluoroethylamine
Morpholine
Diethanolamine
Benzylamine
Ehtylethanolamine
Glycine
Methylethanolamine
2-Methylalanine
Sarcosine
5.7
8.55
8.96
9.37
9.48
9.68
9.9
10.10
10.20
10.65
10.78
6.8
1.90
1.16
0.89
1.20
0.59
0.92
0.69
1.00a
0.60a
0.46a
0.49
0.49
0.29
0.35
0.23
4.08
5.16
4.94b
5.04
4.82
5.11
5.38
3.45
7.14
6.34
6.20
5.96
6.51
7.40
4.0ꢃ105
9.8ꢃ104
4.3ꢃ105
1.5ꢃ106
6.3ꢃ105
3.9ꢃ106
1.29ꢃ106
2.09ꢃ106
5.7ꢃ106
1.5ꢃ107
4.1ꢃ107
4.6ꢃ107
4.3ꢃ107
1.55ꢃ107
[10]
[11]
c
[11]
[9]
[11]
[9]
5.40b
5.41b
5.83
5.83
5.20
5.67
5.02
7.51
7.53
7.95
7.95
6.85
7.92
8.11
Proline
Dimethylamine
[10]
[11]
[11]
[10]
[9]
Diethylamine
Piperidine
Pyrrolidine
11.02
11.12
11.22
aCalculated by Hall’s equations: pKa = 13.23 ꢀ 3.14 Σσ * and pKa = 12.13 - 3.23 Σσ *, for primary and secondary amines,
respectively.[70]
bCalculated by the linear relation: N+ = (- 6 1) + (2.5 0.2)n.
cObtained in this work.
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DETERMINATION OF SECOND-ORDER RATE CONSTANTS
state (α = 1.23 0.06 and α = 0.9 0.1 for R1NH2 and R1R2NH,
respectively).
and s represents the susceptibility of the electrophile versus the
nucleophile substitution.
log k ¼ s n þ constant
(11)
Taft equation
The Taft relation allows us to characterize the polar effects of the
reaction through the rate constant and one parameter, σ*,
denominated Taft’s parameter, which is characteristic of the sub-
stituent. This parameter is a measure of the ability of the substit-
uent to attract electrons.
In the Ritchie equation, the characteristic parameter of the nu-
cleophile, N+ is a measure of some important physical property,
intrinsic to the nucleophile.
log k ¼ Nþ þ constant
(12)
k
ꢄ
log
¼ ρ Σσ
(10)
kMe
The literature values available for n and N+, nucleophile
parameters, for each of nitrogenous compounds are listed in
This relationship was used as a starting point to establish a re-
lationship between the pKa of the nitrogenous compounds and
the Taft’s parameter, σ*. This correlation has been established
for numerous nitrogenous compounds by Hall,[70] who found a
linear different relation depending on the amino group that pos-
sesses the nitrogenous compound.
These relationships are very useful to determine the value of
the Taft parameter of one substituent, if the literature value is
not available, from the pKa value of the nitrogenous compound.
In the present work, the values of Σσ* were calculated for
2-methylalanine, sarcosine, and proline. The values obtained
are also listed in Table 2.
The Taft representation, log k versus Σσ* for all nitrogenous
compounds (Table 2) is shown in Fig. 7. The value obtained for
the slope, ρ = ꢀ3.5 0.4, indicates that this chlorination reaction
of nitrogenous compounds with NCS is very sensitive to the
polarity of the substituents.
Swain–Scott and Ritchie equations
Figure 8. Swain–Scott representation, log k versus n. (●) R1NH2, (○)
R1R2NH. (1–2,2,2-trifluoroethylamine, 2-morfoline, 3-diethanolamine,
4-benzylamine, 5-ethylethanolamine, 6-glycine, 7-methylethanolamine, 9-
sarcosine, 10-proline, 11-dimethylamine, 12-diethylamine, 13-pyperidine,
14-pyirrolidine)
These free-energy relations reflect the nucleophile character of
the nitrogenous compound. In the Swain–Scott equation, the
parameter n represents the nucleophile character of the amine
Figure 7. Taft representation, log k versus Σσ*. (●) R1NH2, (○) R1R2NH.
(1–2,2,2-trifluoroethylamine, 2-morfoline, 3-diethanolamine, 4-benzylamine,
5-ethylethanolamine, 6-glycine, 7-methylethanolamine, 8-2-methylalanine,
9-sarcosine, 10-proline, 11-dimethylamine, 12-diethylamine, 13-pyperidine,
14-pyirrolidine)
Figure 9. Ritchie representation, log k versus N+.(●) R1NH2, (○) R1R2NH.
(1–2,2,2-trifluoroethylamine, 2-morfoline, 3-diethanolamine, 4-benzylamine,
5-ethylethanolamine, 6-glycine, 7-methylethanolamine, 9-sarcosine, 10-pro-
line, 11-dimethylamine, 12-diethylamine, 13-pyperidine, 14-pyrrolidine)
J. Phys. Org. Chem. 2014, 27 407–418
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C. PASTORIZA ET AL.
Table 2. As can be seen in this table, there is no value for these
two parameters for 2-methylalanine. However, for other com-
pounds such as diethanolamine, sarcosine, and proline, only
one of them was found. In these cases, we can calculate the
unknown parameter from the linear expression obtained by
the adjustment of least squares in the representation of N+ ver-
sus n. The values obtained are included in Table 2.
The good linear relation obtained in this representation, N+
versus n, justifies the existence of a correlation among these
nucleophile parameters. The positive slope indicates that the re-
action rate of these nitrogenous compounds for the reactions of
the nucleophilic addition (Ritchie relationship) is significantly
greater than the reactions of the nucleophilic substitution
(Swain–Scott relationship).
ture values come from different studies, with the exception of
the two values obtained in the present work.
The slope obtained by least squares fit, in the Swain–Scott rep-
resentation (Fig. 8), is s = 3.3 0.6. However, this value is greater
than the value estimated by Swain–Scott for nucleophilic reac-
tions with nitrogenous compounds that possess an amino group
(s = 0.6 – 1.2). This is because the values are defined for the reac-
tions in which the nucleophilic attack occurs on a carbon atom
and not on a chlorine atom.
Despite this, the existence of a good linear relation allows us
to consider the s value as an additional criterion of the participa-
tion of the nucleophile in the transition state, that is, the differ-
ence in the slope value for the substitution reaction of the
chlorine atom, s = 3.3 0.6, compared with the value that would
be expected, s = 0.6 – 1.2, indicates the ability to form the bond
between the Cl and the nucleophile in the transition state com-
paring it with the formation of the bond with the carbon atom
for which the parameters n are defined.[71]
The representations in accordance with the Swain–Scott and
Ritchie relationships are shown in Figs 8 and 9. In both cases, de-
spite the observed dispersion in the values that are represented,
good linearity can be seen. This dispersion is because the litera-
Table 3. Second-order rate constants for N-chlorination of nitrogenous compounds with different chlorinating agents
Nitrogenous compound
k/Mꢀ1 sꢀ1
NCS
pKa
HOCl
NCNMPT[25]
2,2,2-Trifluoroethylamine
5.70
8.55
8.6ꢃ106a
4.5ꢃ107a
6.8
0.08
Morpholine
4.0ꢃ105[10]
2.4ꢃ103
Benzylamine
Glycine
9.37
9.68
1.0ꢃ108[24]
4.3ꢃ105
3.6ꢃ103
1.4ꢃ103
10ꢃ104
1.2ꢃ106
5ꢃ107[72]
6.3ꢃ105[9]
11.3ꢃ107[73]
Dimethylamine
Piperidine
10.78
11.12
5.0ꢃ108[74]
9.8ꢃ107[75]
6.05ꢃ107[76]
1.5ꢃ107[10]
4.1ꢃ107[11]
10.8ꢃ107a
4.3ꢃ107[10]
aExtrapolated value from Taft relationship of amino compounds[77] log k = 8.2 0.5Σσ *.
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J. Phys. Org. Chem. 2014, 27 407–418

DETERMINATION OF SECOND-ORDER RATE CONSTANTS
In the case of the Ritchie representation (Fig. 9), the slope
obtained by least squares fit, 1.3 0.2, is in accordance with the
theoretical value. This means that the formation reactions of
N-chloro compounds with NCS studied are type SN2 and occur
through a concerted mechanism.
REFERENCES
[1] P. Kovacic, M. K. Lowery, K. W. Field, Chem. Rev., 1970, 639.
[2] J. C. Guillemin, J. M. Denis, Angew. Chem. Int. Ed. Engl., 1982, 21, 690.
[3] Y.-L. Zhong, H. Zhou, D. R. Gauthier, J. Lee, D. Askin, A. H. Dolling,
P. R. Volante, Tetrahedron Lett., 2005, 46(7), 1099.
[4] Z. Wang, L. Zhu, F. Yin Z. Su, Z. Li, C. Li, J. Am. Chem. Soc., 2012,
134(9), 4258.
The values obtained in the present work, for the formation
rates of the N-chloramines from the reaction of the NCS with
benzylamine and 2,2,2.trifluoroethylamine are summarized in
the Table 2, along with other values available in literature. A
good linearity between all values listed in this table was found
for all free-energy relationships considered. The good agreement
of these values in these representations allows us to justify the
reaction mechanism proposed, despite the fact that all the
values considered for these relationships were taken from
different sources. All of them correspond to kinetic studies of
the chlorination reaction of nitrogenous compounds that pos-
sess an amino group with NCS. In these reactions, there is a di-
rect transfer of Cl+ from the NCS to the nitrogenous compound.
[5] B. S. Moodithaya, B. Thimme Gowda, J. Indian Chem. Soc., 2002,
79, 420.
[6] V. Girardon, M. Tessier, E. Marechal, Polymer Bull., 1994, 33(6), 657.
[7] K. Sreekumar, V. N. Raajasekharan Pillai, Polymer, 1987, 28(9), 1599.
[8] M. Deborde, U. von Gunten, Water Res., 2008; 42(1–2), 13.
[9] J. M. Antelo, F. Arce, J. Crugeiras, M. Parajó, J. Phys. Org. Chem., 1997,
10, 631.
[10] T. Higuchi, A. Hussain, I. H. Pitman, J. Chem. Soc. B., 1969, 626.
[11] J. M. Antelo, F. Arce, J. Franco, M. C. Garcia Lopez, M. Sanchez, A.
Varela, Int. J. Chem. Kinet., 1988, 20, 397.
[12] M. M. Campbell, G. Johnson, Chem. Rev., 1978, 78(1), 65.
[13] B. T. Gowda, D. S. Mahadevappa, J. Chem. Soc. Perkins Trans. 2, 1983,
323.
[14] B. T. Gowda, M. Shetty, J. Phys. Org. Chem., 2004, 17, 848.
[15] M. K. Veeraiah, A. S. Ananda Murhty, N. M. Made Gowda, Synth.
React. Inorg. Met. Org. Nano-Met. Chem., 2010, 40, 225.
[16] F. D. Chattaway, O. G. Backeberg, J. Chem. Soc., 1923, 123, 2999.
[17] F. D. Chattaway, O. G. Backeberg, J. Chem. Soc., 1924, 125, 1097.
[18] M. Zimmer, L. F. Audrieth, J. Am. Chem. Soc., 1954, 76, 3856.
[19] M. Anbar, I. Dostrovsky, J. Chem. Soc., 1954, 1094.
[20] Y.-L. Zhong, P. G. Bulger, S. G. Newman, M. Lautens, Org. Synth.,
2010, 87, 8.
Effectiveness of different N-chlorinating agents
For comparison, the effectiveness of different N-chlorinating
agents, we have summarized in Table 3 the rate constants values
to chlorination reactions of nitrogenous compounds with pri-
mary and secondary amino group, with different chlorinating
agents: HOCl, NCS, and N-chloro-N-methyl-p-toluenensulfona-
mide (NCNMPT). All of them contain one electrophile chlorine
atom, able to react with the amino group of nitrogenous com-
pound to form the N-chloramine.
In this table, the rate constants values of 2,2,2-trifluoroethy-
lamine and benzylamine with NCS obtained in the present work
were included, and the values to other amino compound
obtained by the research group where these studies were
carried out. Also, other values from literature are included to
compare the effectiveness in chlorination processes.
For the same nitrogenous compound, the reactivity order with
respect to the chlorinating agent is k(HOCl)>k(NCS)>k
(NCNMPT). It is important take into account that the rate at
which the N-chlorination reaction occurs, with each one chlori-
nating agents, depends not only on the rate constant but also
of its dependence with pH. This is necessary to consider for the
determination of the rate of these reactions at a pH given.
[21] Y. Chen, L. Wang, H Y., Q. Shi, X. Dong, J. Mater. Sci., 2007, 42(11),
4018.
[22] V. Benin, P. Kaszynski, J. G. Radziszewski, Tetrahedron, 2002, 58(11),
2085.
[23] K. K. Banerji, J. Chem. Soc. Perkin Trans 2, 1988, 1015.
[24] J. M. Antelo, F. Arce, J. Crugeiras, C. Pastoriza, A. Rios, J. Chem. Res.
(S), 2001, 20.
[25] C. Pastoriza, J. M. Antelo, J. Crugeiras, J. Phys. Org. Chem., 2013,
26(7), 551.
[26] W. A. Weaver, J. Li, Y. Wen, J. Johnston, M. R. Blatchey, E. R. Blatchey
III, Water Res., 2009, 43, 3308
[27] S. Bosillon, M. Lemasle, E. Renault, D. Toza, V. Heim, A. Laplanche,
Chemosphere, 2009, 77, 1035.
[28] M. Huerta-Fontela, M. T. Galceran, F. Ventura, Water Res., 2011,
45, 1432.
[29] S. K. Khetan, T. J. Collins, Chem. Rev., 2007, 107, 2319.
[30] M. D. Rees, C. L. Hawkins, M. J. Davies, J. Am. Chem. Soc., 2003,
125, 13719.
[31] L. A. Paquette, Encyclopedia of Reagents for Organic Synthesis, Vol. 2,
(Ed: L. A. Paquette), John Wiley & Sons, New York, 1955, 1205.
[32] D. A. Skoog, D. M. West, Química Analítica, Ed. McGraw-Hill, Madrid,
4 edn, 1989.
[33] R. S. Treptow, J. Chem. Ed., 1998, 75(8), 992.
[34] J. Andraos, J. Chem. Ed., 1996, 73(2), 150.
CONCLUSIONS
[35] N. R. Draper, H. Smith, Applied Regression Analysis, 3rd edn, John
Wiley & Sons, New York, 1998.
[36] J. M. Antelo, F. Arce, M. C. Castro, J. Crugeiras, J. C. Pérez-Moure, P.
Rodríguez, Int. Chem. Kinet., 1995, 27, 703.
[37] J. M. Antelo, F. Arce, M. Parajó, J. Phys. Org. Chem., 1996, 9, 447.
[38] J. M. Antelo, F. Arce, D. Casal, P. Rodríguez, A. Varela, Tetrahedron,
1989, 45, 3955.
[39] J. M. Antelo, F. Arce, J. Casado, E. Novoa, M. E. Sánchez, A. Varela, An.
Quim., 1987, 83, 589.
[40] M. P. Synder, D. W. Margerum, Inorg. Chem., 1982, 21, 2545.
[41] M. Ferriol, J. Gazet, M. T. Saugier-Cohen Adad, Int. J. Chem. Kinet.,
1991, 23, 315.
[42] J. M. Antelo, F. Arce, M. Parajo, Int. J. Chem. Kinet., 1995, 27, 637.
[43] J. M. Antelo, F. Arce, M. Sánchez, A. Varela, Bull. Soc. Chim. Belg.,
1989, 98, 85.
[44] D. Matte, B. Solastiok, A. Merlin, X. Deglise, Can. J. Chem., 1992, 70,
89.
[45] R. Kluger, J. C. Hunt, J. Am. Chem. Soc., 1984, 106(19), 5667.
[46] W. P. Jencks, J. Regenstein, Handbook of Biochemistry, 2nd edn (Ed:
H. A. Soper) Chemical Rubber Co., Cleveland, OH, 1970.
[47] P. G. Seybold, Int. J. Quant. Chem., 2008, 108, 2849.
It is known that NCS is a good reagent for electrophilic substitu-
tion reactions and for the addition of chlorine to organic com-
pounds. In the literature, there are some discrepancies with
regard to the mechanism through which the chlorination reactions
with NCS occur. In the present work, we have studied the chlorina-
tion reactions of two nitrogenous compounds, benzylamine and
2,2,2-trifluoroethylamine. In both cases, there is a chlorine transfer
process, from NCS to nitrogenous compound.
This kinetic behavior is similar to that of other nitrogenous
compounds with NCS found in the literature. The reaction is first
order with respect to each of the reagents. The formation reac-
tion of N-chloramines and its decomposition can be studied sep-
arately, and under the experimental conditions used in these
studies, the hydrolysis process does not interfere with the chlori-
nation process. Moreover, the good structure–reactivity relation-
ships shown in the present work allow us to justify the proposed
reaction mechanism.
J. Phys. Org. Chem. 2014, 27 407–418
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C. PASTORIZA ET AL.
[48] M. J. Gregory, T. C. Bruice, J. Am. Chem. Soc., 1967, 89, 4400.
[49] J. Graton, C. Laurence, M. Berthelot, J. Yves Le Questel, F. Besseau,
E. D. Raczynska, J. Chem. Soc. Perkin Trans. 2, 1999, 997.
[50] A. E. Martell, R. M. Smith, Critical Stability Constants, Vol. 2, Plenum
Press, New York, 1975.
Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C.
Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B.
Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski,
B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L.
Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C.
Gonzalez, J. A. Pople, Gaussian 03, Revision C.02, Gaussian, Inc.,
Wallingford CT, 2004.
[51] P. Petersson, T. Malmström, M. R. Euerby, Chromatographia, 2004,
59, 31
[52] W. H. Carothers, C. F. Bickford, G. J. Hurwitz, J. Am. Chem. Soc., 1927,
49(11), 2908.
[64] A. D. Becke, J. Chem. Phys. 1993, 98, 5648.
[53] T. Higuchi, J. Hasegawa, J. Phys. Chem., 1965, 69, 796.
[54] M. Ferriol, J. Gazet, R. Rizk-Ouaini, M. T. Saugier-Cohen Adad, Int. J.
Chem. Kinet., 1989, 28, 3808.
[65] C. Lee, W. Yang, R. J. Parr, Phys. Rev. B, 1988, 37, 785.
[66] C. Gonzalez, H. B. Schlegel, J. Phys. Chem. 1990, 94, 5223.
[67] A. Hussain, T. Higuchi, I. H. Pitman, J. Pharm. Sci. 1972, 61(3), 371.
[68] A. Willians, Free Energy Relationships in Organic and Bio-organic
Chemistry, The Royal Society of Chemistry, Cambridge, 2003.
[69] D. D. Perrin, B. Dempsey, E. P. Serjeant, pKa Prediction for Organic
Acids and Bases, Chapman & Hall, London, 1981.
[55] L. García-Río, J. R. Leis, J. A. Moreira, F. Norberto, J. Org. Chem. 2001,
66, 381.
[56] L. García-Río, E. Iglesias, J. R. Leis, M. E. Peña, A. Rios, J. Chem. Soc.
Perkin Trans. 2, 1993, 29
[57] Z. Sun, Y. D. Liu, R. Zhong, J. Mol. Model., 2011, 17:669–680
[58] M. Gazda, D. W. Margerum, Inorg. Chem. 1994, 33, 118.
[59] A. Akdag, M. L. McKee, S. D. Worley, J. Phys. Chem. A, 2006,
110, 7621.
[60] M. S. Rayson, M. Altarawneh, J. C. Mackie, E. M. Kennedy, B. Z.
Dlugogorski, J. Phys. Chem. A, 2010, 114, 2597.
[70] H. K. Hall, Jr., J. Am. Chem. Soc. 1957, 79, 5441.
[71] J. M. Antelo, J. Crugeiras, J. R. Leis, A. Rios, J. Chem. Soc. Perkin Trans.
2, 2000, 2071.
[72] D. W. Margerum, E. T. Gray, R. P. Huffman, ACS Symp. Ser. 1978, 82,
278.
[73] X. L. Armesto, M. Canle, J. A. Santaballa, Tetrahedron, 1993, 49, 275.
[74] I. Weil, J. C. Morris, J. Am. Chem. Soc., 1949, 71, 1664.
[75] D. Matte, B. Solastiouk, A. Merlin, X. Deglise, Can. J. Chem., 1989, 67,
786.
[61] J. Andrés, M. Canle L. M. V. García, L. F. Rodríguez Vázquez, J. A.
Santaballa, Chem. Phys. Lett., 2001, 342, 405.
[62] T. Tarade, V. Vrček, Int. J. Quant. Chem., 2013, 113, 881.
[63] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb,
J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C.
Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci,
M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada,
M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J.
B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W.
Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J.
[76] X. L. Armesto, M. Canle, M. V. García, M. Losada, J. A. Santaballa,
Tetrahedron, 1998, 54, 521.
[77] C. Pastoriza, Thesis. University of Santiago of Compostela, 2012.
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