Reactions of chlorination with tert-butyl hypochlorite (TBuOCl)

Article abstract of DOI:10.1002/poc.3377

The chlorination reactions of nitrogenous organic compounds (2,2,2-trifluoroethylamine, benzylamine, glycine, and dimethylamine) by tert-butyl hypochlorite (^tBuOCl) were studied at 25°C, ionic strength 0.5 M and under isolation conditions. The kinetic results obtained in the formation processes of the corresponding N-chloramines in acid medium (pH = 5-7) are summarized in this paper. Kinetic studies showed a first order with respect to ^tBuOCl concentration. The chlorination reactions involving benzylamine, glycine and dimethylamine were all first order with respect to nitrogenous compound concentration and approximately -1 order with respect to proton concentration. The reaction with 2,2,2-trifluoroethylamine was more complex, and the order of reaction with respect to the amine varied with pH.

Full text of DOI:10.1002/poc.3377

Research Article
Received: 25 April 2014,
Revised: 28 July 2014,
Accepted: 1 September 2014,
Published online in Wiley Online Library: 6 October 2014
(wileyonlinelibrary.com) DOI: 10.1002/poc.3377
Reactions of chlorination with tert-butyl
T
hypochlorite ( BuOCl)
Cristina Pastorizaa*, Juan Manuel Anteloa and Juan Crugeirasa
The chlorination reactions of nitrogenous organic compounds (2,2,2-trifluoroethylamine, benzylamine, glycine, and
dimethylamine) by tert-butyl hypochlorite (tBuOCl) were studied at 25 °C, ionic strength 0.5 M and under isolation conditions.
The kinetic results obtained in the formation processes of the corresponding N-chloramines in acid medium (pH = 5–7) are
t
summarized in this paper. Kinetic studies showed a first order with respect to BuOCl concentration. The chlorination reac-
tions involving benzylamine, glycine and dimethylamine were all first order with respect to nitrogenous compound concen-
tration and approximately ꢀ1 order with respect to proton concentration. The reaction with 2,2,2-trifluoroethylamine was
more complex, and the order of reaction with respect to the amine varied with pH. Copyright © 2014 John Wiley & Sons, Ltd.
Keywords: free-energy relationships; kinetics and mechanism; N-chloramines; N-chlorination; tert-butyl hypochlorite
chlorinating agents is interesting to compare because of the
INTRODUCTION
great importance of these N-chlorination reactions in environ-
mental and biochemical processes.[9,11,26–35]
N-chloro compounds are reagents frequently used in intermedi-
ate steps of synthesis of organic compounds.[1–7] The most com-
monly used reagents for the preparation of N-chloro compounds
include the following: sodium hypochlorite, N-chlorosuccinimide
EXPERIMENTAL METHOD
(NCS), chloramine-T, chloramine-B and tert-butyl hypochlorite
Reagents
(tBuOCl).[8–15] All of these contain a chlorine atom electrophile
The tBuOCl was obtained by passing a stream of chlorine through
a solution of NaOH, tert-butanol and water (Scheme 2).[36,37]
The product thus obtained was purified by distillation and
stored at 0 °C in a topaz flask, to avoid the decomposition by ac-
tion of light, and molecular sieves were added to absorb any wa-
(Cl+), which is able to react with amino groups (R1R2NH) of amino
acids, amines, amides and other nitrogenous compounds to
form the corresponding N-chloro compound. In these reactions,
an N–H bond breaking and formation of N–Cl bond take place.
The N–Cl confers oxidizing and bactericidal characteristics to
the N-chloro compounds, and therefore, some of them are used
directly as disinfectants or to develop new formulations for use
as bactericides.[16–18]
Tert-butyl hypochlorite is used as a reagent in the formation
process of N-chloramines with high yields.[23–25] The compound
can be prepared as a pure substance and can be stored for months
without undergoing appreciable deterioration.[19–22] Despite being
a dangerous product and more expensive than other chlorinating
agents, it is very useful for small scale research applications.
This paper summarizes the kinetic results obtained in the
study of the chlorination reactions of benzylamine, glycine,
dimethylamine and 2,2,2-trifluoroethylamine with tBuOCl to
form the corresponding N-chloramines (Scheme 1). These stud-
ies are particularly interesting because kinetic information about
the reactions of nitrogenous compounds with this chlorinating
agent (tBuOCl) has not hitherto been published.
This small group of nitrogenous compounds covers a large
pKa range (5.70–11.12). The values of the second-order rate con-
stants obtained allow us to justify a possible reaction mechanism
and establish structure–reactivity relationships. These relation-
ships were compared with others, which were established for
the reactions of these nitrogenous compounds with other chlo-
rinating agents: HOCl, NCS and N-chloro-N-methyl-p-
toluensulfonamide (NCNMPT). Moreover, these relationships
could also be used to predict the behavior of other nitrogenous
compound similar. Also, the effectiveness of the different N-
t
ter that may have been retained. The concentration of BuOCl
was determined iodometrically, thus verifying that the purity of
the product obtained was close to 100%. The solution used in ki-
t
netic experiments was prepared daily, from BuOCl synthesized
in the laboratory, using acetonitrile as solvent.
Aqueous solution of benzylamine, glycine, dimethylamine
chlorhidrate and 2,2,2-trifluoroethylamine chlorhidrate was pre-
pared using Aldrich commercial products quality p.a. grade. A buffer
solution of H3PO4/H2POꢀ4 was used to control the pH of the medium,
and a 2 M solution of NaClO4 was used to control the ionic strength.
Instrumental
Preliminary studies were performed using a spectrophotometer
Varian Cary 1Bio (Varian Cary 1 Bio, Middelburg, Netherlands) with
a thermostated cell holder equipped with quartz cells with 1 cm
path length and a capacity of 3 cm3. Reactions were monitored
using a stopped-flow spectrophotometer Applied Photophysics
DX.17MV (Applid Photophysics DX.17MV, leatherhead, UK) with a
* Correspondence to: C. 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 Santi-
ago de Compostela, 15782 La Coruña, Spain
J. Phys. Org. Chem. 2014, 27 952–959
Copyright © 2014 John Wiley & Sons, Ltd.

REACTIONS OF CHLORINATION
constant of decomposition for N-chloroglycine is kNCl = (4.3 0.7)
× 10ꢀ6 sꢀ1, t1/2 = 44.7 h, which is similar to the values reported
for other N-chloro amino acids.[38,39] The N-chloramines obtained
from aliphatic amines are more stable, increasing their decom-
position rate in acid mediums or strong basic.[40–43]
To select the most suitable conditions for kinetic monitoring of
the reaction, preliminary spectrophotometric studies of all reactants
and reaction mixture were carried out between 200 and 400 nm.
Analysis of the superposition of these spectra confirmed that, upon
mixing the reactants, the formation of N-chloro compounds occurs.
The N-chloro compounds present a typical band at 250 nm.
The spectrophotometric results allow us to determine the wave-
length in which there is a significant variation in absorbance, from
reactants to products, which will be used to monitor the reaction.
The wavelengths chosen for following the reactions were 235 nm
for N-chlorobenzylamine, 265nm for N-chlorodimethylamine,
255 nm for N-chloroglycine and 252 nm for N-chloro-2,2,2-
trifluoroethylamine.
Scheme 1. General equations of the reaction of tert-butyl hypochlorite
(tBuOCl) with nitrogenous compounds studied
The formation of the N-chloro compounds and their character-
ization is amply documented in the literature.[8,9,11,26,40]
Scheme 2. General equation to obtain tert-butyl hypochlorite (tBuOCl)
Rate equation
Taking into account the existing information for other chlorina-
tion processes involving organic nitrogenous compounds, it is
expected that the reaction between BuOCl and these com-
mixed asymmetric system (1:25), with the purpose of minimizing
the solvent effect. The thermostat used, Selecta Frigiterm S-382
(Selecta Frigiterm S-382, Barcelona, Spain), was used to ensure
consistency in temperature of 0.1°C. Absorbance-time data were
recorded by a computer equipped with data analysis software.
The volume of the tBuOCl solution added has always been less
4% with respect to the total volume of the reaction mixture, so
the acetonitrile used as solvent had no influence in the N-
chlorination process.
t
pounds can be described by the following rate equation:
t
d½ BuOClꢁ d½R1R2NClꢁ
b
c
a
t
v ¼ ꢀ
¼
¼ k½R1R2NHꢁ ½ BuOClꢁ ½Hþꢁ
dt
dt
(1)
pH measurements were made with a pH meter (PHM 82 Stan-
dard, Radiometer Copenhagen, Denmark), equipped with a com-
bined electrode (GK2401C) thermostated at 25 °C. The pH meter
was calibrated using standard solutions (supplied by Crison,
Barcelona, Spain) of pH 4.01, 7.02 and 9.26.
A set of experiments were carried out to determine the orders of
reaction (a, b and c) and the rate constant (k). In each experiment,
the reaction took place in excess of nitrogenous compound, with a
[R1R2NH]/[tBuOCl] mole ratio higher than 10, so that the nitroge-
nous compound concentration can be considered practically con-
All the kinetics experiments were carried out at 25.0 0.1 °C. In
all experiments, the ionic strength was adjusted to 0.5 M.
stant during the reaction and it can be included in kobs
.
Furthermore, the kinetic studies were carried out with a suffi-
cient amount of buffer solution in the reaction medium to main-
tain constant the pH of the medium while the temperature and
ionic strength were also maintained constant.
RESULTS
According to the previous discussion, the rate equation can be
expressed as follows:
Preliminary studies: selection of the wavelength
When the tBuOCl solution in acetonitrile is mixed with the aque-
ous solution of nitrogenous compound, the formation process of
the N-chloramine occurs quickly, followed by a slower decompo-
sition process (Scheme 3).
b
t
v ¼ kobs½ BuOClꢁ
(2)
The reaction rates of these two processes are very different,
and therefore their kinetics can be studied independently. The
half-time for the formation step, in the range of pH = 5–7, is less
than 1 s (t1/2 < 1 s). N-chloro amino acids decompose in aqueous
solution. The decomposition takes place relatively slow in neutral
medium or slightly acidic or basic but occurs much faster in
strong acid or basic media; in the range of pH 6.43–8.73. The rate
Order with respect to tert-butyl hypochlorite concentration
To verify the order of the reaction with respect to tBuOCl concen-
tration, the data were fitted to the first-order integrated equa-
tion. The software, which is included in the data control
programs of the stopped-flow spectrophotometer, fits
absorbance-time data to the first-order integrated equation writ-
ten exponentially (Eqn (3)).
obst
At ¼ A∞ þ ðAo ꢀ A∞Þꢂeꢀk
(3)
where A0 and At are the absorbance reading at zero and t times,
respectively, and A∞ is the absorbance when the reaction is com-
plete. kobs is the pseudo-first-order rate constant.
Scheme 3. General equations of the reaction of tert-butyl hypochlorite
(tBuOCl) with nitrogenous compounds
J. Phys. Org. Chem. 2014, 27 952–959
Copyright © 2014 John Wiley & Sons, Ltd.
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C. PASTORIZA
The good fit of the data to this equation allows us to confirm
that the reaction order with respect to the tBuOCl concentration
is one (b = 1) and to determine the kobs
.
All the experiments were repeated between four and seven
times. The values of the pseudo first-order rate constants, in-
cluded in the tables, represent the average value of all experi-
mentally obtained values. The deviations obtained in each case
are less than 5%. When larger deviations were obtained, the data
were discarded and the experiment was repeated.
Chlorination benzylamine, glycine and dimethylamine with
tBuOCl
Three sets of experiments were carried out with each amine at pH:
6.0, 6.5 and 7.0, approximately. In each series, all other parameters
were maintained constants (temperature, ionic strength, BuOCl
Figure 2. Influence of glycine concentration and pH on the rate con-
stant. T = 25 °C, I = 0.5 M, [tBuOCl] = 2.0 × 10ꢀ4 M, [H2PO4–/HPO42–]T = 0.1 M,
● pH = 6.02, ■ pH = 6.58, ▲ pH = 6.89
t
concentration and buffer solution concentration) except the amine
concentration that was varying of one experiment to other.
The experimental results obtained in the different sets of ex-
periments carried out with benzylamine, glycine and
dimethylamine show an increase in the rate constant (kobs) with
the increasing amine concentration for each pH value. The rate
constant also increases with increasing pH of the medium.
Figures 1–3 show the linear dependence between kobs and
[R1R2NH]T, which indicates that the reaction is first-order with re-
spect to the amine concentration.
Figure 4 shows the influence of pH on the second-order rate
constant (k2nd = kobs/[R1R2NH]T). All experimental values are in-
cluded in this figure. In each case, the value of the slope of the least
square fit is close to unit, which indicates that the exponent to
which proton is raised is c = ꢀ1. The influence of the buffer solu-
tion concentration on reaction rate for benzylamine and
dimethylamine was also studied. In these experiments, the con-
t
centrations of amine and BuOCl, as well as the temperature and
ionic strength of the medium were maintained constant, and only
the concentration of buffer solution was modified. Under these
conditions, the rate constant does not change appreciably on vary-
ing the total concentration of phosphate buffer solution.
Figure 3. Influence of dimethylamine concentration and pH on the rate
constant. T = 25 °C, I = 0.5 M, [tBuOCl] = 5.0 × 10ꢀ4 M, [H2PO4–/HPO24–
T = 0.1 M. ● pH = 6.04, ■ pH = 6.62, ▲ pH = 6.98
]
t
Chlorination of 2,2,2-trifluoroethylamine with BuOCl
The kinetic study of the reaction between 2,2,2-trifluoroethylamine
and tBuOCl was carried out by designing the five series of experi-
Figure 4. Influence of pH on k2nd. ● Benzylamine, □ Glycine,
▲ Dimethylamine
ments. Each of them was carried out at a different pH, between
5.24 and 6.82. In this pH range, the own amine solution can be
used as buffer solution. Thus, different buffer solutions of amine
containing 26, 37, 63, 82 and 93% of the free amine were prepared.
Figure 1. Influence of benzylamine concentration and pH on the rate
constant. T = 25 °C, I = 0.5 M, [tBuOCl] = 1.0 × 10ꢀ4 M, [H2PO4ꢀ/HPO24ꢀ
T = 0.1 M. ● pH = 6.11,■ pH = 6.67, ▲ pH = 7.06
]
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J. Phys. Org. Chem. 2014, 27 952–959

REACTIONS OF CHLORINATION
In all experiments, the rate constant increased with increasing
total amine concentration. However, the plot of kobs against
[R1R2NH]T shows a different kinetic behavior than the other three
amines studied (Fig. 5).
The results indicate that there is no first-order dependency with
respect to the amine concentration, a ≠ 1. Therefore, to determine
the dependency between the rate constant and the amine con-
centration, kobs must be expressed in logarithmic form (Eqn (4))
Table 1. Least square fits of the logarithmic equation for kobs
fR R NH
pH
Intercept
Slope
r
1
2
0.26
0.37
0.63
0.82
0.93
5.24
5.47
5.93
6.35
6.82
3.91 0.02
3.92 0.03
3.95 0.02
3.58 0.05
3.10 0.05
1.91 0.01
1.86 0.02
1.85 0.01
1.65 0.05
1.39 0.03
0.9999
0.9998
0.9999
0.9994
0.9992
À
Á
c
log kobs ¼ log k ½Hþꢁ
þ a log½R1R2NHꢁ
(4)
MECHANISM AND DISCUSSION
Figure 6 shows the linear relationships between log kobs and
log [R1R2NH]T for each series of experiments. Table 1 lists the
values of the slopes and intercepts obtained by least squares,
respectively.
According to Eqn (4), the slope value corresponds to the reac-
tion order with respect to amine concentration. This value is
greater than 1 (a> 1) and is observed to increase with decreasing
pH of the medium (Table 1). Therefore, a different reaction mech-
anism is necessary to propose for the chlorination reaction of
2,2,2-trifluoroethylamine by tBuOCl in order to explain the anoma-
lous dependence of the rate constant on the amine concentration.
In order to propose a possible reaction mechanism, it is neces-
sary to know which species are present in the reaction medium
when the BuOCl is mixed with the amine solution.
t
Alkyl hypochlorites are known to undergo hydrolysis in aque-
ous medium. The kinetics of formation and hydrolysis processes
t
of BuOCl was studied by M. Anbar and col.,[22] who proposed a
mechanism of acid–base catalysis.
t
However, considering that the BuOCl solution was prepared
in acetonitrile and as an asymmetric mixed (1:25) was used, the
tBuOCl is the only specie present when the reaction mixture oc-
curs. Moreover, under these experimental conditions, the rate
constants of the reactions studied are less than those of the chlo-
t
rination reactions with hypochlorite[26–28] so that the BuOCl is
going to be the chlorinating species.
On the other hand, the hydrolysis of tBuOCl cannot be the rate de-
termining step, because, in such case, the reaction rate would be in-
dependent of the concentration of the nitrogenous compound.
A possible mechanism through the protonated species has
also been proposed.[44] Although no values were obtained for
this equilibrium constant, it is expected that the pKa value will
be very small and close to zero (and may even be negative),
(Scheme 4).
Of the nitrogenous compounds studied, benzylamine, glycine
and 2,2,2-trifluoroethylamine have a primary amino group and
dimethylamine has a secondary amino group. All present ioniza-
tion equilibrium in aqueous solution can be represented, of gen-
eral form, by the following equation (Scheme 5).
From the pKa values for these nitrogenous compounds, we
can know what will be the distribution of species in the reaction
medium at different pH values at which the reactions were per-
formed. In the range of the pH studied, the protonated amine is
the predominant species in the chlorination of benzylamine
(pKa = 9.37[45]), glycine (pKa = 9.68[46]) and dimethylamine (pKa =
10.78[46]). However, in the range of pH in which the reaction of
2,2,2-trifluoroethylamine (pKa = 5.70[47]) was studied, both pro-
tonated and unprotonated amines may be present.
Figure 5. Influence of the 2,2,2-trifluoroethylamine concentration on
the rate constant. T = 25 °C, I = 0.5 M, [tBuOCl] = 1.0 × 10ꢀ3 M, ■ pH = 5.24,
□ pH = 5.47, ▲ pH = 5.93, ○ pH = 6.35, ● pH = 6.82
Scheme 4. Protonation equilibrium of tert-butyl hypochlorite (tBuOCl)
Figure 6. Experimental data fitting to kobs logarithmic equation. T = 25 °C,
I = 0.5M, [tBuOCl] = 1.0 × 10ꢀ3 M, ■ pH = 5.24, □ pH= 5.47, ▲ pH = 5.93,
○ pH= 6.35, ● pH = 6.82
Scheme 5. Ionization equilibrium of primary and secondary nitroge-
nous compounds in aqueous solution
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C. PASTORIZA
The values of the rate constants obtained in each series of
experiments for the benzylamine, glycine and dimethylamine
are (1.0 0.1) × 107 Mꢀ1 sꢀ1
,
(5.8 0.5) × 106 Mꢀ1 sꢀ1 and
(6.2 0.8) × 107 Mꢀ1 sꢀ1, respectively.
Formation of N-chloro-2,2,2-trifluoroethylamine
The kinetics of the chlorination of 2,2,2-trifluoroethylamine are
different from those of the other compounds. Therefore, a differ-
ent mechanism must be proposed for this reaction to explain the
variation in the reaction order with respect to the dependency of
the amine concentration on the pH medium.
The main difference between this amine and the other nitrog-
enous compounds studied is the pKa value, which is five units
lower than the pKa of the other nitrogenous compounds. This in-
dicates that this amine has acidic properties.
Scheme 6. Reaction mechanism proposed for the formation reaction of
N-chlorobenzylamine, N-chloroglycine and N-chlorodimethylamine with
tBuOCl
The reaction study was carried out in the pH range of 5.24–6.82.
Under these conditions, the free amine and its protonated form
coexist in the reaction medium. We therefore propose the
following reaction mechanism to explain the kinetic results
obtained (Scheme 7).
In accordance with the mechanism proposed, the overall rate
equation can be expressed as the sum of two terms in which the
possible steps through which the reaction may takes place are
included (Eqn (6))
Formation of N-chlorobenzylamine, N-chloroglycine and
N-chlorodimethylamine
Considering the available literature for the formation processes of
N-chloramines, a mechanism is proposed in which the two possi-
ble acid–base equilibriums of the reactive species are included.
Therefore, we can propose four determining steps of the rate
reaction that resulted from the combination of four species im-
plied in the equilibriums. Of these four possible steps, the reac-
t
tion between the BuOCl and the unprotonated amine is the
t
d½ BuOClꢁ d½R1R2NClꢁ
only step that justifies the experimental results. According to this
step, the rate constant increases with increasing pH value when
the reaction takes place at pH < pKa of the amino compound
(Scheme 6).
v ¼ ꢀ
¼
(6)
dt
dt
Â
Â
ÃÂ
t
¼ k1½R1R2NHꢁ BuOClꢁ þ k2½R1R2NHꢁ R1R2NHþ2 tBuOClꢁ
To obtain the rate equation deduced from the proposed
mechanism, it was taken into account that the acid–base equilib-
riums are faster than step 1, and a material balance was made to
each reagent present in the medium of reaction. Besides, it was
taken into account that all experiments were performed under
isolation conditions ([R1R2NH]T/[tBuOCl]T > 10, [R1R2NH]T ≈ con-
stant ) and in the presence of buffer solution ([H3O+] ≈ constant).
Moreover, the study of these reactions was carried out in a
range of pH = 6–7. In these pH conditions, the following will be
fulfilled: (a) [H+] > > > K2 and (b) K1 > > > [H3O+].
Given that the study was carried out under isolation condi-
tions, in which tBuOCl was the limiting reagent, and considering
the acid–base equilibrium of the amine, we can express the rate
constant kobs as follows (Eqn (7)):
Â
Ã
kobs ¼ k1½R1R2NHꢁ þ k2½R1R2NHꢁ R1R2NH2þ
(7)
Equation (7) shows the existence of a complex dependency
between the rate constant and the amine concentration.
Figure 7 shows the good linearity of the relationship between
kobs/[R1R2NH] and [R1R2NH+2]. This allows us to confirm the mechanism
proposed and thus to interpret and calculate the values of the
constants k1 and k2 by least squares fitting according to Eqn (7). The
Considering all the previous discussions, the rate equation de-
duced from the proposed mechanism, Eqn (5), allows us to calcu-
late the value of the kinetic constant for the determinant step (k1).
K2
½H3Oþꢁ
kobs ¼ k1ꢃ
ꢃ ½R1R2NHꢁT
(5)
following values were obtained: k1 = (220 22)
M ,
ꢀ1 sꢀ1
k2 = (4.83 0.08) × 104 Mꢀ2 sꢀ1
.
Formation of N-chloramines
The results of the kinetic study of the chlorina-
tion of four nitrogenous compounds to form
N-chloramines are described throughout this
study. The values of second-order rate constants
(Mꢀ1 sꢀ1) obtained from the reaction mecha-
nism proposed in each case are included in
Table 2.
This table also includes literature values of
the rate constants for the formation of these
N-chloramines with other chlorinating agents
(HOCl, NCS and NCNMPT) that were obtained
under similar experimental conditions to those
used in the present study. However, no
Scheme 7. Reaction mechanism proposed for the formation reaction of N-chloro-2,2,2-
trifluoroethylamine with tBuOCl
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J. Phys. Org. Chem. 2014, 27 952–959

REACTIONS OF CHLORINATION
In the case of N-chlorination reaction with HOCl, kinetic infor-
mation shows that the reaction rate decreases at values of pH >
pKa HOCl (pKa = 7.54). So, in strongly alkaline media, the N-
chlorination reactions with the other species (tBuOCl, NCS and
NCNMPT) have a higher reaction rate, because the active species
concentration is the highest while the HOCl concentration
decreases with increasing pH medium. Figure 8 shows the theo-
retical profiles deduced from reaction mechanism for the
benzylamine reaction with these chlorinating agents. In the case
t
of BuOCl and NCNMPT, the theoretical profiles have been ex-
trapolated to higher pH values than experimental results.
Figure 7. Plot kobs/[R1R2NH] versus [R1R2NH+2] for the chlorination of
t
2,2,2-trifluoroethylamine by BuOCl
previous kinetic studies of the reactions between nitrogenous
compounds and tBuOCl have been found so we cannot compare
the results obtained in this work with those obtained by the
other authors in similar conditions.
Comparison of the four chlorination agents included in Table 2
shows that the rate constants of formation of each N-chloramine
follow the order
kHOCl > k
> kNCS > kNCNMPT
tBuOCI
Besides, for each chlorinating agent, the rate constants
increase with increasing pKa of the amino group.
These reactions are rapid processes, with a strong depen-
dence on pH and that are favored by higher temperature.
Figure 8. Dependence of the rate constant with pH at 25 °C for
benzylamine reaction with different chlorinating agents: tBuOCl (this
work), NCS,[31] NCNMPT and[30] HOCl[26]
Table 2. Rate constants of the second-order (Mꢀ1 sꢀ1) reaction involving formation of N-chloramines
pKa
k/Mꢀ1 sꢀ1
HOCl
tBuOCl
NCS
NCNMPT
H – O– Cl
2,2,2-Trifluoroethylamine
5.7
-
220
6.8[31]
0.08[30]
Benzylamine
9.37
1.0 × 108[26]
1 × 107
4.3 × 105[31]
3.6 × 103[30]
Glycine
9.68
5.0 × 107[27]
0.58 × 107
6.8 × 107
6.3 × 105[11]
1.4 × 103[30]
11.3 × 107[48]
Dimethylamine
10.78
5.0 × 108[28]
9.8 × 107[49]
6.05 × 107[50]
1.5 × 107[10]
4.1 × 107[11]
10.0 × 104[30]
tBuOCl, tert-butyl hypochlorite; NCS, N-chlorosuccinimide; NCNMPT, N-chloro-N-methyl-p-toluensulfonamide.
J. Phys. Org. Chem. 2014, 27 952–959
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C. PASTORIZA
It is interesting to indicate that of these four chlorinating
agents, HOCl is the easiest to obtain, store and handle. The main
disadvantage in the use of the other three chlorinating agents is
the instability in aqueous solution, which makes their storage dif-
ficult. Once the aqueous solutions of these chlorinating agents
are prepared, their use should be immediate, because the hydro-
lysis reactions take place rapidly and in that case, the behavior
would be the same as the ClOꢀ.
In the case of compounds with a primary amino group, the
chlorination reaction may be complicated because of the possi-
ble formation of N,N-dichloramines.
The formation reaction of N,N-dichloramines could takes place by
an excess of chlorinating agent ([Chlorinating agent] > [R1R2NH]) or
by the disproportionation reaction of the monochloramines
formed. This reaction is important in acid media (pH < 3).
In all reactions studied here, the concentration of chlorinating
agent was maintained at least 10 times lower than the concen-
tration of the nitrogenous compound, and the pH was always
higher than 4. Thus, under the experimental conditions, the
fastest reaction that took place in the medium was the formation
of monochloramine, so that it was possible to study the kinetics
of the formation process without interference because of the
possible formation of dichloramines in the medium.
t
Figure 10. Taft relationship. ○ HOCl, □ NCS, ● BuOCl, ■ NCNMPT
Free-energy relationships
Reaction between the tBuOCl and a nitrogen compound is an ex-
ample of nucleophilic reaction on species which has an atom of
Cl+ and acting as electrophiles. These reactions of nucleophilic
substitution fulfill certain structure–reactivity relationships such
as: Brönsted equation, Taft equation and relations of Swain–
Scott or Ritchie among others. These relationships, in many
cases, help to clarify the way through which the reaction occurs
from the reactive state to the product state.
t
Figure 11. Swain–Scott relationship. ○ HOCl, □ NCS, ● BuOCl, ■ NCNMPT
In this paper, the free-energy relationships were established
for the four chlorinating agents: HOCl, NCS, tBuOCl and NCNMPT
with the nitrogenous compounds studied. Figures 9–12 show
the Brönsted relationship, Taft relationship and the nucleophile
relationships of Swain–Scott and of Ritchie for the results listed
in Table 2 along other available in the literature.
In these representations of free-energy, Figs. 9–12, we can ob-
serve that the point corresponding to the 2,2,2-trifluoroethylamine
in the reaction with tBuOCl does not follow the same trend as the
other amines with this chlorinating agent. This value of the rate con-
t
Figure 12. Ritchie relationship. ○ HOCl, □ NCS, ● BuOCl, ■ NCNMPT
stant reflects that the kinetic model proposed in order to justify the
kinetic results is different from the model proposed for the other ni-
trogenous compounds studied with this chlorinating agent. So, it
seems that this value of the second-order rate constant should not
be included to draw the trend lines of these structure–reactivity re-
lationships together with the values obtained for the three other ni-
trogenous compounds that have been studied.
t
Figure 9. Brönsted relationship. ○ HOCl, □ NCS, ● BuOCl, ■ NCNMPT
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J. Phys. Org. Chem. 2014, 27 952–959

REACTIONS OF CHLORINATION
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t
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> kNCS > kNCNMPT
tBuOCI
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t
dimethylamine), with BuOCl or with HOCl or ClOꢀ was found.
This behavior was expected because of the similarity between
the chlorinating agents: both have a Cl+ atom bonded to an ox-
ygen atom. Moreover, the k2nd values obtained in both reactions
are in the same order of magnitude, so that, any of these chlori-
nating agents may be used for the N-chloramines formation re-
actions being the only difference stability of the chlorinating
agent. In this sense, it is necessary to take precautions in the
preparation and storing of tBuOCl because hydrolysis could
place, and in that case, the reaction occurs directly between
the HOCl formed and the nitrogenous compound. For this rea-
t
son, the use of BuOCl, comparing with HOCl, is not an advan-
tage in aqueous solution, while in non aqueous solutions the
tBuOCl is the most suitable.
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SUPPORTING INFORMATION
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J. Phys. Org. Chem. 2014, 27 952–959
Copyright © 2014 John Wiley & Sons, Ltd.
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