Use of N-chloro-N-methyl-p-toluenesulfonamide in N-chlorination reactions

Article abstract of DOI:10.1002/poc.3127

Second-order rate constants (k₂) were determined for the addition of ten nitrogenous organic compounds (benzylamine, 2,2,2- trifluoethylamine chlorhidrate, methylamine chlorhidrate, glycine ethyl ester chlorhidrate, glycine, glycylglycine chlorhidrate, morpholine, pyperidine, pyperazine and dimethylamine) to the N-chloro-N-methyl-p-toluenesulfonamide (NCNMPT) in the formation reaction of N-chloramines in aqueous solution at 25 °C and ionic strength 0.5 M. The series of nucleophiles considered is structurally very varied and covers five pK_a units. The kinetic behaviour is similar for all compounds, being the elementary step the transfer of chlorine from the NCNMPT molecule to the nitrogen of the free amino group. These reactions were found first order in both reagents. The values of the rate constants indicate that the more basic amines produce N-chloramines more readily. Rate constants for the nucleophilic attack are shown to correlate with literature data for some of these nitrogenous organic compounds in their reaction with N-methyl-N-nitroso-p-toluenesulfonamide. Both reactions involve that the rate determining step is the attack of nitrogenous compounds upon electrophilic centre (Cl or else NO group). NCNMPT is a particularly interesting substrate, for which has not hitherto been published kinetic information, that allows us to assess the efficiency and the competitiveness of this reaction and compare it with other agents with a Cl⁺ atom. Copyright 2013 John Wiley & Sons, Ltd. N-chloro-N-methyl-p-toluensulfonamide is a particularly chlorinating agent. The kinetic behaviour has been studied in the formation reaction of N-chloramines using ten nitrogenous compounds. Copyright

Full text of DOI:10.1002/poc.3127

Research Article
Received: 26 December 2012,
Revised: 8 March 2013,
Accepted: 27 March 2013,
Published online in Wiley Online Library: 20 May 2013
(wileyonlinelibrary.com) DOI: 10.1002/poc.3127
Use of N-chloro-N-methyl-p-toluenesulfonamide
in N-chlorination reactions
Cristina Pastorizaa*, Juan Manuel Anteloa and Juan Crugeirasa
Second-order rate constants (k2) were determined for the addition of ten nitrogenous organic compounds
(benzylamine, 2,2,2-trifluoethylamine chlorhidrate, methylamine chlorhidrate, glycine ethyl ester chlorhidrate,
glycine, glycylglycine chlorhidrate, morpholine, pyperidine, pyperazine and dimethylamine) to the N-chloro-N-
methyl-p-toluenesulfonamide (NCNMPT) in the formation reaction of N-chloramines in aqueous solution at 25 ꢀC
and ionic strength 0.5 M. The series of nucleophiles considered is structurally very varied and covers five pKa units.
The kinetic behaviour is similar for all compounds, being the elementary step the transfer of chlorine from the
NCNMPT molecule to the nitrogen of the free amino group. These reactions were found first order in both reagents.
The values of the rate constants indicate that the more basic amines produce N-chloramines more readily.
Rate constants for the nucleophilic attack are shown to correlate with literature data for some of these nitrogenous
organic compounds in their reaction with N-methyl-N-nitroso-p-toluenesulfonamide. Both reactions involve that the
rate determining step is the attack of nitrogenous compounds upon electrophilic centre (Cl or else NO group).
NCNMPT is a particularly interesting substrate, for which has not hitherto been published kinetic information, that
allows us to assess the efficiency and the competitiveness of this reaction and compare it with other agents with a
Cl+ atom. Copyright © 2013 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper.
Keywords: N-chlorination; N-chloro-N-methyl-p-toluenesulfonamide; kinetics and mechanims; free relationships; N-chloramines
existing in the medium has been determined without
INTRODUCTION
distinguishing the kind of molecule in which the Cl+ is found.
These reactions take place with half-life in a wide range,
depending on the pH medium, but in any case always more than
a few minutes because if they were faster, then the iodometry
could not be used for monitoring the reaction.[11–17,7,18–20,8]
Nonetheless the information obtained from spectrophotomet-
ric studies allows us to establish that the overall reaction, repre-
sented by the stoichoimetric equations given above, should be
the superposition of the two independent processes taking
place in the reaction medium:
The most commonly used reagents for the preparation of N-
chloro compounds are among others: sodium hypochlorite,
N-chlorosuccinimide, Chloramine-T (CAT), Chloramine-B (CAB)
and tert-butylhypochlorite (tBuOCl).[1–8] All of them contain
a chlorine atom electrophile, positive chlorine, able to react
with the amino groups (R1R2NH) of amino acids, amines, amides
and other nitrogenous compounds, to form the corresponding
N-chloro compounds, in a reaction in that takes place the process
of breaking a NH bond and formation of the NCl bond.
CAT and CAB are two N-chlorosulfonamides often used as
analytical reagents and in kinetics studies.
•
•
a first rapid process to the formation of N-chloramine which
takes place with half-time less than a few seconds,
a second process where takes place the slow oxidative de-
composition of N-chloramine formed in the previous step,
with half-time more than a few minutes.
The review of the information obtained in the kinetic studies
of the reactions of a-amino acids with CAT[6] shows some contradic-
tions given that the reaction order with respect to the amino acid is
not the same in all cases, and even for the same amino acid, it
changes by changing the reaction medium and also provides con-
tradictory information, as the order with respect to these species is
very variable, taking positive, negative, whole or fractional values.
In most of these studies, the identification of the reaction prod-
ucts has also been carried out, and different stoichiometric equa-
tions for the processes studied have been suggested (Scheme 1).
In the case of the oxidation of amines with N-chlorosulfonamides,
the kinetic behaviour is similar to the amino acids although the
reaction products are usually aldehydes (Scheme 2).[9,10]
In these studies, several reaction mechanisms have been pro-
posed, in which an intermediate complex forms that in some
cases is the result of the nucleophilic attack of amine group over
N—Cl bond of oxidant agent. Most of the kinetic results come
from studies in which an iodometric method was used to carry
out the monitoring of the reaction, i.e. the Cl+ concentration
Scheme 3 is an example of this kind of reactions. This reaction
scheme corresponds with the kinetic study of the reaction
diethanolamine with CAT.[11]
This paper summarizes the results obtained in the kinetic
study of the chlorination reaction of ten nitrogenous organic
compounds which have a R1R2NH group, using N-chloro-N-
methyl-p-toluenesulfonamide (NCNMPT) as chlorinating agent.
* 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
J. Phys. Org. Chem. 2013, 26 551–559
Copyright © 2013 John Wiley & Sons, Ltd.

C. PASTORIZA, J. M. ANTELO AND J. CRUGEIRAS
Scheme 1. Examples of stoichiometric equations of CAT with amino acids
Scheme 2. Examples of stoichiometric equations of amines with N-chlorosulfonamides
Scheme 3. Proposed mechanism for the reaction diethanolamine with CAT
The NCNMPT is similar to N-chloramines CAT and CAB, the only
solvent to avoid its possible hydrolysis. The volume of the NCNMPT
solution added has always been less than 4% with respect to the total
volume of the reaction mixture; therefore, we believe that the acetoni-
trile, used as solvent, had no influence in the N-chlorination process.
difference is that is not possible to form the anionic specie. The
literature for this N-chlorosulfonamide is limited, but in any case
its reactivity should be similar to CAT or CAB.
For monitoring the reaction, a spectrophotometric method was
used, carrying out the reaction into a cell of stopped-flow spectro-
photometer which allowed us to study the process of formation of
N-chloramine separately of the decomposition process.
Kinetics
The UV–Visible spectrophotometers used for the previous studies were
Kontron Uvikon 930 and Varian Cary 1Bio equipped with thermostatized
cell-holder. The quartz spectrophotometer cells had the volume of
3.0 cm3. For the following of the faster reactions, the stopped-flow
spectrophotometer, Applied Photophysics DX.17MV, was used. A system
of mixed asymmetric (1:25) was used with the purpose of minimizing the
solvent effect
EXPERIMENTAL
Reagents
All reagents were obtained from commercial suppliers from Aldrich,
except NCNMPT which was synthesized. The nitrogenous compounds used,
R1R2NH, with a primary and secondary amino group were: benzylamine,
2,2,2-trifluoethylamine chlorhidrate, methylamine chlorhidrate, glycine
ethyl ester chlorhidrate, glycine, glycylglycine chlorhidrate, morpholine,
pyperidine, pyperazine and dimethylamine. These compounds were used
in aqueous solution; in some cases, an amount of acid or base was added
to reach in the reaction medium a pH value close to pH at which the kinetic
study will be done.
All the kinetics experiments were carried out at 25.0 ꢁ 0.1 ꢀC. The ionic
strength was adjusted to 0.5 M with NaClO4. The initial concentration of
NCNMPT (5 ꢂ 10ꢃ5–1 ꢂ 10ꢃ4 M) was always at least 10 times less than
the concentration of the other reagents presented.
A spectrophotometric method was used to monitor the reaction in
order to know the variation of absorbance with time. The reactions were
followed by measuring the variation of the absorbance at a fixed wave-
length, 245 nm for all compounds. The pseudo-first-order rate constants
(kobs) were obtained from adjustment of the data of absorbance-time to
equation At = A + (Ao-A ) ꢂ e-kobs t, being At the value of the absor-
All reactions were carried out under conditions such that the pH value
was maintained constant during the reaction; for this, we used different
buffer solutions trying that the total concentration of external buffer was
the same for all experiences performed with each amino compound. In
each case, from 2 to 5 series of experiences have been performed mod-
ifying the composition of buffer to obtain results at different pH values.
1
1
bance measured at time t, Ao the absorbance for the initial instant and
A
1
the absorbance corresponding to the end of the reaction. Under
the experimental conditions used, we have found that reactions follow
first-order kinetics with respect to the NCNMPT. A percentage of reaction
at least five half-lives was studied. The reactions were repeated between
8 and 10 times, showing in the present work the mean values and the
values of kobs were reproducible to within 3%.
The buffer solutions used were: CH3COOH/CH3COO–, H2PO4–/HPO42–
HEPES/HEPES– and H3BO3/H2BO–3.
,
A NaClO4 solution was also prepared and used to keep the ionic
strength constant at I = 0.5 M in the experiments.
A Radiometer pH GK2401C combined glass electrode was used to
measure pH. The pHmeter was calibrated with buffer solutions of
pH 4.01, 7.00 and 9.26 (Crison). The pH values were measured after the
kinetics measurements.
Synthesis of NCNMPT
This compound was obtained by the reaction of N-methyl-p-
toluenesulfonamide (98 %, Aldrich) with sodium hypochlorite in basic
medium. N-methyl-p-toluenesulfonamide was dissolved in sodium
hydroxide 0.5M until saturation and then a volume of sodium hypochlorite
(sodium hypochlorite moles as many as N-methyl-p-toluenesulfonamide
moles were dissolved) was added. The white precipitate obtained was
filtered vacuum, washed with very cold water and dried. Its purity was de-
termined by an iodometric method, and the results obtained were >99%.
The product thus obtained was stored in the refrigerator in topaz flask.
The solution used in the kinetic experiments was prepared every day,
from the NCNMPT synthesized in the laboratory, using acetonitrile as
RESULTS AND DISCUSSION
Previous studies. Selection of the wavelength
By mixing NCNMPT solution in acetonitrile with the aqueous
solution of nitrogenous compound, the process of formation of
the N-chloramine occurs quickly followed by a slower process
of decomposition (Scheme 4):
These two processes happen with very different reaction rates,
and therefore their kinetics can be studied independently. The
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Copyright © 2013 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2013, 26 551–559

USE OF NCNMPT IN N-CHLORINATION REACTIONS
nitrogenous compound concentration that was varying of one
experiment to other.
Figure 1 shows the experimental results obtained for the reac-
tion of the 2,2,2-trifluoroethylamine with NCNMPT. In this repre-
sentation, kobs against [Am]T, a linear increase in the rate
constant was observed with increasing the amine concentration
for each pH value, proving the first-order reaction in amine con-
centration. These experimental results also show the increase of
the rate constant with increasing pH for each amine concentration.
From linear regression analysis for each series of experi-
ments, kobs versus [Am]T, we obtain the rate constant of second-
order (k2nd = kobs/[R1R2NH]) for all nitrogenous compounds studied
(Table 1).
Scheme 4. General equation of the reaction of NCNMPT with nitroge-
nous compounds
half-time for the formation step in the range of pH = 4–10, is less
than 1 min (t1/2 < 1 min).
The N-chloroamino acids decompose in aqueous solution. This
decomposition is relatively slow in neutral, slightly acidic or basic
media, and is much faster in strong acid medium or basic medium.
In the range of pH 6.43–8.73, the rate constant for the decomposi-
tion of N-chloroglycine is kNCl = (4.3ꢁ 0.7)ꢂ10ꢃ6 sꢃ1, t1/2 = 44.7 h;
similar results were obtained for other N-chloroamino acids.[21,22]
The N-chloramines obtained from aliphatic amines are more
stable, increasing their decomposition rate in acid or strong basic
mediums.[23–26]
To select the suitable conditions for kinetic monitoring of the
reaction, previous spectrophotometric studies were performed
between 200 and 400 nm of all reactants and of the reaction mix-
ture. The superposition of these spectra justifies that upon
mixing of the reactants, there is a decrease of the absorption
band of the N-chlorosulfonamide and the appearance of a band
corresponding to the formation of N-chloramine. The spectro-
photometric results determine the wavelength at which there
is a significant variation in absorbance, from reactants to prod-
ucts, which will be used to monitor the reaction. In all cases,
the most suitable wavelength chosen for following the reaction
was 245 nm.
kobs ¼ k2nd ½R1R2NHꢄ
(3)
(4)
c
k2nd ¼ k½Hþꢄ
No literature was found about studies of the chlorination reac-
tions of nitrogenous compounds with NCNMPT. However, this
compound (NCNMPT) presents a similar structure to CAT, for
which there are studies about this type of reactions. This
suggests that the mechanism of reactions with NCNMPT or
CAT should be very similar.
The reaction mechanism proposed in the present study takes
into account the existing information about N-chlorination of
amino compounds, the chlorine species possibly present in solu-
tion and any equilibrium in which may be involved, so as the
possible reaction of hydrolysis of NCNMPT.
In general, we can postulate four possible steps of reaction
resulted of combination of two species of the amino compound
with two species of the chlorinating agent (Scheme 5).
For each one of these possibilities, we can obtain one rate ex-
pression. In these expressions, the concentration of different
species can be expressed in terms of the acidity, the total con-
centration of the amino compound, [Am]T and of the total con-
centration of the chlorinating agent, [NCNMPT]T.
Plotting log kobs against pH for each proposed step, we can
obtain theoretical profiles which allow us to deduce that only
one possibility, step 2, justifies the results obtained: the reaction
between the free NCNMPT and the unprotonated amino
compound, R1R2NH2. In all cases, the rate constant increases with
Rate equation
In order to determine the reaction order (a, b, c) and the rate con-
stant (k), a set of experiments were performed, in which the reac-
tion was carried out in excess of nitrogenous compound, with a
[R1R2NH]/[NCNMPT] mole ratio higher than 10. The nitrogenous
compound concentration can then be considered practically
constant during the reaction, and it can be included in the rate
constant (kobs). Moreover, the kinetic studies were carried out in-
cluding an amount of buffer solution in the medium of reaction,
enough to maintain constant the pH during the reaction, while
the temperature and ionic strength were maintained constant.
In accordance with above, the rate equation can be
expressed as:
d½NCNMPTꢄ d½R1R2NHꢄ
c
a
b
v ¼ ꢃ
¼
¼ k½R1R2NHꢄ ½NCNMPTꢄ ½Hþꢄ
dt
dt
(1)
b
v ¼ kobs½NCNMPTꢄ
(2)
Influence of the nitrogenous compound concentration
In order to study the influence of the nitrogenous compound
concentration on the rate constant were carried out a set of
experiences, between 4 and 6, at different pH values with each
nitrogenous compound. In each experiment, all parameters were
maintained constant (temperature, ionic strength, NCNMPT
concentration and buffer solution concentration) except the
Figure 1. Plot kobs versus [Am]T. [NCNMPT] = 10ꢃ4 M. ● pH = 4.99, ○
pH = 5.43, ■ pH = 5.67, □ pH = 6.04, ▲ pH = 6.40
J. Phys. Org. Chem. 2013, 26 551–559
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C. PASTORIZA, J. M. ANTELO AND J. CRUGEIRAS
Table 1. Second-order rate constants for N-chlorination to amino compounds from NCNMPT. T = 25 ꢀC, I = 0.5 M
Compound
pKa
[Buffer]T/M
pHm
k2nd/Mꢃ1 sꢃ1
2,2,2-Trifluoroethylamine
5.70[27]
4.04
4.99
5.53
5.67
6.04
6.40
6.19
6.59
7.06
7.87
8.17
7.78
8.23
8.53
8.91
9.08
9.60
9.16
9.38
9.68
5.91
6.51
7.03
8.06
8.60
8.68
8.85
8.98
9.65
6.11
6.61
7.17
7.28
5.97
6.55
7.16
0.1485 ꢁ 0.006
0.76 ꢁ 0.02
1.45 ꢁ 0.04
2.05 ꢁ 0.05
2.7 ꢁ 0.1
3.2 ꢁ 0.1
3.34 ꢁ 0.01
4.1 ꢁ 0.1
Glycine ethyl ester
Glycylglycine
Benzylamine
Glycine
7.75[28]
8.25[29]
9.37[30]
9.68[29]
10.72[31]
8.55[32]
[HEPES/HEPES–]T = 0.01 M
[H3BO3/H2BO–3]T = 0.01 M
[H3BO3/H2BO–3]T = 0.1 M
[H3BO3/H2BO–3]T = 0.2 M
[H2PO–4/HPO24–]T = 0.1 M
[H3BO3/H2BO–3]T = 0.2 M
1.91 ꢁ 0.07
6.1 ꢁ 0.2
9.4 ꢁ 0.3
4.2 ꢁ 0.1
7.2 ꢁ 0.1
10.3 ꢁ 0.4
(7.5 ꢁ 0.1) ꢂ 102
(11.5 ꢁ 0.1) ꢂ 102
(30 ꢁ 2) ꢂ 102
337 ꢁ 17
490 ꢁ 5
897 ꢁ 32
Methylamine
Morpholine
0.76 ꢁ 0.02
2.58 ꢁ 0.04
9.3 ꢁ 0.1
400 ꢁ 8
1505 ꢁ 30
2206 ꢁ 73
2226 ꢁ 55
(5.2 ꢁ 0.2) ꢂ 103
(17.9 ꢁ 0.6) ꢂ 103
2.598 ꢁ 0.001
7.2 ꢁ 0.1
Pyperazine
9.71[32]
[H3BO3/H2BO–3]T = 0.1 M
[H2PO–4/HPO24–]T = 0.1 M
Dymethylamine
10.78[29]
25.1 ꢁ 0.2
26.4 ꢁ 0.7
9.6 ꢁ 80.1
30.3 ꢁ 0.3
113 ꢁ 1
Pyperidine
11.12[29]
[H2PO–4/HPO24–]T = 0.1 M
Scheme 5. Possible steps for the reaction of NCNMPT with nitrogenous compounds
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USE OF NCNMPT IN N-CHLORINATION REACTIONS
increasing the pH value when the reaction takes place at pH< pKa
of the amino compound.
According to these considerations, the reaction mechanism
involves the following steps (Scheme 6).
Assuming that the acid–base equilibriums are faster than the
k2 step, the overall rate equation derived for the proposed mech-
anism (Scheme 6) is the following:
Whereas the second-order constant is defined as k2nd = kobs2/[Am]T,
it is possible to calculate the kinetic constant for the determinant
step (k2), through the following equation:
K2 þ ½H3Oþꢄ
k2 ¼ k2nd
ꢂ
(8)
K2
The rate equation deduced from the reaction mechanism
proposed, and other simplified equations derived from it which
have been established, can justify the following experimental
results: the order to reaction with respect to reagents concen-
tration (R1R2NH and NCNMPT) or the importance of ionization
equilibrium for the amino compound. Also, it allows calculating
the rate constant k2 for each experience and, the constancy of
values obtained will be an evidence that the mechanism of
the reaction is correct. Furthermore, the rate equation verifies
the influence of pH on the reaction rate for all the compounds
studied, and the rate constant increases with increasing the
pH value when the reaction takes place at pH < pKa of the
amino compound.
The average values of k2 obtained from the equations de-
rived from the reaction mechanism proposed are compiled in
Table 2.
The k2 values may be considered as the rate constant for the
formation reaction of N-chloramines for each nitrogenous com-
pound, and they can be used to calculate some k2nd theoretical
values to any pH value that allow us to draw the curve log k2nd
versus pH.
d ½R1R2NHꢄ
v2 ¼
¼ k2 ꢂ ½R1R2NHꢄ ꢂ ½NCNMPTꢄ
(5)
dt
Bearing in mind the mass balances and the acid–base equilib-
rium in the medium, this equation is equivalent to
K2
K1
v2 ¼ k2 ꢂ ½AmꢄT ꢂ
ꢂ ½NCNMPTꢄT ꢂ
K2 þ ½H3Oþꢄ
K1 þ ½H3Oþꢄ
(6)
The experiences were performed in isolated conditions, so the
concentration of amino compound was kept practically constant
([Am]T ꢅ constant), and in presence of buffer solutions in each
experience [H+] ꢅ constant.
These studies were performed at values of pH > 4. In these
conditions, K1>> > [H+], so that this suggests that almost all
the NCNMPT is present as unprotonated species and the above
equation reduces to v2 = kobs ꢂ [NCNMPT]T where
K2
kobs2 ¼ k2 ꢂ ½AmꢄT ꢂ
(7)
K2 þ ½H3Oþꢄ
K2
k2nd ¼ k2 ꢂ
(9)
K2 þ ½H3Oþꢄ
The values of the constants k2nd obtained from Eqn 9 along
with the theoretical profile are plotted in Figs. 2 and 3, for amino
compounds with a primary and secondary amino group, respec-
tively. The good fits in these figures support the proposed
reaction mechanism.
The results included in Table 2 show a significant increase in
the constant value k2 with increasing the pKa value of the amino
compound, verifying the Brönsted equation as can be seen in
Fig. 4. This fact indicates that the more basics amines produce
N-chloramines more readily.
Scheme 6. Reaction mechanism proposed for the N-chlorination reac-
tions with NCNMPT
Table 2. Second-order rate constants for N-chlorination of nitrogenous compounds by NCNMPT together with the corresponding
structural parameter (Σs*) and nucleophilicity constants (N+ and n)
k2/Mꢃ1 sꢃ1
Σs*[33,34]
n[38]
N+
[29,35]
R1R2NH
pKa
2,2,2-Trifluoroethylamine
Glycine ethyl ester
Glycylglycine
Benzylamine
Glycine
Methylamine
Morpholine
Pyperazine
5.70
7.75
8.25
9.37
9.68
10.72
8.55
9.73
10.78
11.12
0.08 ꢁ 0.01
1.90
1.69
1.58a
1.20
0.92
0.98
1.16
0.74a
0.49
0.35
4.08
4.59b
4.59
5.04
5.11]
5.21
5.16
5.46
5.83
5.67
3.45
13 ꢁ 2
4.40
4.69
6.20
6.51
6.56
7.14
7.44
7.95
7.92
17 ꢁ 2
(3.6 ꢁ 0.6) ꢂ 103
(1.4 ꢁ 0.2) ꢂ 103
(5 ꢁ 1) ꢂ 104
(2.4 ꢁ 0.7) ꢂ 103
(3.65 ꢁ 0.07) ꢂ 104
(10 ꢁ 1) ꢂ 104
(1.2 ꢁ 0.2) ꢂ 106
Dimethylamine
Pyperidine
acalculated from empirical equations of Hall for primary and secondary amines.
bcalculated by extrapolation of the linear correlation between N+ and n, considering N+ = 4.40.
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C. PASTORIZA, J. M. ANTELO AND J. CRUGEIRAS
Figure 4 shows that there is a small difference among the
behaviour of primary amines and of secondary amines. However,
in both cases, there is a good straight line of slope next to 1
between log k2 and pKa, s = (1.1 ꢁ 0.1) and s = (0.9 ꢁ 0.2) for pri-
mary and secondary amines, respectively. These results indicate
that the transition state is the nearest to products state. Further-
more, this good linear Brönsted relationship also indicates that
no change occurs in the reaction rate determining step.
If the rate constants are related to the amino compounds pKa,
it seems reasonable that the rate constants for the N-chlorination
of amines also ought to be related to some structural parameter.
Hall[28] reported that the pKa of amines depend linearly on
Taft’s parameter, Σs*, quantifying the polar character of the
substituents:
Primary amines : pKa ¼ 13:23 ꢃ 3:14 Σsꢆ
Secondary amines : pKa ¼ 12:13-3:23 Σsꢆ
(10)
(11)
Figure 2. Experimental values and theoretical curve deduced from
mechanism for primary amino compounds. ● 2,2,2-trifluoroethylamine
(pKa = 5.70), ■ glycine ethyl ester (pKa = 7.75), 5 glycylglycine (pKa =
8.25), ▲ benzylamine (pKa = 9.37), ○ glycine (pKa = 9.68), □ methylamine
(pKa = 10.72)
If we accept as valid the Hall equations, as they have been cal-
culated for a big number of compounds, we can use them to ob-
tain Taft’s parameter values for glycylglycine and for pyperazine
(Σs* = 1.58 and Σs* = 0.74, respectively).
Table 2 lists the values of k2 for the ten amino compounds
studied, together with the corresponding values of pKa and of
Σs*.
Moreover, taking into account the fairly good linear relation-
ships found for the log k2 against pKa and for the pKa against
Σs* also ought to be a good relationship between log k2 against
Σs* in compliance with Taft’ equation, Fig. 5. Linear regression
yields the following equation.
log k ¼ ð7:8 ꢁ 0:6Þ ꢃ ð4:2 ꢁ 0:5ÞΣsꢆ r ¼ ꢃ0:9381
r ¼ ꢃð4:2 ꢁ 0:5Þ
(12)
(13)
This good linear relationship found allows us to justify that for
all amino compounds studied, the same mechanism of the reac-
tion has been proposed.[36,1] The value obtained for r indicates
that is very sensitive to the polarity of substituents, and, in
Figure 3. Experimental values and theoretical curve deduced from
mechanism for secondary amino compounds. ○ morpholine (pKa = 8.55),
▲ pyperazine (pKa = 9.71), ● dimethylamine (pKa = 10.78), ■ pyperidine
(pKa = 11.12)
Figure 4. Brönsted relationship, log k2 versus pKa. ● primary amino
group, ○ amine secondary group. 1- 2,2,2-trifluoroethylamine, 2- glycine
ethyl ester, 3- glycylglycine, 4- benzylamine, 5- glycine, 6- methylamine,
7- morpholine, 8- pyperazine, 9- dimethylamine, 10- pyperidine
Figure 5. Taft representation, log k2 versus Σs*. ● primary amino group,
○ secondary amino group. 1- 2,2,2-trifluoroethylamine, 2- glycine ethyl
ester, 3- glycylglycine, 4- benzylamine, 5- glycine, 6- methylamine, 7-
morpholine, 8- pyperazine, 9- dimethylamine, 10- pyperidine
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J. Phys. Org. Chem. 2013, 26 551–559

USE OF NCNMPT IN N-CHLORINATION REACTIONS
general, it can be said that increasing the polarity of the substit-
uents groups decreases the nucleophilicity of the amino
compound and consequently decreases the rate constant.
Ritchie’s and Swain–Scott’s correlations were analyzed to
understand the reactivity of the different nucleophiles in their
reaction with NCNMPT. The comparison of the empirical param-
eters N+ and n (Table 2) shows that there is a good linear corre-
lation with a slope of 2.8 ꢁ 0.2; this indicates that the rate
constants for the nucleophilic addition reactions to electrophiles
(which is defined for the parameter N+) are significantly higher
than the corresponding rate constants for the nucleophilic sub-
stitution reactions with methyl halides (which is defined for the
parameter n).[37,38]
Figures 6 and 7 show the representations for the equations of
Swain–Scott and Ritchie; in both cases, we can see a good linear-
ity among all compounds studied.
In the representation of Swain–Scott, Fig. 6, despite the good
linearity observed, the slope obtained in the least squares fit of
log k2 against n is s = 3.8 ꢁ 0.3. This value is greater than the
values estimated by Swain–Scott for nucleophilic reactions with
amines (s = 0.6–1.2)[39]; however, the good linear correlation
obtained suggests that it is because the n values considered
for each amino compounds studied are defined for reactions in
which the nucleophilic attack occurs on a carbon atom and not
on a chlorine atom.
On the other hand, this fact allows us to consider the value of s
as an additional criterion for the participation of the nucleophile
in the transition state. The difference in the value of the slope for
the substitution reaction of the chlorine atom, s = 3.8 ꢁ 0.3,
compared with the values that would be expected, s = 0.6–1.2,
indicates that the bond between the chlorine and the nucleo-
phile in the transition state is formed more easily than the bond
with the carbon for which are defined the n parameters.[40]
This result is similar to that found in other nucleophilic reac-
tions on chlorine atom. Gerritsen and Margerum[41] have studied
the reaction of HOCl with different nucleophilic anions, finding a
good correlation of Swain–Scott with a slope value of 4.7 ꢁ 0.1.
Figure 7 shows a good fit to the Ritchie equation, where N+ is
a parameter characteristic of nucleophile reactivity. The slope
of this correlation is 1.3 ꢁ 0.1, which is close to the theoretical
value of unity, shows that the electrophile–nucleophile reac-
tions fulfill Ritchie’s equation, including the reactions that
occur through a concerted mechanism of nucleophiles with
a chlorine atom.
This means that all reactions studied are of type SN2 reactions,
which take place by a concerted mechanism, and small devia-
tions observed in the linearity are due to that the nucleophile
character of the amino compounds studied are susceptible to
sterics effect.[29]
On the other hand, the rate constants obtained in the present
work for some of the amino compounds studied in their reaction
with NCNMPT were compared with the values of the rate
constant found in the literature for these amino compounds in
their reaction with N-methyl-N-nitroso-p-toluenesulfonamide
(MNTS).[42,43] The difference between both reagents is that the
NCNMPT has a NCl bond and the MNTS has a NNO bond.
As can be seen in Fig. 8, the rate constants referring to the
chlorination process are greater than those referred to
nitrozation processes, indicating that the transfer of Cl+ to amino
compounds takes place in a faster process than the transfer of
NO group of the same compound under the same conditions.
Figure 6. Swain–Scott representation, log k2 versus n. ● primary amino
group, ○ secondary amino group. 1- 2,2,2-trifluoroethylamine, 2- glycine
ethyl ester, 3- glycylglycine, 4- benzylamine, 5- glycine, 6- methylamine,
7- morpholine, 8- pyperazine, 9- dimethylamine, 10- pyperidine
Figure 7. Ritchie representation, log k2 versus N+. ● primary amino
group, ○ secondary amino group. 1- 2,2,2-trifluoroethylamine, 2- glycine
ethyl ester, 3- glycylglycine, 4- benzylamine, 5- glycine, 6- methylamine,
7- morpholine, 8- pyperazine, 9- dimethylamine, 10- pyperidine
Figure 8. Plot log kNCNMPT versus log kMNTS. 3- glycylglycine, 5- glycine,
6- methylamine, 7- morpholine, 8- pyperazine, 9- dimethylamine, 10-
pyperidine
J. Phys. Org. Chem. 2013, 26 551–559
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C. PASTORIZA, J. M. ANTELO AND J. CRUGEIRAS
Figure 9. Brönsted equation. ● NCNMPT, ○ MNTS. 3- glycilglycine, 5- glycine, 6- methylamine, 7- morpholine, 8- pyperazine, 9- dimethylamine,
10- pyperidine
In both reactions, a nucleophilic attack of the amino com-
pound take place on the chlorine atom of NCNMPT or failing
on NO group of MNTS.
In any case, the good linearity obtained indicates that the N-
chloramines or N-nitrosamines are formed more easily from the
more basic amines.
Figure 9 compares the Brönsted equation for the reactions
using NCNMPT or MNTS as electrophiles, log k versus pKa.
Due to the similarity found between both reactions, a good
agreement in the nucleophilic correlations of Swain–Scott
(Fig. 10) and of Ritchie (Fig. 11) may be expected.
The previous nucleophilic representations show the agree-
ment among the experimental results obtained for the reaction
with NCNMPT, compared with bibliographic results for the reac-
tion with MNTS that were obtained with different amino com-
pounds also studied in the present work. This again allows us
to corroborate the proposed mechanism and suggests that the
transition state of the reaction studied in this work resembles
to the reaction with MNTS: a transition state corresponding to
a concerted mechanism closer to the state of the products.
CONCLUSIONS
NCNMPT is an effective chlorination agent by direct transfer of
its Cl+ atom to N atom amine. The kinetic study of reaction of
the NCNMPT with ten amino compounds shows that the reac-
tion is of first-order respect to each of the reagents. We proposed
a reaction mechanism in which in the determining step is pro-
duced the nucleophilic attack of the amino no protonated com-
pound over the chlorine atom of the unprotonated species of
the NCNMPT when pH < pKa of the amino compound in all com-
pounds studied.
Figure 10. Swain–Scott representation. ● NCNMPT, ○ MNTS. 3- glycylglycine,
5- glycine, 6- methylamine, 7- morpholine, 8- pyperazine, 9- dimethylamine,
10- pyperidine
Moreover, the kinetic behaviour of this substrate is similar to
MNTS; in both cases, the reaction takes place by concerted mech-
anism. This type of nucleophilic substitution reactions fulfill certain
structure–reactivity relationships such as: Brönsted equation, Taft
equation and the relationships of Swain–Scott and Ritchie.
SUPPORTING INFORMATION
Supporting information includes: Figures of kobs versus [Am]T for
all amino compounds studied, examples of the theoretical pro-
files of log kobs versus pH and Hall’s representation.
REFERENCES
[1] M. Deborde, U. von Gunten, Water Res. 2008, 42, 13.
[2] J. M. Antelo, F. Arce, J. Crugeiras, M. Parajó, J. Phys. Org. Chem. 1997,
10, 631.
Figure 11. Ritchie representation. ● NCNMPT, ○ MNTS. 3- glycylglycine,
5- glycine, 6- methylamine, 7- morpholine, 8- pyperazine, 9- dimethylamine,
10- pyperidine
[3] T. Higuchi, A. Hussain, I. H. Pitman, J. Chem. Soc. B 1969, 626.
wileyonlinelibrary.com/journal/poc
Copyright © 2013 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2013, 26 551–559

USE OF NCNMPT IN N-CHLORINATION REACTIONS
[4] J. M. Antelo, F. Arce, J. Franco, M. C. Garcia Lopez, M. Sanchez, A.
Varela, Int. J. Chem. Kinet. 1988, 20, 397.
[5] M. M. Campbell, G. Johnson, Chem. Rev. 1978, 78, 65.
[6] B. T. Gowda, D. S. Mahadevappa, J. Chem. Soc. Perkin Trans. 2 1983, 323.
[7] B. T. Gowda, M. Shetty, J. Phys. Org. Chem. 2004, 17, 848.
[8] M. K. Veeraiah, A. S. Ananda Murhty, N. M. Made Gowda, Synth. Re-
act. Inorg. Met. Org. Nano-Met. Chem. 2010, 40, 225.
[26] J. M. Antelo, F. Arce, J. Casado, E. Novoa, M. E. Sánchez, A. Varela,
Anal. Quim. 1987, 83, 589.
[27] W. P. Jencks, J. Regenstein, Handbook of Biochemistry, 2nd ed.
(Ed: H. A. Soper) Chemical Rubber Co., Cleveland, OH, 1970.
[28] H. K. Hall, Jr., J. Am. Chem. Soc. 1957, 79, 5441.
[29] C. K. M. Heo, J. W. Bunting, J. Chem. Soc. Perkin Trans. 2
1994, 2279.
[9] S. Ananda, T. Demappa, D. S. Mahadezappa, N. M. Made Gowda, Int.
J. Chem. Kinet. 1996, 28, 873.
[10] Puttaswamy, T. M. Anuradha, R. Ramachandrappa, N. M. Gowda, Int.
J. Chem. Kinet. 2000, 32, 221.
[30] W. H. Carothers, C. F. Bickford, G. J. Hurwitz, J. Am. Chem. Soc. 1927,
49(11), 2908.
[31] A. E. Martell, R. M. Smith, Critical Stability Constants, Vol. 1, Plenum
Press, New York, 1974.
[11] J. M. Antelo, F. Arce, J. Casado, A. Varela, Anal. Quím. 1982, 78(1), 63.
[12] B. T. Gowda, R. V. Rao, J. Indian Chem. Soc. 1987, 64(8), 467.
[13] B. T. Gowda, R. V. Rao, Indian J. Chem. A, 1988, 27A(1), 39.
[14] B. T. Gowda, R. V. Rao, J. Indian Chem. Soc. 1987, 64(7), 403.
[15] K. S. Rangappa, K. Manjunathaswamy, M. P. Raghavendra, N. M.
Made Gowda, Int. J. Chem. Kinet. 2002, 34, 49.
[16] N. Grover, N. Kambo, S. K. Upadhyay, Int. J. Chem. Kinet. 2002, 34, 603.
[17] B. Th. Gowda, B. H. A. Kumar, Oxid. Commun. 2003, 26(3), 403.
[18] K. N. Shivananda, R. V. Jagadeesh, Puttaswamy, K. N. Mahendra, J.
Mol. Catal. A: Chem. 2006, 255, 159.
[19] K. N. Shivananda, B. Lakshmi, R. V. Jagadeesh, Puttaswamy, K. N.
Mahendra, Appl. Catal. Gen. 2007, 326, 202.
[20] Puttaswamy, V. Nirmala, R. V. Jagadeesh, Chin. J. Chem. 2008, 26(3), 537.
[21] X. L. Armesto, M. Canle, M. Losada, J. A. Santaballa, Int. J. Chem.
Kinet., 1993, 25, 1.
[32] A. E. Martell, R. M. Smith, Critical Stability Constants, Vol. 2, Plenum
Press, New York, 1975.
[33] A. Willians, Free Energy Relationships in Organic and Bio-organic
Chemistry, (Ed. The Royal Society of Chemistry), 2003.
[34] D. D. Perrin, B. Dempsey, E. P. Serjeant, pKa Prediction for Organic
Acids and Bases, Chapman & Hall, London, 1981.
[35] C. D. Ritchie, Can. J. Chem. Soc. 1986, 64, 2239.
[36] L. Abia, X. L. Armesto, M. Canle, M. V. García, M. Losada, J. Santaballa,
Tetrahedron 1998, 54, 521.
[37] J. P. Richard, M. M. Toteva, J. Crugeiras, J. Am. Chem. Soc. 2000, 122,
1664.
[38] J. W. Bunting, J. M. Mason, C. K. M. Heo, J. Chem. Soc. Perkin Trans. 2,
1994, 2291.
[39] J. Koskikallio, Acta Chem. Scand., 1969, 23, 1490.
[40] J. M. Antelo, J. Crugeiras, J. R. Leis, A. Rios, J. Chem. Soc. Perkin Trans.
2 2000, 2071.
[41] C. M. Gerritsen, D. W. Margerum, Inorg. Chem., 1989, 29(15),
2757.
[22] X. L. Armesto, M. Canle, M. Losada, J. A. Santaballa, J. Chem. Soc.
Perkin Trans. 2 1993, 181.
[23] J. M. Antelo, F. Arce, M. C. Castro, J. Crugeiras, J. C. Pérez-Moure, P.
Rodríguez, Int. J. Chem. kinet. 1995, 27, 703.
[42] L. García-Río, E. Iglesias, J. R. Leis, E. Peña, A. Rios, J. Chem. Soc. Perkin
[24] J. M. Antelo, F. Arce, M. Parajó, J. Phys. Org. Chem. 1996, 9, 447.
[25] J. M. Antelo, F. Arce, D. Casal, P. Rodríguez, A. Varela, Tetrahedron
1989, 45, 3955.
Trans. 2, 1993, 29.
[43] A. Castro, J. R. Leis, M. E. Peña, J. Chem. Soc. Perkin Trans. 2, 1989,
1861.
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