Arenesulfonylation of N-alkylanilines: reaction kinetics and mechanism

Article abstract of DOI:10.1007/s11172-017-1846-0

Kinetic regularities of arenesulfonylation of N-alkylanilines in binary water-organic solvents of variable composition have been studied. The rate constants for these reactions increase with increasing the water content in a system. The steric factor has

Full text of DOI:10.1007/s11172-017-1846-0

Russian Chemical Bulletin, International Edition, Vol. 66, No. 6, pp. 999—1006, June, 2017
999
Arenesulfonylation of N-alkylanilines: reaction kinetics and mechanism
L. B. Kochetova, T. P. Kustova, L. V. Kuritsyn, and A. A. Katushkin
Ivanovo State University,
39 ul. Ermaka, 153025 Ivanovo, Russian Federation.
Tel.: +7 (4932) 37 37 03. E-mail: kustova_t@mail.ru
Kinetic regularities of arenesulfonylation of N-alkylanilines in binary water-organic solvents
of variable composition have been studied. The rate constants for these reactions increase with
increasing the water content in a system. The steric factor has the decisive influence on reactiv-
ity of N-alkylamines. The character of the influence of the composition and nature of
a solvent on the rate constants for arenesulfonylation was discussed with the assistance of results
of quantum chemical simulation of molecular complexes of the nucleophiles studied with the
components of the binary systems. Calculation of potential energy surface for the reaction of
N-methylaniline with benzenesulfonyl chloride showed that in the gas phase the process occurs
by the SN2 mechanism.
Key words: sulfonylation, N-alkylanilines, arenesulfonyl chlorides, aqueous organic solvents,
quantum chemical simulation, reactions mechanisms.
Elucidation of the correlation between kinetic charac-
teristics of reactions and molecular parameters of the re-
actants allows one to predict the reactivity of compounds
in various processes, to quantificate it, and also presents
a tool for the indirect establishment of the reaction
mechanisms enabling the targeted management of the
reaction course.
suggesting the basicity of the amino groups of amino acids
and dipeptides to be a key factor in their nucleophilic
reactivity.3 It should be noted that the data on quantitative
studies of acetylation and benzoylation of amines in various
media is covered in literature much more widely compared
to the quantitative characteristics of sulfonylation of these
compounds.
Nowadays, kinetics and mechanisms of the acyl trans-
fer are intensively studied.1—7 We have shown,1—4 that
reactivity of substituted arylamines, aminobenzoic acids
and diamino acids in N-acylation was determined by both
electronic and orbital characteristics of nucleophilic agents.
Quantum chemical modeling of the reaction path for
D,L--alanine and 3-nitrobenzenesulfonyl chloride (1)
under conditions whereby mono-, di-, and trihydrates of
alanine are formed has shown that the reaction energy
profile depends significantly on the specific solvation of
alanine by water molecules.1 Rate constants and activation
parameters for reactions of morpholine and piperidine
with 4-toluenesulfonyl chloride and benzenesulfonyl
chloride in water (40 wt.%)—1,4-dioxane mixture were
determined.2 Using the method for construction of the
potential energy surface (PES), the reaction between pi-
peridine and benzenesulfonyl chloride was established to
proceed according to the SN2-mechanism. Under the same
conditions, kinetics of arenesulfonylation of - and
-alanine, dipeptides derived therefrom, glycylglycine,
L-proline, and L-asparagine was studied. Correlations
between the rate constants for arenesulfonylation of
amino acids and dipeptides, and the rate constants for
interaction of the latter compounds with acyl donors
(benzoyl chlorides and picryl benzoate) were established,
Studies of the processes of sulfamide formation is of
current concern, since the products of such reactions have
valuable properties (such as e.g., thermostability and
hydrolytic stability in alkaline media8) making these com-
pounds useful in synthesis of thermostable and chemi-
cally stable polymers. Being bioactive, these compounds
are widely used in pharmacology and medicine as
anaesthetics, in treatment of bacterial infections, dis-
play diuretic and antihypertensive action, inhibit en-
zymes,9—12 etc.
N-Alkylated anilines extend the capabilities of or-
ganic and pharmaceutical synthesis due to a presence of
aromatic ring and alkyl group in their molecules, allowing
functionalization of each of these moieties. Literature data
on reactivity of mixed amines in reactions affording
compounds containing the sulfamide bond are rather
scarce.13,14 In the present study, kinetic data for the reac-
tions of N-methyl, N-ethyl, and N-butylanilines (2a—c)
with compound 1 in mixtures of water with EtOH, propan-
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 0999—1006, June, 2017.
1066-5285/17/6606-0999 © 2017 Springer Science+Business Media, Inc.

1000
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 6, June, 2017
Kochetova et al.
Measurement errors for kac and kh were calculated with a confi-
dence level of 0.95.
2-ol, 1,4-dioxane, THF and acetonitrile of variable com-
position were analyzed within the framework of the
QSPR-approach (Quantitative Structure — Property
Relationship).
Secondary amines 2a—c (Aldrich, 98—99%) were used as
purchased. Compound 1 («pure grade») was recrystallized from
a (9 : 1) hexane—propan-2-ol mixture with addition of activated
carbon; 1,4-dioxane («pure grade») and THF («pure grade») were
stored over KOH for seven days, and distilled over sodium
metal. Ethanol («pure grade»), propan-2-ol («pure grade»), and
acetonitrile («pure grade») were dried and distilled with Vigreux
column at atmospheric pressure. Water—organic solvents were
prepared using bidistillate obtained on a DW-1 demineralized
water generator.
R = Me (a), Et (b), Bu (c)
Experimental
Results and Discussion
N-Alkylanilines 2a—c react with compound 1 according to
Results of the previous kinetic study of reactions be-
tween a series of secondary alkylamines and arenesulfonyl
chlorides in individual organic solvents15 suggest that on
a number of parameters these processes are similar to
arenesulfonylation of anilines. At the same time, sub-
stituents at the amino group of the unsymmetric amines
have a noticeable effect on their reactivity. For example,
rate constants for the reaction of substituted N-iso-
butylanilines (ArNHBui) and sulfonyl chloride 1 are signifi-
cantly lower (Table 1) compared to the corresponding less
basic anilines ArNH2 (cf pKa = 5.43 for the protonated
PhNHBui and 4.60 for PhNH2).16 On the one hand, intro-
duction of an alkyl substitutent into the amino group of
an arylamine increases the nucleophilicity of the N atom,
rising its reactivity. On the other hand, the alkyl radical
creates steric hindrances during formation of an activated
complex, what should diminish the acylation rate. As can be
seen from Table 2, the steric factor dominates in reaction
of sulfonyl chloride 1 with N-alkylanilines, the more
branched is an alkyl substituent and the higher volume it
has, the lower is the reaction rate.15
Scheme 1.
Scheme 1
R = Me (a), Et (b), Bu (c)
The reaction kinetics (see Scheme 1) was studied using con-
ductometric method. Electrical conductivities of the work solu-
tions were measured on a Е7-14 LCR meter equipped with
ОК-9023 platinum ring electrode at a frequency of 1 kHz.
Arenesulfonylation of amines in water— organic solvents is
accompanied by hydrolysis of sulfonyl chloride, therefore the rate
of the change in the sulfonylation agent concentration provided
0
that concentration of an amine (cа ) is twofold higher than the
initial concentration of an acid chloride (с0), follows the equation
–dc/d = kaccac + khc = 2kac(c0 – x)2 + kh(c0 – x). (1)
Rate constants for the reaction of compound 2a and
benzenesulfonyl chloride (T = 298 K) in various organic
solvents (k•102/L mol–1 s–1) were determined15 being
1.82 0.02 for propan-2-ol, 13.22 0.06 for DMF,
1.35 0.02 for acetonitrile, 0.062 0.002 for ethyl methyl
Herein х is the change in the concentration of sulfonyl chlo-
ride by the time ; cа and с are current concentrations of an amine
and an acid chloride, respectively; kac is the rate constant for the
second order reaction (L mol–1 s–1); kh is the rate constant for
the acid chloride hydrolysis (s–1). The value of (с0 – х) was
calculated according the equation
Table 1. Rate constants for the reactions of anilines
and N-iso-butylanilines with compound 1 in propan-
2-ol (298 K)15
(c0 – x) = c0( – )/( – 0),
(2)
wherein 0, , and  are electrical conductivities of the reaction
mixture at the start time, at the time , and after completion of
the reaction, respectively.
The rate constant for hydrolysis of sulfonyl chloride 1 was
determined in the independent kinetic experiment, kh value was
calculated from 80—100 measurements of the electrical conduc-
tivity of the solution of the given agent by the Guggenheim
method:14
Ar
k•102/L mol–1 s–1
ArNHBui
ArNН2
4-MeC6H4
3-MeC6H4
4-EtC6H4
3-EtC6H4
Ph
3-MeО2СC6Н4
4-MeО2СC6Н4
4-EtО2СC6Н4
3.48 0.07
1.69 0.03
3.38 0.06
1.54 0.05
0.81 0.02
0.43 0.01
0.22 0.01
0.16 0.01
93.7 2.1
45.3 2.1
76.2 4.6
47.6 2.2
29.2 1.0
3.83 0.10
0.51 0.05
0.40 0.04
ln(i+1 – i) = A + khi.
(3)
Herein i and i+1 are the electrical conductivities of a solution
at the time i and i+1 = i + , A and  are constants.

Arenesulfonylation of N-alkylanilines
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 6, June, 2017
1001
from 30 up to 60 wt.%.14 Results on studying the effect of
composition of water—alcohol mixtures on kinetics of
reactions between N-alkylanilines 2a—c and sulfonyl
chlorides 1 are presented in Table 3.
Table 2. Rate constants for the reaction of amines
PhNHAlk with compound 1 in propan-2-ol (298 K)15
Alk
k•102/L mol–1 s–1
Reference to Table 3 shows that given the same propor-
tion of water in the system, the rate constants for the
amine 2b sulfonylation are higher by a factor of 1.5—2 over
the aqueous ethanol, thus correlating with polarity and
solvating capacity of these solvents. Reactivity of amines
rises in the row 2c < 2b < 2a, suggesting that steric factors
play a decisive role in kinetics of arenesulfonylation in
water—alcohol media as well as in the individual solvents.
As the molar fraction of water increases up to 0.63, a rever-
sion of reactivity of 2b and 2a is observed, allowing an-
ticipating more profound influence of steric effects of
a substituent in low-polarity media.
Rates of all the reactions rise on increasing the molar
proportion of water (Х1) in the system, however, changing
the solvent has a little effect on the rate constant, and
moving from organic solvents to water—alcohol mixtures
increases it by no more than five times.
Me
7.03 0.02
5.02 0.01
0.25 0.01
3.21 0.02
0.81 0.02
1.98 0.03
0.86 0.01
0.98 0.01
1.15 0.01
1.46 0.02
Et
Pri
Bu
Bui
Me2CH(CH2)2
PrCH(Me)CH2
Et2CHCH2
n-C7H15
n-C8H17
ketone, and 0.34 0.01 for acetone. Linear relationships
between logk and parameters of basicity (В) and electro-
philicity (Е) of a solvent were established:
lgk = –(14.57 0.73) + (0.05 0.01)В,
r = 0.99, s = 0.06, n = 3,
(4)
Results of kinetic study of reactions of N-methyl- (2a)
and N-ethylanilines (2b) with sulfonyl chloride 1 in aque-
ous solutions of 1,4-dioxane, THF, and acetonitrile are
given in Table 4.
lgk = –(10.36 2.55) + (0.18 0.06)E,
r = 0.91, s = 0.34, n = 4.
(5)
Significant decrease in the k value of arenesulfonylation
of the unsymmetric amines compared to that for aniline15
suggests that sterical hindrances due to the introduction
of an alkyl substituent into the amino group has stronger
influence on the reaction rate compared to its electronic
effect increasing the nucleophilicity of the N atom.
Activation parameters for the reaction 2b + 1 in aque-
ous 1,4-dioxane are presented in Table 5. The activation
barrier tends to decrease a little as the water percentage in
the system increases, which may be connected with pecu-
liarities of the solvation of an amine and the transition
state by the components of a binary solvent.
Relationships (4) and (5) suggest a significantly high-
er contribution of specific interactions in solution com-
pared to non-specific ones in kinetics of the reaction be-
tween amine 2a and PhSO2Cl. Similar effect is also typical
of reactions between areneamines and sulfonyl chlorides
in organic media.17
Addition of water into the system increases markedly
the rates of acylation reactions for many amino com-
pounds15,18 including anilines. For example, k value for
the reaction of aniline with 4-O2NC6H4SO2Cl increases
sevenfold upon changing the water content in 1,4-dioxane
Table 3. Rate constants15 for the reactions between N-alkylanilines 2a—c and com-
pound 1 in water-alcohol media (T = 298 K)
X1*
k•102/L mol–1 s–1
X1*
k•102/L mol–1 s–1
2a
2b
2b
2c
Water—ethanol
Water—propan-2-ol
0
—
—
0
15.00 0.01
—
10.60 0.03
—
16.02 0.01
21.50 0.06
3.21 0.02
5.21 0.04
7.45 0.04
9.45 0.04
11.20 0.08
13.10 0.25
0.12 (5)
0.22 (10)
0.31 (15)
0.39 (20)
0.52 (30)
0.63 (40)
0.72 (50)
0.79 (60)
16.4 0.1
20.0 0.1
34.1 0.2
37.5 0.2
41.5 0.3
43.5 0.4
53.8 0.6
85.5 0.6
11.4 0.6
15.3 0.2
21.2 0.6
28.1 0.2
41.2 0.8
55.7 0.6
—
0.15
0.27
0.37
0.45
0.59
—
* Molar fraction of water in a solvent (given in parentheses is weight percentage).

1002
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 6, June, 2017
Kochetova et al.
k•102/L mol–1 s–1
120
Table 4. Rate constants for the reactions between N-alkylanilines
2a,b and compound 1 (T = 298 K)
X1*
k•102/L mol–1 s–1
2a 2b
Water —1,4-Dioxane
X1*
k•102/L mol–1 s–1
3
2a
90
60
30
Water—THF
2
0.36
0.46
0.55
0.62
0.68
0.77
0.80
0.83
0.86
13.2 0.1
14.9 0.2
15.3 0.2 3.6 0.2
16.1 0.3 6.9 0.4
18.4 0.4 13.2 0.7
13.9 0.7
14.9 0.7
18.0 0.9
24 1
—
—
0.57
0.68
0.72
0.76
14.3 0.2
16.30.3
10.0 0.5
12.5 0.6
1
Water—acetonitrile
50 2
100 5
—
0.11
0.20
0.49
0.60
2.26 0.01
4
2.89 0.01
3.45 0.02
4.70 0.02
—
0.4
0.6
0.8
X1
* Molar fraction of water in a solvent.
Fig. 1. Relationships between k values for sulfonylation of
N-alkylanilines 2a,b with reagent 1 and composition of water-
organic solvents: 2b (1), water—ethanol; 2a (2), water—ethanol;
2b (3), water—1,4-dioxane; 2a (4), water—1,4-dioxane (X1 is
a molar proportion of water).
Table 5. Kinetic characteristics and activation parameters
for the reaction between N-ethylaniline 2b and compound 1
in aqueous 1,4-dioxane
*
Т/K
k•102
H
–S
298
(wt.%)
/L mol–1 s–1 /kJ m2o9l8–1 / kJ mol–1 К–1
of the steric factor on the reaction rate. It may be assumed
that the steric hindrance effect falls off with increase in
the medium polarity, and the electron-donating effect of
an alkyl substituent in the amino group begins to play
a decisive role, therefore the ratio of the rate constants
changes in favor of 2b in both binary systems. At the same
time, along with the change in solvent polarity and elec-
tronic effects of substituents, the reaction rate may be
influenced by the changes in the reagent solvation, occur-
ring upon changing the medium composition.
20
25
30
303
308
313
303
5.1 0.3
6.8 0.3
8.7 0.4
9.8 0.5
43 2
43 2
43 2
40 2
40 2
40 2
33 2
33 2
33 2
82 7
82 7
82 7
132 7
132 7
132 7
150 7
150 7
150 7
308 12.6 0.6
313 15.9 0.8
303 17.4 0.9
308 21.9 1.1
313 26.3 1.3
The data7,15—17 testify to the fact that specific solvation
of an amine has a predominant influence on the reaction
rate in arenesulfonylation as well as in the other acyl
transfer reactions involving amines, the solvation of a sulfo-
nating agent playing a small part. This conclusion is
consistent with the data on the reported thermochemical
studies.20
It should be noted that the existence of 1 : 1 Н-complexes
of aniline in the solvents of various nature including
1,4-dioxane,21 methanol, and water22—24 was confirmed
experimentally. In THF25,26 1 : 1 and 1 : 2 complexes were
detected. Formation of Н-complexes of aniline and a se-
ries of organic solvents is also confirmed by the quantum
chemistry methods.22,25,26
It is believed that similar to arylamines, N-alkylaryl-
amines exist in solution as amine—solvent molecular
complexes of various structure. In solution, a dynamic
equilibrium between solvatocomplexes takes place, which
can be shifted upon changes in a binary system composition.
Reactivity of solvatocomplexes is to depend on their structure
and stability. Since, as noted above, solvation of sulfonyl
chloride has no meaningful effect on the rate of sulfonyl-
ation of amines, so the rate constants of the reactions
* Weight percent of H2O in the solvent.
Sulfonylation rate constants rise with an increase in
the water content in all the binary solvents tested. The
most intensive rise of the k value (by nearly 30-fold) takes
place in the reaction 2b + 1 in the system water—1,4-di-
oxane, and the most high values of k are observed in
water-alcohol media (see Tables 3, 4 and Fig. 1). Monotonic
character of the relationship between k and the solvent
composition is in good agreement with the data on thermo-
chemical study of the water-alcohol and water-dioxane
mixtures:19 heats of mixing of components of these mix-
tures in the tested range of compositions also demonstrate
monotonic changes.
Of special attention is the character of relationship
between the rate constants for sulfonylation of 2a and 2b
and the composition of water-alcohol and water-ether
solvents (see Fig. 1). In low-polarity media (up to 20 wt.%
of water) the rate constant for the reaction 2a + 1 is
nearly 1.5 times higher than that for 2b + 1 reaction, what
is apparently connected with the predominant influence

Arenesulfonylation of N-alkylanilines
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 6, June, 2017
1003
Table 6. Quantum chemical parameters of solvatocomplexes of N-alkylanilines 2a,b (calculated using the
RHF/6-31G(d) method)
Complex
–Ek/kJ mol–1 ЕHOMO/eV
С2рz(N)2
2рz(N)
q(N)/e
r(N—H)/Å
2a•2Н2О
29
31
37
36
50
45
–7.95
–7.89
–7.86
–7.97
–7.73
–7.81
0.163
0.231
0.178
0.306
0.279
0.237
1.418
1.538
1.443
1.703
1.623
1.562
–0.832
–0.835
–0.861
–0.846
–0.859
–0.878
0.999
0.999
0.997
1.001
1.000
1.001
2a•H2O•EtOH
2a•H2O•1,4-dioxane
2b•2Н2О
2b•H2O•EtOH
2b•H2O•1,4-dioxane
Note. –Ek is the energy of complex formation calculated as a difference between total energies of complexes and
separate molecules forming the complexes, EHOMO is energy of the highest occupied molecular orbital of an
amine, С2рz(N) and 2рz(N) are contribution of the 2pz-orbital of the N atom of the amino group to the HOMO
of amine and its occupation, q(N) is an amount of charge on the N atom, r(N—H) is a N—H bond length in an
amine.
under consideration can be associated with the structure
and properties of solvatocomplexes of the mixed amines
with components of water-organic solvents.
Change in the reactivity ratio for 2a and 2b with an
increase in proportion of water in the binary solvent (see
Fig. 1) can also be explained within the framework of the
QSPR-approach. It should be noted that in all complexes,
a molecule of water (or one of the water molecules) is an
Н-donor forming hydrogen bond with lone-pair electrons
of the N atom, while the molecule of the second compo-
nent of a solvent or the second molecule of water presents
an H-acceptor forming a bond with the H atom of the
amino group.
One can assume that at small concentrations of water
in the binary systems, amines 2a,b exist mostly as mixed
complexes of 2b•H2O•Solv and 2a•H2O•Solv composition
(Solv is a molecule of ethanol or 1,4-dioxane). Judging
from higher values of 2рz(N) and С2рz(N)2, particles of
2b•H2O•Solv should be more reactive compared to those
of 2a•H2O•Solv. However the formation of a transition state
requires some energy to break the H-bond with the water
molecule which is an H-donor. Energy requirements will
be higher for more stable 2b•H2O•Solv complexes having
higher absolute values of energies of complex forma-
tion Eк (see Table 6). Because of this, reactivity of
2b•H2O•Solv in media with a high proportion of an or-
ganic component will be lower than that of 2a•H2O•Solv.
To elucidate the role of the specific solvation of
N-alkylanilines in kinetics of their arenesulfonylation
within the framework of the QSPR-approach, we carried
out quantum-chemical modeling of solvatocomplexes 2a
and 2b with water, 1,4-dioxane, and EtOH having
the following compositions: 2a•2Н2О, 2a•H2O•EtOH,
2a•H2O•1,4-dioxane, 2b•2Н2О, 2b•H2O•EtOH, and
2b•H2O•1,4-dioxane. Calculations were performed using
Firefly 7.1G software.27 Selected data of calculations are
given in Table 6.
As can be seen from Table 6, energies of complex for-
mation (Eк) for all solvatocomplexes have high negative
values, suggesting stability of these particles and high
probability of their existence in solution.
Comparison of geometrical and charge characteristics
of reaction centers, i.e. imino groups of the solvated amines
with the rate constants for the reactions 2a + 1 or 2b + 1
showed no correlation. Earlier we have found that acylation
of aliphatic amines and -amino acids presents orbital-
controlled reactions, wherein the values of occupation
density (2рz(N)) and squared contributions of 2рz-АО of
the nitrogen atom in HOMO (С2рz(N)2) can serve as de-
scriptors of reactivity of amino compounds and their
molecular compexes with the solvent components.3,17,18
Therefore, kinetic data on reactions between N-alkyl-
anilines 2a—c with sulfonyl chloride 1 and characteristics
of the nitrogen 2рz-АО in solvatocomplexes of nitrogen
2a and 2b were compared. It was found that the experi-
mentally observed increase in the k value for arenesulfo-
nylation in aqueous alcohols by contrast to aqueous
1,4-dioxane (see Fig. 1, Tables 3, 4) correlates with
higher values of occupancies and squared contributions of
the nitrogen 2рz-АО to HOMO in complexes of amines
with H2O and EtOH as compared to complexes of amines
with H2O and 1,4-dioxane (see Table 6).
Solv is the molecule of ethanol or 1,4-dioxane.
As the content of water rises, equilibrium in solution
can shift towards 2b•2H2O and 2a•2H2O complexes.
Dihydr ates 2b should be more reactive than dihydrates 2a
having lower values of С2рz(N)2 and 2рz(N). As a result,
with increasing the proportion of water in both binary

1004 Russ. Chem. Bull., Int. Ed., Vol. 66, No. 6, June, 2017
Kochetova et al.
Table 8. Results of the quantum chemical modeling
of the interaction between molecules of N-methyl-
aniline 2a and DMSO (RHF/6-31G(d) method)
systems, the rate constant for the reaction 2b + 1 rises
compared to the k value of 2a arenesulfonylation. Since
the complexes 2b•2H2O are the most reactive among all
modeled structures (see Table 6), at Х1 = 0.8 the rate
constant for the reaction 2b + 1 in aqueous 1,4-dioxane
becomes higher than that in aqueous ethanol.
Parameter
2a
2a•DMSO
q(N)/e
–0.767
0.997
–7.76
1.758
0.372
–0.821
0.998
–7.07
1.769
0.425
r(N—H)/Å
EHOMO/eV
2рz(N)
Thus, an inversion of the ratio of the rates of reactions
between sulfonyl chloride 1 and 2b or 2a, taking place on
change in the composition of binary solvents, is associ-
ated with an effect of several factors. In the media enriched
with an organic component (1,4-dioxane or alcohol), reac-
tivity of amines is influenced mainly by steric hindrances
caused by ethyl group of amine 2b, as well as by high energy
consumption for desolvation of the molecule of this amine
before the transition state formation, lowering the reactivity
of the above amine compared to that of 2a. With increase in the
water content in the system, reactive dihydrates 2b are formed
whereby the sulfonylation rate for 2b exceeds that for 2a.
Since the rates of reactions between N-alkylanilines
and arenesulfonyl chlorides in the tested solvents are
moderate, the search for a catalyst is necessary. Addition
of DMSO to a solution was found to increase the rate of
the reaction 2a + 1, the less is the DMSO concentration
(сDMSO), the higher is the reaction rate (Table 7). The ob-
served experimental fact can apparently be attributed to
the side reactions proceeding with equimolar amounts of
DMSO and sulfonyl chloride 1.
Catalytic effect of DMSO can be accounted for its
ability to activate N-methylaniline (2a) due to the transfer
of the amine proton to the O atom of the S=O moiety.
This proposal is confirmed by the data on the quantum
chemical modeling of interaction between molecules of
2a and DMSO (Table 8). Results of calculations demon-
strated that formation of a hydrogen bond between the
amino group hydrogen atoms and the DMSO oxygen atom
increases the reactivity of the system 2a — DMSO both
due to an increase in the negative charge on the N atom,
and an increase in the values of the HOMO energy, oc-
cupancies (2рz(N)), and squared contributions of the
nitrogen 2рz-АО to the HOMO (С2рz(N)2).
С2рz(N)2
chemical calculation of PES for the reaction between
amine 2a and PhSO2Cl in the gaseous phase. The calcula-
tions were performed in the supermolecular approximation
using DFT//B3LYP/6-311G(d,p) method. Three-di-
mensional PES was calculated in coordinates of r(S—N)
distance ranging from 1.5 to 4.5 Å, and an attack angle of
a nucleophile (amine) on the (СAr—S—N) sulfonyl group
ranging from 90 (frontal attack ) to 180 (axial attack)
with a step of 10.
The above parameters were recorded in each point of
PES, and geometry of the reacting system of molecules
was optimized. Basing on the results of analysis of the PES
obtained, the position of the saddle point corresponding
to the reaction transition state (TS) was determined.
Consistency between the structure found and activated
reaction complex was confirmed by the presence of one
imaginary frequency in the vibrational spectrum. The PES
obtained is shown in Fig. 2.
There is a single saddle point on the contour map,
answering to the reaction TS and lying on the path of
minimal energy which corresponds to the frontal attack of
nucleophile on the sulfonyl reaction center at an angle of
100. Throughout the interaction this angle varies only
slightly reaching 96 in the TS and increasing up to 110
in the sulfamide reaction product. Reaction products are
formed at r(S—N)  1.8 Å. At the same time an abstraction
of HCl takes place, this being testified by the lengths of
the breaking N—H and S—Cl bonds which are equal to
1.027 and 2.828 Å in the TS and constitute 1.931 and
4.272 Å in the product, respectively, as well as by the length
of the Н—Cl bond being formed: the latter is 2.062 Å in
the TS, and 1.321 Å in the product. In this case the N—H
and S—Cl bonds become coplanar, as evidenced by the
value of the torsion angle Cl—S—N—H which is equal to
7.03in the TS, and to 0.61 in the product.
To elucidate the reaction mechanism for arenesulf-
onylation of N-alkylanilines we performed the quantum
Table 7. Rate constants for the reaction between
N-methylaniline 2a and compound 1 in water—
1,4-dioxane mixture (proportion of H2O is
35 wt.%) with addition of DMSO
Thus, the reaction proceeds without formation of in-
termediates, with a single TS at r(S—N) = 2.6 Å according
the bimolecular nucleophilic substitution (SN2) mecha-
nism, what is in an agreement with the results of modeling
of other acyl transfer reactions.28
Resuts of calculation of the activated complex (АC) of
the reaction are given in Table 9 and in Fig. 3.
СDMSO
k•102
/mol L–1
/L mol–1 s–1
0
11.4 0.3
170 5
96 3
0.002
0.006
0.009
0.01
62 2
As can be seen from Fig. 3 and Table 9, AC of the above
reaction has a structure similar to a tetragonal pyramid.
50 2

Arenesulfonylation of N-alkylanilines
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 6, June, 2017
1005
/deg
b
a
E/Hartree
180
–1567.40
160
140
120
–1567.44
–1567.48
–1567.52
–1567.56
/deg
160
140
120
100
r(S—N)/ Å
100
1.5
2.5
3.5
TS
1.5
2.5
3.5
4.5 r(S—N)/ Å
Fig. 2. Three-dimensional view (a) and contour map (b) of PES for the reaction between N-methylaniline 2a and PhSO2Cl (direction
of attack of molecule 2a changes from the frontal to the axial one);  is an angle of attack (СAr—S—N),  is a transition state (TS)
for the reaction.
This is consistent with the literature data29 from which it
follows that in the case of frontal attack of a nucleophile
the TS is formed having the structure of tetrahedral pyra-
mid with the S atom in its base.
The value of the activation energy of the reaction un-
der investigation calculated as a difference in the energies
of formation of the AC and reactants proved to be
112.8 kJ mol–1; this high value can be explained by the
fact that the process was modeled for the gaseous phase.
According to the literature data,28,30 modeling the acyl
transfer reactions in view of the influence of solvation of
amino compounds decreases significantly the reaction
energy barriers.
In conclusion, we have studied kinetics of arenesulfo-
nylation of N-alkylanilines PhNHAlk (2a—c) in binary
mixtures of water and ethanol, propan-2-ol, 1,4-dioxane,
THF, and acetonitrile, having a variable composition.
Reactivity of amines rises along the row of 2c < 2b < 2a
N
S
2.600 Å
2.828 Å
Cl
Fig. 3. Structure of activated complex of the reaction between
N-methylaniline (2a) and PhSO2Cl.
Table 9. Geometrical and energy characteris-
tics of the activated complex of amine 2a with
PhSO2Cl
(Bu < Et < Me) suggesting the predominant role of steric
factors in kinetics of arenesulfonylation. The growth of the
rate constants for arenesulfonylation of amines 2a—c,
observed on increasing the content of water in all tested
binary systems was established. Effect of nature and com-
position of the binary solvents on reactivity is explained
using quantum chemical modeling data on the basis
of specific solvation of the mixed amines in solution.
According to the calculations, sulfonylation of amino
compounds in the gaseous phase proceeds by the bi-
molecular concerted mechanism.
Parameter
Value
r(S—N)/Å
r(S—Cl)/Å
P(S—N)
2.600
2.828
0.19
P(S—Cl)
0.31
C
Ar—S—N/deg
96
–0.61
–112.8
Cl—S—N—H/deg
Еact/kJ mol–1
Note. P is a bond order.

1006 Russ. Chem. Bull., Int. Ed., Vol. 66, No. 6, June, 2017
Kochetova et al.
17. L. V. Kuritsyn, N. A. Khodonina, Izv. Vysshih Uchebnykh
Zavedeniy. Khimiya I khimicheskaya tekhnologiya [Transac-
tions of Chemistry and Chemical technology], 1987, 30, 52
(in Russian).
18. L. B. Kochetova, N. V. Kalinina, L. V. Kuritsyn, T. P. Kustova,
Butlerov Comm., 2014, 37, 33.
The work was financially supported by the Ministry of
Education and Science of the Russian Federation.
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Received February 28, 2017;
in revised form April 6, 2017