Physicochemical properties of 4,5-(aryl,alkyl)-3-substituted 2-aminothiophenes sulfonyl derivatives

Article abstract of DOI:10.1134/S1070363217030094

Physicochemical properties of 4,5-(aryl, alkyl)-3-substituted 2-sulfonylaminothiophenes have been studied. The effect of the nature of the substituents in the thiophene ring on acid-base properties, solubility, and chemical stability was investigated.

Full text of DOI:10.1134/S1070363217030094

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 3, pp. 414–419. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © L.G. Chekanova, K.O. Manylova, P.T. Pavlov, А.N. Vasyanin, S.N. Shurov, О.А. Maiorova, 2017, published in Zhurnal Obshchei
Khimii, 2017, Vol. 87, No. 3, pp. 405–410.
Physicochemical Properties of 4,5-(Aryl,alkyl)-3-substituted
2-Aminothiophenes Sulfonyl Derivatives
L. G. Chekanovaa*, K. O. Manylovaa, P. T. Pavlovb,
А. N. Vasyaninb, S. N. Shurovb, and О. А. Maiorovaa
a Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences,
ul. Akademika Koroleva 3, Perm, 614013 Russia
*е-mail: larchek.07@mail.ru
b Perm State National Research University, Perm, Russia
Received September 22, 2016
Abstract—Physicochemical properties of 4,5-(aryl, alkyl)-3-substituted 2-sulfonylaminothiophenes have been
studied. The effect of the nature of the substituents in the thiophene ring on acid-base properties, solubility, and
chemical stability was investigated.
Keywords: sulfonyl derivatives of aminothiophenes, acid-base properties, solubility, chemical stability
DOI: 10.1134/S1070363217030094
Earlier, we have studied a series of ethyl 2-aryl-
(methyl)sulfonylamino-4,5,6,7-tetrahydro[b]-thiophene-
3-carboxylates as reagents for ionic flotation of non-
ferrous metals [1, 2]. Considering all properties, for
further investigation we have chosen ethyl-{2-mesyl-
(tosyl)amino-4,5,6,7-tetrahydro-benzo[b]thiophene}-3-
carboxylates. We planned to investigate the variations
in the physicochemical properties of these compounds
depending on the nature of the functional group in the
position 3, as well as on substituents in the positions 4
and 5 of the thiophene ring. For this purpose we have
synthesized 2-(aryl, methyl)-sulfonylamino-4,5,6,7-tetra-
hydrobenzo[b]-3-substituted thiophenes 1–5 and ethyl-
2-tosylamino-4,5-(aryl, alkyl)-thiophene-3-carboxylates
6–11 (Scheme 1).
Compounds 1, 3, 4 were obtained by the reaction of
the corresponding thiophenes with tosyl chloride. Com-
pounds 2 and 5 were obtained by the hydrolysis of the
corresponding esters with aqueous-alcohol-dioxane
solution of NaOH. We failed to isolate the products
with the amide or substituted amide group from the
synthesis of 2-mesylamino-4,5,6,7-tetrahydrobenzo[b]-
3-substituted thiophenes because of the formation of a
large amount of side products. Compounds 6–11 were
obtained by the reaction of the corresponding thio-
phenes with tosyl chloride, as we described earlier [1].
The obtained compounds are crystalline products
(Table 1).
The structure of the synthesized compounds was
proved by IR and NMR spectra. The IR spectra of
Scheme 1.
R1
O
O
R2
OC2H5
O
O
S R1
S
CH3
NH
R2
NH
S
S
O
O
1_5
6_11
R1 = Tol, R2 = OEt (1), OH (2), NH2 (3), NHPh (4); R1 = Me; R2 = OH (5); R1 = Ph, R2 = Ph (6); R1 = Bn, R2 = Ph (7); R1 =
Me, R2 = Ph (8); R1 = Me, R2 = Me (9); R1 = Ph, R2 = Me (10); R1 = Ph, R2 = Et (11).
414

PHYSICOCHEMICAL PROPERTIES OF 4,5-(ARYL,ALKYL)-3-SUBSTITUTED
415
Table 1. Physicochemical characteristics of compounds 1–11
compounds 1–5 contain absorption bands of stretching
vibrations of the secondary amino group at 3117–
3312 cm–1; ester 1 (1657 cm–1), carboxyl 2 (1627 cm–1),
5 (1650 cm–1); primary 3 (1660 cm–1) and secondary
amide groups 4 (1640 cm–1). The absorption bands of
symmetric and asymmetric stretching vibrations of the
SO2 group appear in the range 1153–1169 and 1323–
1340 cm–1. Besides, the IR spectrum of 2 contains a
separate band of the carboxyl hydroxy group at
3300 cm–1. The absorption band of the NH2 group in
the spectrum of compound 3 appears at 3300 cm–1. In
the spectrum of compound 4 the band of the anilide
group appears at 3363 cm–1. In the IR spectra of
compounds 6–11 the absorption bands are observed of
the stretching vibrations of secondary amino group
(3147–3312 cm–1) and of ester group (1656–1677 cm–1);
the absorption bands of symmetric and asymmetric
stretching vibrations of SO2 group appear in the range
1156–1165 and 1327–1340 cm–1.
1Н NMR spectra of solutions of compounds 1–11 in
DMSO-d6 contain singlet signals of the NH group
protons (10.22–10.82 ppm) and the protons of the
aromatic ring at the SO2 group (7.09–7.82 ppm). In the
spectra of compounds 1–5 the multiplets of the
methylene group protons 5,6-(CH2)2 (1.65–1.70 ppm)
and 4,7-(CH2)2 group (2.51–2.63 ppm) are observed,
and for compound 5 also a singlet of the methyl group
appears (3.14 ppm). The OEt group in 1 is observed as
a quartet at 4.24 ppm (СН2О) and a triplet at 1.27 ppm
(СН3). In the spectra of 2 and 5 the carboxyl and
sulfamide protons give a wide combined signal at
10.79 and 10.32 ppm, respectively. The primary amide
protons in the spectrum of compound 3 resonate as a
wide singlet at 7.14 ppm. The anilide proton in the
spectrum of compound 4 resonates at 9.70 ppm. In the
spectra of compounds 6–11 the signals of aromatic
protons appear in the range 6.87–7.52 ppm, the OEt
group is seen as a quartet at 3.80–4.23 ppm (СН2О)
and a triplet at 0.78–1.31 ppm (СН3).
рKа
Comp.
no.
mp, °C
Rfа
рKа1
рKа2
1
2
125–127
189–191
201–203
187–189
172–174
141–144
108–110
120–123
91–92
0.53
0.49
0.64
0.53
0.30
0.80
0.73
0.81
0.73
0.74
7.77±0.05
4.74±0.07
6.86±0.04
4.19±0.08
4.68±0.06
6.48±0.07
7.02±0.05
7.28±0.05
7.85±0.08
7.16±0.06
–
3
4
–
5
8.18±0.07
6
7
8
9
10
11
110–112
117–119 0.87/0.41b 7.07±0.05
a
Eluent – benzene : ether = 10 : 1 (1, 6–11); benzene : ether = 5 : 1
(2); ethyl acetate : benzene = 2 : 1 (3–5).
Eluent – benzene.
b
pounds 2–5 are readily soluble in diluted solutions of
KOH and in ethanol, so, the use of these solutions is
possible in flotation processes. For extraction the
solutions are suitable of compounds 1, 6–11 with the
ester group in position 3 of the thiophene ring due to
their moderate solubility in p-xylene and chloroform.
Compounds 1–11 are NH-acids. Ionization in
alkaline media can be represented by Scheme 2. For
compounds 2, 4, 5 both elimination of the NH proton
(Scheme 2) and the formation of the salt on the
carboxyl group in the position 3 of the thiophene ring
is possible (Scheme 3).
For compounds 6–11, as well as for 1 and 3, the
constants of acid dissociation were measured by the
method of potentiometric titration (Table 1). On the
curve of conductometric titration of compounds 2, 4, 5
with alkali, two inflection points are observed (Fig. 1),
apparently corresponding to two dissociation steps.
All compounds, except 5, are poorly soluble in
isoamyl alcohol, hexane, and water (Table 2). Com-
Scheme 2.
O
O
R1
OC2H5
O
R1
R2
OC2H5
O
KOH
H+
+ H2O
_
R2
N
S
R1
S
R1
NH
S
S
K+
O
O
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 3 2017

416
CHEKANOVA et al.
Solubility, mol/L (g/L)
Table 2. Solubility of compounds 1–11
Comp.
EtOH,
×103
25.0
(9.60)
22.8
(8.0)
7.3
(2.55)
9.9
(4.2)
100.0
(27.6)
7.0
0.1 M KОН,
×104
H2O,
×104
4.0
(0.16)
8.5
(0.30)
5.7
(0.22)
hexane,
×103
p-xylene,
i-АmOH,
chloroform,
×102
no.
×102
×102
1
9.0
7.0
(2.64)
1.7
(0.60)
0.01
(0.01)
68.0
(258.60)
0.43
(1.50)
0.4
(1.30)
0.5
(2.20)
0.4
2.1
(7.83)
1.5
(5.30)
0.2
(0.70)
0.8
(3.30)
2.8
195.0
(741.5)
5.3
(18.70)
5.3
(18.60)
37.4
(159.30)
10.2
(0.33)
312.5
(10.97)
720.0
(25.23)
162.5
(6.92)
625.0
(17.19)
0.2
2
3
4
Insoluble
Insoluble
5
29.0
(0.80)
8.0
4.4
(1.20)
1.7
(1.20)
15.9
(7.80)
0.5
(28.00)
83.9
6
(3.20)
0.8
(0.01)
0.5
(0.40)
Insoluble
(0.80)
0.8
(76.00)
22.7
(2.60)
Insoluble
(400.00)
99.6
7
(0.40)
11.0
(4.60)
25.0
(0.03)
0.4
(0.02)
45.0
(0.40)
4.0
(1.80)
5.0
(111.40)
38.6
(160.20)
70.9
(489.00)
118.5
(492.00)
140.0
8
9.6
(0.40)
Insoluble
0.9
(3.80)
2.7
9
(8.99)
20.7
(8.60)
13.0
(1.59)
13.0
(0.54)
2.0
(1.80)
6.7
(2.80)
8.6
(250.20)
54.9
(228.00)
68.9
(9.67)
1.3
(5.33)
1.4
(494.70)
147.5
(613.00)
107.8
10
11
4.8
(0.20)
Insoluble
(5.60)
(0.09)
(3.70)
(296.00)
(6.00)
(463.00)
In the electron absorption spectra with the increase
By potentiometric titration two acid dissociation
constants were determined for compound 5 (Table 1).
For compound 2 and 4 we failed to calculate the value
of the second constant from the experiment.
of pH of solutions of 2 and 5 an increase in the
intensity of the band with the maximum at 225–
230 nm is observed and a band appears at 280–
290 nm, which can be tentatively assigned to the
superposition of the two ionized forms. The presence
of two isosbestic points in the spectrum of compound 2
(Fig. 2) proves the equilibrium of three forms in the
solution. In the case of compound 4 with the increase
in рН three absorption bands are observed in the
spectrum with the maxima at 235, 335, and 220 nm
(рН > 11).
To determine the site of primary deprotonation we
have calculated the total energies (Еtot) of compounds
1–5 and the corresponding anions in gas phase using
the B3LYP/6-311G(d) method (Table 3). The com-
parison of the energies of the anions shows that for
compound 2 the О-anion 2b is by 53.8 kJ/mol more
stable than the N-anion 2a. The ∆Е value for the pair 2
Scheme 3.
O
O
OH
O_ K+
O
2KOH
+ 2H2O
O
S
2H+
_
R1
S
R1
NH
N
S
S
K+
O
O
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 3 2017

PHYSICOCHEMICAL PROPERTIES OF 4,5-(ARYL,ALKYL)-3-SUBSTITUTED
417
w, μS/cm
А
400
350
300
250
200
150
100
50
0
λ, nm
VNaOH, mL
Fig. 2. Electron absorption spectra of aqueous-alcohol
solution of 2-tosylamino-4,5,6,7-tetrahydrobenzo[ ]thiophene-3-
Fig. 1. Conductometric titration of 2-mesylamino-4,5,6,7-
tetrahydrobenzo[b]thiophene-3-carboxylic acid 5. рН ~ 5,
V0 = 76 mL, m5 = 0,2573 g; cKОН = 0.094 mol/L.
b
carboxylic acid 2 at рН (1) 5.1; (2) 6.7; (3) 9.2; (4) 11.7;
c2 = 10–5 mol/L.
and 2b is 0.5209 a.u., while for compound 5 and its
О-anion 5b it increases to 0.5303 a.u. suggesting a
lower acidity of compound 5 as compared to
compound 2 in the gas phase.
To confirm the course of ionization of compounds
2 and 5 we have synthesized a model compound,
4,5,6,7-tetrahydrobenzo[b]-3-thiophenecarboxylic acid,
lacking the second site of ionization. The рKа value
Table 3. Electronic characteristics of compounds, B3LYP/6-311G(d)
Total
energy,
Hartrees
Total
energy,
Hartrees
Comp.
no.
Comp.
no.
Structure
COOH
Structure
_
–1172.2068
–1751.7717
2
3b
CONH
NHSO2C6H4CH3-p
COOH
S
S
NHSO2C6H4CH3-p
COOH
S
S
–1171.6654
–1171.6859
–1541.1089
–1540.5672
2а
5
_
NHSO2CH3
NSO2C6H4CH3-p
COOH
O
2b
5а
O_
_
NSO2CH3
H
N
S
S
S
SO2C6H4CH3-p
CONH2
_
–1752.3279
–1540.5786
3
5b
COO
NHSO2C6H4CH3-p
CONH2
S
S
NHSO2CH3
–1751.8039
3а
_
NSO2C6H4CH3-p
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 3 2017

418
CHEKANOVA et al.
Scheme 4.
NH2
O
O
NHC6H5
O
OH
H2O
+
O
S
S
R1
R1
NH
NH
S
S
O
O
determined by potentiometric titration is 5.32. For
comparison, рKа for compounds 2 and 5 are 4.74 and
4.68, respectively, and for 1 (having one center of
ionization according to Scheme 2) it is 7.77 (Table 1).
These data prove the assumption that ionization of
thiophenes 2 and 5 occurs first on the carboxyl and
later on the sulfonamide group.
The analysis of the 1Н NMR spectra of solutions of
compound 4 in DMSO-d6 revealed that in comparison
with the neutral solution, in the alkaline solution the
signal of the sulfonamide proton at 10.27 ppm is
retained whereas the signal of the anilide proton at
9.70 ppm disappears. Also signals appear at 11.53 and
4.4 ppm, whose intensity increases with the NaOH
concentration. It is presumable that in the alkaline
medium compound 4 is hydrolyzed (Scheme 4). The
signals at 11.53 and 4.4 ppm may be assigned, respec-
tively, to the protons of the carboxyl group and aniline.
EXPERIMENTAL
IR spectra were recorded on a IFS-66/S Fourier
1
spectrometer (Bruker, Germany). H NMR spectra
were registered on
a
MERCURY plus 300
spectrometer (Varian, USA) in DMSO-d6, internal
reference HMDS. Melting points were determined on a
PTP instrument in capillaries. Elemental analysis was
performed on a CHNS-932 analyzer (LECO Co.,
USA). Conductometric titration was performed on an
Anion 4100 conductometer. UV spectra were registered
on a SF-2000 spectrophotometer, refraction indices
were measured on an IRF-22 refractometer. The
solubility of the products was determined by known
procedures using the methods of gravimetry [5, 6],
spectrophotometry [5] and refractometry [7]. The
reactions were monitored by TLC on Silufol UV-254
plates in appropriate systems of mobile phases, and
developed by iodine vapor.
The hydrolysis of compound 4 was proved by the
method of TLC (Rf = 0.50, benzene:ether = 5 : 1) with
2-tosylamino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-
carboxylic acid (Rf = 0.35) and aniline (Rf = 0.42) as
authentic samples.
The content of metal ions in solutions was determined
on an atomic absorption spectrometer iCE 3500 with
flame atomization (Thermo Fisher Scientific, USA).
Acid dissociation constants were determined by the
methods of spectrophotometry [8] and potentiometry
[9]. pH values and EMF of solutions were measured
on a I-160М ionomer with glass and silver chloride
electrodes. pH values were corrected for the presence
of ethanol; the correction was required to calculate the true
concentration of hydrogen ions as described in [10, 11].
For compound 3 the possibility is presumable of a
proton addition due to the presence of a free lone
electron pair on nitrogen of the NH2 group. However,
potentiometric titration with НСl solution did not
prove the formation of the protonated form.
Spectrophotometrically it was found that
compounds 1–3 and 5–11 are stable in 0.1 М KОН
solution at 60°С for 4 h, and at 20°С for 1 day. The
substituents in the positions 4 and 5 of the thiophene
ring do not affect the stability.
The content of the main compound was determined
by potentiometric [3] and conductometric titration [4];
it was no less than 97%. For conductometric titration,
the specimen of 0.2–0.3 g was dissolved in the mixture
of water and EtOH (1 : 3) and titrated with 0.1 М KOH
solution. The assay was determined from the plot of
electroconductivity of the solution versus the titrant
volume by the formula
The comparison of the properties of the sulfonyl deriva-
tives of aminothiophenes allows a conclusion that the
reagents with the ester group in the position 3 of the
thiophene ring 1, 6–11 are of the most interest for further
investigations as flotoreagents for non-ferrous metals
due to their moderate solubility in aqueous alkali and
in alcohol, as well as in a number of organic solvents.
c, % = (VME)/(m×10),
(1)
where V is the titrant volume at the point of first
inflection, mL; М is concentration of KOH titrant
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 3 2017

PHYSICOCHEMICAL PROPERTIES OF 4,5-(ARYL,ALKYL)-3-SUBSTITUTED
419
Russ. J. Appl. Chem., 2010, vol. 83, no. 8, p. 1475. doi
10.1134/S107042721008029X
solution, mol/l; m is the mass of specimen, g; E is
equivalent equal to molecular mass of the compound.
The hydrolytic stability was investigated spectrophoto-
metrically by the procedure described in [5].
4. Radushev, A.V., Chekanova, L.G., Gusev, V.Yu., and
Sazonova, E.A., Russ. J. Anal. Chem., 2000, vol. 55,
no. 5, p. 445. doi 10.1007/BF02757481
Quantum-chemical calculations with full geometry
optimization were performed on a supercomputer PSU-
Tesla of the Center of parallel and distributed
calculations of the Perm State National Research
University using Firefly program package [12].
5. Chekanova, L.G., Radushev, A.V., Lesnov, A.E., and
Sazonova, E.A., Russ. J. Gen. Chem., 2002, vol. 72,
no. 8, p. 1233. doi 10.1023/A:1020875628798
6. Analiticheskaya khimiya. Khimicheskie metody analiza
(Analytical Chemistry. Chemical Methods of Analysis),
Petrukhin, O.M., Ed., Moscow: Khimiya, 1992.
ACKNOWLEDGMENTS
7. Pilipenko, A. and Pyatnitskii, I., Analiticheskaya khimiya
(Analytical Chemistry), Moscow: Khimiya, 1990, book 1.
This work was financially supported by the Russian
Foundation for Basic Research (grant 14-03-00606-а).
8. Bernshtein, I.Ya. and Kaminskii, Yu.L., Spektrofoto-
metricheskii analiz v organicheskoi khimii (Spectro-
photometric Analysis in Organic Chemistry),
Leningrad: Khimiya, 1986.
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