Azomethine derivatives on the basis of 5-formyl-2,2′-bithienyl and 5-formyl-2,2′-dithienyl sulfide

Article abstract of DOI:10.1023/A:1023064507442

Six azomethine derivatives of 2,2′-dithienyl sulfide and five of 2,2′-bithienyl have been synthesized for the first time.

Full text of DOI:10.1023/A:1023064507442

Chemistry of Heterocyclic Compounds, Vol. 39, No. 1, 2003
AZOMETHINE DERIVATIVES ON THE
BASIS OF 5-FORMYL-2,2'-BITHIENYL
AND 5-FORMYL-2,2'-DITHIENYL SULFIDE
N. A. Korchevin, N. V. Russavskaya, E. P. Levanova, E. N. Sukhomazova, and E. N. Deryagina
Six azomethine derivatives of 2,2'-dithienyl sulfide and five of 2,2'-bithienyl have been synthesized for
the first time.
Keywords: azomethines, amines, 5-formyl-2,2'-bithienyl, 5-formyl-2,2'-dithienyl sulfide.
Azomethines of the thiophene and 2,2'-bithienyl series are promising antiseptic preparations [1,2].
Similar compounds are readily formed on condensing primary aromatic amines with appropriate aldehydes
[2,3]. However there are no literature data on the preparation of azomethines of the 2,2'-dithienyl sulfide series.
The introduction of a sulfur atom between the thiophene rings may possibly increase the conformational
mobility of the latter, which may be displayed in specific physicochemical properties of compounds based on
2,2'-dithienyl sulfide. Azomethines are also starting materials for the synthesis of heterocyclic compounds [4],
and extending their variety is a promising undertaking.
We have synthesized for the first time a series of azomethines from 5-formyl-2,2'-dithienyl disulfide (1),
1
which were characterized by IR and H NMR spectra. Azomethine analogs of 2,2'-bithienyl were synthesized
and characterized for comparison. The majority of these were also obtained for the first time.
The reactions of aldehydes 1,2 with amines 3 were effected in the absence of solvent (in the case of
liquid amines) or in ethanol. The exothermic reaction was carried out without supplying heat, but in certain
cases a little heating (40-50°C) enabled an increase in the yield of the desired product (Table 1).
RNH2
3
O
NR
S
S
S
S
S
S
H
H
4
1
RNH2
3
O
NR
S
S
S
S
5
H
H
2
3a, 4a R = Ph; 3b– 5b R = 4-BrC6H4; 3c– 5c R = PhCH2; 3d– 5d R = 4-MeC6H4;
3e– 5e R = 4-HOC6H4; 3f– 5f R = HOCH2CH2; 3g, 5g R = 2-ClC6H4
N
N
N
3h
, 5h R =
__________________________________________________________________________________________
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
Irkutsk 664033, Russia; e-mail: vlad@irioch.irk.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii,
No. 1, pp. 60-64, January, 2003. Original article submitted April 21, 2000.
0009-3122/03/3901-0056$25.00©2003 Plenum Publishing Corporation
56

TABLE 1. Synthesis Conditions and Physicochemical Characteristics of Azomethines 4 and 5*
Found, %
——————
Com-
Empirical
formula
Calculated, %
Reaction temp. °C
mp, °С*3
Yield, %
70
pound
C
H
N
Hal
—
S
4a*2
C15H11NS3
60.61
59.80
3.75
3.65
4.49
4.65
31.51
31.89
20-25
62-63
C15H10BrNS3
C16H13NS3
48.00
2.60
3.64
21.61
21.04
25.12
40-45
40
71-72
42
85
90
70
80
63
78
72
62
97
54
45
55
4b
4c
4d
4e
4f
47.38
2.63
3.69
25.27
61.08
60.95
4.02
4.13
4.40
4.44
—
—
—
—
30.46
30.48
C16H13NS3
61.55
4.12
4.24
29.83
20-25
45-50
20-25
50
84-85
60.95
4.13
4.44
30.48
C15H11NOS3
C11H11NOS3
C15H10BrNS2
C16H13NS2
56.26
56.78
3.58
3.47
4.45
4.42
29.86
30.28
136-137
47-48
49.41
4.14
5.23
34.85
49.07
4.09
5.20
35.69
52.15
51.72
3.01
2.87
3.76
4.02
23.65
22.99
18.58
18.39
117-118
56-57
5b
5c
5d
5e
5f
68.28
4.57
4.77
—
—
—
—
22.77
20-25
20-25
50-55
20-25
25-30
30-40
67.84
4.59
4.95
22.61
C16H13NS2
67.96
67.84
4.82
4.59
4.80
4.95
21.90
22.61
119-120
231-232
64-65
C15H11NOS2
C11H11NOS2
C15H10ClNS2
C11H8N4S2
63.58
3.91
4.75
22.19
63.16
3.86
4.91
22.46
56.03
55.77
4.67
4.64
5.48
5.91
26.97
27.00
60.10
3.50
4.67
12.26
11.70
—
21.02
74-75
5g
5h
59.31
3.29
4.61
21.09
50.62
50.77
3.00
3.15
20.55
21.5
24.24
24.62
165-166
_______
* Solvent was ethanol for compounds 4a,b,d,e 5b,d,e,h.
*2 Yield was 80% when carrying out the reaction at 40-45°C.
*3 According to [2], compound 5d has mp 126-128°C, and 5e 228-229°C.

1
TABLE 2. The IR and H NMR Spectral Characteristics of Azomethines 4
and 5
δ, ppm, J (Hz)
Com-
pound
IR spectrum, cm-1
N–CH2
(characteristic frequencies)
HAr
CH=N
CH2–OH(СН3)
(ОН)
3070 (w), 2960 (w),
7.44-6.95 (m)
8.38 (s)
4a
4b
4с
2860 (w), 1600 (s), 1580 (s),
1490 (s), 1450 (m), 1420 (s)
3060 (w), 2910 (w),
7.48-6.98 (m)
7.36-6.84 (m)
8.36 (s)
2850 (w), 1600 (s), 1570 (s),
1480 (s), 1420 (s)
3070 (w), 3020 (w),
8.25 (t,
4.71 (d,
2920 (w), 2860 (w),
J = 1.46) J = 1.46)
2810 (w), 1620 (s), 1500 (m),
1450 (m), 1420 (s)
3080 (w), 3010 (w),
7.44-6.97 (m)
7.45-6.78 (m)
8.40 (s)
2.34 (s)
4d
2930 (w), 2900 (w), 1605 (s),
1580 (s), 1500 (m), 1420 (s)
3400 (s), 3070 (w), 2980 (w),
2930 (w), 2800 (w), 1605 (s),
1590 (s), 1500 (s), 1440 (m),
1410 (s)
3300 (s), 3080 (w), 2950 (w),
2915 (w), 2880 (w), 1610 (s),
1450 (w), 1415 (s)
3200 (s), 3090 (w), 2820 (w),
1600 (s), 1580 (s), 1540 (s),
1480 (s), 1440 (s), 1410 (s)
3300 (s), 3070 (m), 3030 (m),
2900 (m), 2880 (m), 1610 (s),
1598 (m), 1550 (w), 1450 (s),
1420 (s)
8.40 (s)
—*
4е
7.80-6.28 (m)
7.44-6.98 (m)
7.30-6.94 (m)
8.30 (t, 3.89 (m);
3.69 (m)
4f
J = 1.2)
2.23 (s)
8.44 (s)
5b
5с
8.34 (t,
4.77 (d,
J = 1.2) J = 1.2)
3440 (m), 3080 (w),
2910 (w), 1600 (s), 1590 (s),
1550 (m), 1500 (s), 1450 (s),
1410 (m)
3410 (s), 3110 (w), 2910 (w),
1610 (s), 1540 (m), 1500 (m),
1370 (w), 1280 (s)
3400, 3210 (w), 3080 (w),
3000 (w), 2930 (s), 2900 (m),
2870 (m), 2750 (m), 1610 (s),
1540 (m), 1450 (s), 1410 (s)
3500 (w), 3110 (s), 3060 (s),
1600 (s), 1590 (s), 1540 (m),
1480 (m), 1450 (s), 1420 (s),
1400 (m)
7.42-6.94 (m)
8.42 (s)
2.33 (s)
5d
7.62-6.92 (m)
7.25-6.94 (m)
8.45 (s)
—*
5е
8.31 (t, 3.89 (m);
3.66 (m)
5f
J = 1.0)
2.36 (s)
7.38-6.96 (m)
8.42 (s)
5g
3420 (m), 3280 (m),
8.55 (s, 2Нtriazole); 8.63 (s)
5h
3115 (m), 1630 (m), 1620 (s),
7.48-7.07 (m)
1600 (m), 1510 (s), 1450 (s)
_______
* The signal of the OH group proton is in the region of the multiplet signals
of the aromatic and heterocyclic protons.
In the majority of cases the yield of azomethines 4 and 5 was 70-93%. Azomethine 4g was not obtained.
Even with a twofold excess of 2-chloroaniline 3g and maintaining at 40-50°C for 8 h unreacted aldehyde 1
remained in the reaction mixture (check by GLC). The analogous azomethine 5g was formed from 2,2'-bithienyl
in less than 45% yield. Azomethines 4f, 5f, and 5h were also formed in low yields. Aldehyde 1 did not react
with amine 3h under analogous conditions.
58

The synthesized azomethines 4 and 5 are solid substances, bright yellow to brown in color. The melting
points of compounds 4 were significantly lower than the melting points of the corresponding azomethines 5. A
similar regularity was also observed for unsubstituted 2,2'-dithienyl sulfide [5] and 2,2'-bithienyl [6] and also for
their 5-formyl derivatives. This may be caused by the more ordered structure of the molecules of 2,2'-bithienyl
derivatives compared with the structure of the analogous 2,2'-dithienyl sulfide derivatives, for which evidently
there is a larger number of conformers with different disposition of thiophene rings relative to one another.
Analysis of the spectral characteristics of compounds 4 and 5 (Table 2) enabled the assumption that
only one geometric isomer is formed for azomethines 4 and 5, analogous to the formation of only the anti form
of the Schiff's bases in the reaction of aromatic aldehydes with substituted anilines [7].
There was an intense absorption band at 1600-1620 cm-1 in the IR spectra of all the compounds
obtained. This band corresponds to the stretching vibrations of the azomethine group (C=N) [2]. Besides this
band the band for the stretching vibrations of associated hydroxyl group appears in the spectra of compounds 4f
and 5f at 3300 and 3400 cm-1 respectively. These data and also the data of 1H NMR spectra indicate the absence
of cyclization of azomethines into oxazolidines, which frequently accompanies the reaction of carbonyl
compounds with 2-aminoethanol (3f) [8]. The appropriate set of frequencies for the stretching vibrations of the
OH group was observed in the IR spectra at 3200-3400 cm-1, also the bands assigned to the stretching vibrations
of C–H at 2800-3100 cm-1, the C–H deformation vibrations at 800-1200 cm-1, and the stretching vibrations of
the C–S bond at 500-600 cm-1 were observed.
The protons of the aromatic and thiophene rings of azomethines 4 and 5 give a multiplet signal in the
1H NMR spectra of azomethines at 6.9-7.8 ppm. The signal of the azomethine proton is displayed at low field at
8.3-8.6 ppm under the anisotropic influence of the nitrogen atom. Its displacement towards low field is also
aided by such substituents at nitrogen atom in the aromatic ring as chlorine, bromine, methyl, and hydroxyl
groups (4d,e, 5b,d,e,g). 1,3,4-Triazole group on nitrogen atom displaces the signal of the azomethine proton
even more towards low field (5h), but benzyl substituent at the carbon atom of the azomethine bond displaces it
towards high field (4c, 5c).
So, six azomethine derivatives of 2,2'-dithienyl sulfide and five derivatives of 2,2'-bithienyl have been
synthesized and characterized for the first time. Due to the simple method of synthesizing 2,2'-dithienyl sulfide
developed in [9], its potentially biologically active azomethine derivatives become available substances like the
analogous compounds of the thiophene and bithienyl series. In addition these substances possess high synthetic
potential for obtaining new compounds with a broad spectrum of biological activity.
EXPERIMENTAL
1
The IR spectra were taken on a Specord IR-75 spectrometer in KBr disks. The H NMR spectra were
recorded on a Jeol FX 90 Q (90 MHz) instrument for 15-20% solutions of substances in CDCl3, internal
standard was HMDS. The completion of reaction was determined by the disappearance of the initial aldehyde
from the reaction mixture using a LKhM-80-1 gas-liquid chromatograph (column 3 × 2000 mm, liquid phase
silicone XE-60 (5%) on support Chromaton XE-60 N-AW HMDS, linear temperature programming at
12 deg/min).
Aldehydes 1 and 2 were obtained by the formylation of 2,2'-dithienyl sulfide and 2,2'-bithienyl by the
method of [10].
N-R-N-{(E)-[5-(2-Thienylthio)-2-thienyl]methylene}amines (4) and N-R-N-{(E)-[5-(2-Thienyl)-2-
thienyl]methylene}amines (5). The reaction of aldehydes 1 and 2 with amines 3 was carried out in a flask fitted
with a reflux condenser under stirring on a magnetic stirrer. Reactants were used in stoichiometric quantities.
After completion of the reaction (2-4 h) the reaction mixture was cooled. This caused crystallization of the
product, which was purified by recrystallization from ethanol. The synthetic conditions and characteristics of
the synthesized compounds are given in Table 1.
59

REFERENCES
1.
2.
P. I. Buchin and A. E. Lipkin, Derivatives of Thiophene and Bithienyl as Promising Antiseptics of a
New Group [in Russian], Izd. Sarat. Univ., Saratov (1974).
K. I. Vakhreeva, M. G. Viderker, P. I. Buchin, A. E. Lipkin, and T. B. Ryskina, Khim.-farm. Zh., No. 1,
24 (1972).
3.
4.
5.
V. S. Egorova, V. N. Ivanova, and H. I. Putokhin, Khim. Geterotsikl. Soedin., 829 (1967).
S. V. Kessar, P. S. Pahwa, Pawanjit, Paramjit Singh, and Y. P. Gupta, Indian J. Chem., 16B, 92 (1978).
M. G. Voronkov, E. N. Deryagina, L. K. Papernaya, E. N. Sukhomazova, N. A. Korchevin, and
G. G. Efremova, Khim. Geterotsikl. Soedin., 1614 (1986).
6.
M. G. Voronkov, E. N. Deryagina, E. N. Sukhomazova, O. I. Randin, V. V. Keiko, and I. D. Kalikhman,
Khim. Geterotsikl. Soedin., 1186 (1976).
7.
8.
9.
V. M. Potapov, Stereochemistry [in Russian], Khimiya, Moscow (1976).
E. D. Bergmann, Chem. Rev., 53, 309 (1953).
M. G. Voronkov, E. N. Deryagina, L. G. Klochkova, and A. S. Nakhmanovich, Zh. Org. Khim., 12, 1515
(1976).
10.
B. P. Fedorov and F. M. Stoyanovich, Zh. Obshch. Khim., 33, 2251 (1963).
60