Metal-free multicomponent synthesis of novel macrocyclic tetrathiadienes with cyano and amino groups

Article abstract of DOI:10.1039/d1ra02616j

The first synthesis of 5,12-diamino-7,14-bis(aryl)-1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitriles was performed as a multicomponent macroheterocyclization of malononitrile, aryl aldehydes, and 1,2-ethanedithiol in the presence of a catal

Full text of DOI:10.1039/d1ra02616j

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Metal-free multicomponent synthesis of novel
macrocyclic tetrathiadienes with cyano and amino
groups†
Cite this: RSC Adv., 2021, 11, 18768
*
Nail S. Akhmadiev, Ekaterina S. Mescheryakova, Vnira R. Akhmetova
and Askhat G. Ibragimov
The first synthesis of 5,12-diamino-7,14-bis(aryl)-1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-
dicarbonitriles was performed as a multicomponent macroheterocyclization of malononitrile, aryl
aldehydes, and 1,2-ethanedithiol in the presence of a catalytic amount of triethylamine in ethanol. The
structures of the obtained macroheterocycles were confirmed by spectral methods, X-ray diffraction,
and MALDI TOF mass spectrometry.
Received 2nd April 2021
Accepted 17th May 2021
DOI: 10.1039/d1ra02616j
rsc.li/rsc-advances
formaldehyde, and a,u-dithiols.15 It is noteworthy that satu-
rated and unsaturated crown ethers of this type possess high
1 Introduction
complexing capacity towards so transition and alkali metals
and small organic molecules.16–20 Moreover, unsaturated thia-
crown ethers can be used for the creation of hybrid materials in
form 1 : 1 host–guest complexes with electron transfer to endo-
lanthanofullerene [La@C82-A(C2v)].21
Conformational features contribute to the unique nature of
thia macrocycles. For unsaturated thiacrown ethers oxidative
transformations and Z/E isomerization of double bonds upon
heating have been described.22 It was shown that tetrathiadiene
macrocyclic rings (–S–CH]CH–S–)2 preferably exist in a step-
ped conguration, forming close crystal packing (column
Organic suldes form an abundant cluster of biologically active
molecules, providing
a specic physiological effect. For
example, the methionine amino acid serves as a donor of
methyl groups in the body; allicin is formed upon mechanical
destruction of garlic cells and exhibits bactericidal properties;
biotin (vitamin) occurs as a part of enzymes and regulates the
protein and fat balance; umifenovir is an antiviral agent, and so
on.1–3 Unlike the traditional Ullmann and Chan Lam coupling
reactions, a simple strategy of a non-halide pathway to sulfur
compounds is the use of diaryl suldes as starting substrates.4–6
Another approach is based on the formation of a C–S bond by
transition metal-catalyzed thiomethylation via condensation of
thioacetals with CH-acids.7–9
Meanwhile, the growing demand for new materials, increasing
complexity of molecular drug targets, and chemotherapeutic drug
and antibiotic resistance account for the increasing relevance of
new thiamacrocyclic compounds.10,11 An example is provided by
the synthesis of a macroheterocyclic product containing a disulde
linker, octreotide, used for the treatment of tumors overexpressing
growth hormone (somatostatin).12
In this connection, a relevant task is to search for concep-
tually new approaches to the synthesis of sulfur-containing
macroheterocycles.13 One such approach does not require the
use of metal ions as template agents.14 Another original method
is multicomponent self-assembly of macroheterocyclic
compounds by (2 + 4 + 2)-cyclocondensation of amino alcohols,
Institute of Petrochemistry and Catalysis, Russian Academy of Science, 141 Prospekt
Octyabrya, 450075 Ufa, Russian Federation. E-mail: vnirara@mail.ru; Fax: +7 3472
842750; Tel: +7 3472 842750
† Electronic supplementary information (ESI) available. CCDC 2064003–2064005.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/d1ra02616j
Scheme 1 Evolution of the multicomponent reaction of malononitrile
with aldehydes and SH acids in the synthesis of six- to fourteen-
membered hetero(macro)cycles.
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Table
1 Dependence of product 4a yield from MCR condition
reagents in the presence of a basic catalyst gives pyridine skeleton I
or 6,7-dihydro-1,4-dithiepine structure II (Scheme 1).26,27
malononitrile 1 with 1,2-ethanedithiol 2 and 4-fluorobenzaldehyde 3aa
In this study, we demonstrated for the rst time a new
potential of malononitrile macroheterocyclization with
aromatic aldehydes and 1,2-ethanedithiol to give previously
No
Catalyst
Solvent
Product
Yield, %
1
2
3
4
5
6
7
8
Et3N
—
Et3N
Et3N
C2H5OH
C2H5OH
H2O
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
67
17
61
34
59
63
29
51
—
—
—
—
unknown
macroheterocyclic
5,12-diamino-7,14-bis(aryl)-
1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitriles
(Scheme 1).
CH2Cl2
Piperidine
C2H5OH
C2H5OH
C2H5OH
C2H5OH
C2H5OH
C2H5OH
C2H5OH
C2H5OH
DBUb
The base-catalyzed condensation of malononitrile with nucle-
ophilic reagents is, most oen, highly selective and gives hetero-
cyclic products in high yields.28 The model reaction involving
malononitrile, 1,2-ethanedithiol, and aryl aldehyde containing
electron-withdrawing uorine atom in the para-position was
utilized to study the effect of the catalyst type on the yield and
selectivity of the reaction. This reaction proceeded successfully
when the reactant molar ratio was 1 : 1 : 1, triethylamine (5 mol%)
was present as the catalyst, and the reaction mixture was heated to
70 ꢀC in ethanol or water. In this case, the target macrocycle was
formed in 67% or 61% yield (entries 1 and 3, Table 1).
Morpholine
K2CO3
L-Lysine$H2O
H3BO3
BF3$OEt2
NiCl2$6H2O
9
10
11
12
a
Reaction
conditions:
malononitrile
1
(2.5
mmol),
4-
uorobenzaldehyde 3a (2.5 mmol), 1,2-ethanedithiol 2 (2.5 mmol),
b
5 mol% of the catalyst, 8 mL of solvent, 70 ꢀC, stirring for 5 h. DBU
– diazabicycloundecene.
Ethanol was chosen as the solvent because malononitrile is
readily soluble in ethanol, while the resulting macrocycles are
poorly soluble (Scheme 2). The reaction was also efficiently
implemented with piperidine (59% yield of 4a) and DBU (63%,
entries 5 and 6, Table 1) used as organocatalysts. In the absence
of a catalyst, the yield of product 4a decreased to 17%. Product
4a was not formed when Lewis acids (H3BO3, BF3$OEt2, and
NiCl2$6H2O) were used as catalysts (5 mol%) (entries 10–12,
Table 1).
Fast addition of 1,2-ethanedithiol to the intermediate 5
resulted in complete gumming of the reaction mixture,
evidently due to the competing polymerization. A similar
outcome was obtained when long-chain a,u-dithiols (1,3-
propane-, 1,4-butanedithiols) were used as S-nucleophiles.
The use of 2-furaldehyde, formylferrocene, and acetaldehyde
under the developed conditions resulted in the formation of
powdered products insoluble in organic solvents such as CHCl3,
structures) provided by tight (zigzag-like) non-covalent contacts
between the sulfur atoms of the neighboring rings, which are
similar for hydrogen and p–p stacking bonds.23 These patterns
of intermolecular contacts determine the properties of con-
ducting materials and organic electrodes.24,25
The single examples of unsaturated S-containing macrohetero-
cycles and their high practical value stimulated us to design new
substituted 1,4,8,11-tetrathiacyclotetradeca-5,12-dienes. The intro-
duction of sulfur atoms with a lone pair of electrons into the mac-
rocycle and the presence of cyano and amino groups can endow
macromolecules with complexing and antioxidant properties.
2 Results and discussion
Previously, it was shown that a multicomponent condensation of
malononitrile with aldehydes and S-mono- or S,S-binucleophilic
Scheme 2 Model synthesis of amino- and cyano-substituted 1,4,8,11-tetrathiacyclotetradeca-5,12-diene 4a.
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Fig. 3 Fragment of molecule 4a with indicated long-range interac-
tions according to 1H–13C HMBC data (dC ppm).
Fig. 1 Molecular structure of the compound 5.
DMSO, or DMF, which precluded the spectroscopic character-
ization of the reaction mixture.
parameters are close to those described previously.29 The C^N
bond length is in line with established parameters,30 being
Another approach that can be successfully implemented is
the three-component reaction when reagents have added all at
once to the reaction mixture to give thiacrown ether 4a in 64%
yield (Scheme 2). Two-component procedure consisting in
preliminary mixing of malononitrile with aldehyde results in
the in situ intermediate formation of the Knoevenagel product,
2-(4-uorobenzylydene)malononitrile 5, within 40 min. More-
over, product 5 was isolated in a pure state in 95% yield and
described by X-ray and mass spectral method (Fig. 1). The use of
ready compound 5 as the reactant under similar conditions
gave macrocycle 4a in 44% yield (Scheme 2).
˚
1.1384(18) and 1.1380(16) A for the C6–N11 and C5–N8 bonds,
respectively. The molecule has a nearly planar geometry, the
root-mean-square deviation of atoms is 0.055 A.
˚
Thus, as shown in Scheme 2, three reactions follow the same
route: rst, the Knoevenagel product 5 is formed and then the
self-organization of dithiol molecules occurs by location
between two molecules of product 5 to realize the (2 + 2)-
cycloaddition. Considering the yield of product 4a, two macro-
heterocyclization reactions either with simultaneous mixing of
all three reactants or via in situ synthesis of intermediate 2-(4-
uorobenzylidene)malononitrile 5 are of preparative value.
The 1H NMR spectrum of macroheterocycle 4a exhibited
a triple set of high-eld signals at dH 2.74–2.84, 3.02–3.05 ppm, and
3.46–3.51 ppm with integrated intensity ratio of 1 : 1 : 2 (Fig. 2).
The crystals of 5 were obtained by slow evaporation of
a DMSO-d6 solution. The molecules of 5 crystallize in the
ꢀ
triclinic system with space group P1; the crystal lattice
Fig. 2 Splitting of proton signals of the ethylene group (SCH2CH2S)2 in the 1H NMR spectrum of macroheterocycle 4a in DMSO-d6 (400 MHz) at
room temperature (dH ppm).
Scheme 3 Catalytic macroheterocyclization of malononitrile with aryl aldehydes and 1,2-ethanedithiol.
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Table 2 Yields of compound 4a–i depending on the substituent (Ar) in the starting aldehydes
Compounds
Substituent Ar
Yield 4a, %
Compounds
Substituent Ar
Yield 4a, %
4a
4b
4c
4d
4e
4-F-C6H4
4-Cl-C6H4
3-F-C6H4
4-CF3-C6H4
4-(CH3O)–C6H4
67
61
58
68
59
4f
3,4-(CH3O)2–C6H3
4-CH3-C6H4
4-(CH3)2N–C6H4
1,3-Benzodioxol-5-yl
53
63
44
73
4g
4h
4i
a
The given yields for compounds 4a–i were obtained by method B.
According to HSQC 1H–13C NMR experiments, this group of Knoevenagel product 5 complicate the intramolecular nucleo-
signals was assigned to the ethylene protons (CH2(2,3,9,10)) philic addition of 1,2-dithiol giving 6,7-dihydro-1,4-
2
between sulfur atoms. Splitting of the geminal proton signals of dithiepines, but promote intermolecular (2 + 2) cycloaddition
the (SCH2CH2S)2 moieties was due to the magnetic non- of 2 to 5, resulting in the formation of macrocyclic tetrathia-
equivalence (anisochronous nuclei) of the hydrogen atoms on dienes with cyano and amino groups.
the NMR time scale and the lack of structural symmetry at the
sulfur atoms. It is noteworthy that hydrogen atoms of the CH2
groups in the SCH2CH2S chains are diastereotopic, obviously due
to the rigid conformation of the macroheterocycle 4a.31
As a result of the symmetry and conformational rigidity of
the macrocycles, the 13C NMR spectra exhibit a moderate
number of signals. The 13C NMR spectrum of compound 4a
shows two high-eld signals at dC 29.2 ppm (C(3)) and 31.5
(C(2)) ppm corresponding to the ethylene moiety between the
sulfur atoms. The characteristic signal of the methine carbon
atom occurs at dC 45.4 ppm. The signal at dC 85.6 ppm corre-
sponds to the quaternary carbon atom at the CN-substituted
double bond. The enamine carbon atom resonates in a low
eld at 163.0 ppm. The 13C NMR spectrum of compound 4a
shows splitting of the aromatic carbon signals, due to the
presence of uorine in the para-position of the ring, with spin–
spin coupling constants corresponding to published data: dC
161.8 (1JCF 242.8 Hz), 152.4, 136.0 (4JCF 2.4 Hz), 129.5 (3JCF 8.1
Hz), 120.3, and 115.9 (2JCF 21.4 Hz) ppm.32 The MALDI TOF
mass spectrum shows intense molecular ion peaks with m/z
555.0307 and 570.9909 corresponding to [M + Na]+ and [M + K]+
ions of the structure ascribed to macroheterocycle 4a.
The heteronuclear 1H–13C HMBC 2D NMR spectrum of
compound 4a showed a correlation between the C(2)H2 protons
and C(14) methine carbon atom; however, there were no clear-cut
cross-peaks with the C(5) quaternary carbon atom at the NH2
group, probably, due to slow conformational exchange (Fig. 3).
Under the developed conditions, the reaction was carried out
for the para- and meta-substituted aromatic aldehydes 3a–i with
electron-donating (CH3, OCH3, N(CH3)2) and withdrawing (F,
Cl, CF3) substituents (Scheme 3). The yields of the macro-
heterocycles 4a–i varied in the 44–73% range. The presence of
para-substituents in the aromatic ring of aldehydes was favor-
able for increasing the yield of the target macrocycles (Table 2).
With participation of para- and meta-substituted 1,3-
benzodioxol-5-ylmethanal (piperonal) the thiacrown ether 4i
was efficiently synthesized in 73% yield. However, there is
information in the literature that in the presence of ortho-
,ortho0-substituents in aromatic aldehydes, this reaction gave
Fig. 4 Molecular structure of unsaturated thiacrown ethers trans-4a
substituted 6,7-dihydro-1,4-dithiepines II.27 Obviously, the
and trans-4b. Non-hydrogen atoms are shown by thermal ellipsoids (p
meta- and/or para-substituents in the benzene ring in the ¼ 50%).
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Unsaturated thiacrown ethers 4a and 4b form crystal solvates plane. The obtained trans-thiacrown ether molecules have
(Fig. 5) in which the molecules of the major substance are a symmetry center, with the distances between the opposite
linked by N–H/O hydrogen bonds to DMSO molecules. Note sulfur atoms, S1–S10 and S2–S20, in 4a and 4b differing insig-
that the solvent molecules are disordered. 14-Membered cyclic nicantly (Fig. 4).
products trans-4a and trans-4b have E-geometry of the olenic
The molecules of compound 4a form crystals with a triclinic
˚
ꢀ
2
moieties. The C(sp )–S bond lengths are 1.771(2) and 1.752(6) A, crystal lattice (P1), while molecules of 4b crystallize in the
which agrees with the data for previously studied compounds.33 orthorhombic system (space group Pbca). In the crystals of 4a,
There exist endo- and exo-conformations of macrocyclic thio- thiacrown ether molecules form stacks along the a axis via
ethers, depending on whether the sulfur lone electron pairs C–H/N hydrogen bonds, whereas molecules of 4b are con-
point inside or outside the macrocyclic cavity, respectively. Like nected into chains along the b axis via DMSO molecules (Fig. 5).
other relatively simple thioethers,33 structures 4a and 4b have According to published data,34 molecules in the crystals of
the exo-conformation. The para-uoro- or para-chloroaryl unsaturated thiacrown ethers are linked by S/S contacts; the
moieties are arranged equatorially relative to the macrocycle distances between the sulfur atoms are equal to or are shorter
˚
than the sum of the van der Waals radii (S/S ¼ 3.7 A). In the
crystals of 4a and 4b, the distances between the sulfur atoms of
the tetrathiadiene rings are markedly longer than the sum of
the van der Waals radii of sulfur atoms (Fig. 5).
3 Conclusions
Thus, here we report the rst efficient method for constructing
macroheterocyclic structures from available reactants within
the framework of the metal-free concept. This method is based
on multicomponent macroheterocyclization of malononitrile,
meta- or para-substituted arylaldehydes, and 1,2-ethanedithiol
in the presence of triethylamine as a base catalyst. Due to the
presence of bifunctional groups in the reactants pseudo-six-
component cycloaddition occurs with the participation of SH-
groups of dithiol, C]C- and C^N-bonds of the Knoevenagel
adduct. The resulting 14-membered macroheterocycles repre-
sent a conceptually novel type of unsaturated systems contain-
ing cyano and amino groups. According to X-ray diffraction data
1,4,8,11-tetrathiacyclotetradeca-5,12-dienes have a E-geometry
of the olenic moieties and the exo-conformation of the
macrocyclic thioethers. Owingh to the presence of several
functional groups, these tetrathiamacrocycles (thiacrown
ethers) would be of interest for chemists specializing in the
coordination, supramolecular, and medicinal chemistry.
4 Experimental section
4.1. Materials and instruments
1
The reaction products were characterized by H and 13C NMR
spectra that were recorded on spectrometers Bruker Avance 400
NMR (400.13 MHz and 100.62 MHz) and Bruker Ascend III HD
500 (500.17 MHz and 125.78 MHz). Also 2D homo- (COSY) and
hetero- (HSQC, HMBC) nuclear spectra were obtained on
a Bruker Avance 500 in DMSO-d6 by Bruker standard proce-
dures, internal reference standard TMS. IR spectra were ob-
tained on a Bruker Vertex-70V FT-IR spectrometer for samples
prepared as a Nujol mull. UV spectra were recorded on a Perkin
Elmer Lambda 750 UV/VIS-spectrometer for DMSO solutions in
the wavelength range of 200–1000 nm using a 1 cm thick
cuvette. Matrix-assisted laser desorption/ionization (MALDI)
mass spectrum was recorded on a Bruker's device MALDI TOF
Fig. 5 Crystal packing of compounds 4a and 4b with indicated
Autoex III with sinapinic acid as a matrixes. GC-MS analysis of
compound was performed on Shimadzu GC 2010
intermolecular interactions (red dashed line) and S/S distances (black
dashed line).
5
a
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chromatograph equipped with a Shimadzu GCMS-QP2010 Ultra
mass selective detector and a Supelco 5 ms capillary column (60
m ꢁ 0.25 m ꢁ 0.25 mm), with helium as carrier gas. Elemental
analysis was performed on a Carlo Erba Model 1106 elemental
analyzer. Melting points were determined on a Koer hot-stage
microscope (RNMK 80/2617) apparatus. The reaction progress
was monitored by TLC method on Sorbl plates (PTSKh-AF-A),
eluent cyclohexane–CH2Cl2–EtOAc, 1 : 2 : 10, visualization
with iodine vapor.
4.1.4 5,12-Diamino-7,14-bis(3-uorophenyl)-1,4,8,11-
tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrile
(4c).
ꢀ
White powder, yield, 0.39 g (58%). Mp 192–194 C. Found: C,
54.18; H, 4.23; N, 10.63; S, 24.14. Anal. calc. for C24H22F2N4S4: C,
54.11; H, 4.16; N, 10.52; S, 24.08. IR (cmꢂ1): n ¼ 739, 763, 954,
1154, 1256, 1555, 1634, 2188, 3221, 3322, 3428. UV (nm): l ¼
283. 1H-NMR (ppm): d ¼ 7.45–7.39 (3H, m, Ar), 7.29 (4H, s, NH2),
7.22–7.14 (5H, m, Ar), 5.49 (2H, s, CH), 3.52–3.46 (2H, m, CH2),
3.07–3.02 (2H, m, CH2), 2.87–2.74 (4H, m, CH2). 13C-NMR
(ppm): d ¼ 162.4 (1JCF 242 Hz), 152.8, 142.4 (4JCF 6.8 Hz),
131.2 (2JCF 8.1 Hz), 123.8 (3JCF 3 Hz), 120.2, 115.0 (2JCF 21 Hz),
114.2 (2JCF 22.2 Hz), 84.9, 45.6, 31.5, 29.2. MS (MALDI TOF)
555.1459 [M + Na]+, 571.0966 [M + K]+.
4.1.1 Preparation of 5,12-diamino-7,14-bis(aryl)-1,4,8,11-
tetrasulfanylcyclotetradeca-5,12-diene-6,13-dicarbonitriles 4a–i
Method A. 4-Fluorobenzaldehyde (0.27 mL, 2.5 mmol) and
triethylamine (0.02 mL, 0.0125 mmol) are added to a solution of
malononitrile (0.17 g, 2.5 mmol) in ethanol (8 mL), and then 1,2-
ethanedithiol (0.21 mL, 2.5 mmol) is added dropwise under argon.
4.1.5 5,12-Diamino-7,14-bis[4-(triuoromethyl)phenyl]-
1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrile
(4d). White powder, yield, 0.54 g (68%). Mp 208–210 ꢀC. Found:
C, 49.42; H, 3.61; N, 8.79; S, 20.38. Anal. calc. for C26H22F6N4S4:
C, 49.35; H, 3.50; N, 8.85; S, 20.27. IR (cmꢂ1): n ¼ 692, 818, 1071,
1123, 1159, 1557, 1625, 2196, 3218, 3329, 3469. UV (nm): l ¼
284. 1H-NMR (ppm): d ¼ 7.76 (6H, d, J 8.4 Hz, Ar), 7.58 (2H, d, J
8 Hz, Ar), 7.35 (4H, s, NH2), 5.60 (2H, s, CH), 3.55–3.48 (2H, m,
CH2), 3.12–3.06 (2H, m, CH2), 2.90–2.77 (4H, m, CH2). 13C-NMR
(ppm): d ¼ 153.1, 144.3, 128.5 (2JCF 32 Hz), 128.4 (4JCF 1 Hz),
126.1 (3JCF 3.7 Hz), 124.6 (1JCF 271 Hz), 120.1, 84.7, 45.8, 31.4,
29.2. MS (MALDI TOF) 655.0454 [M + Na]+, 670.9974 [M + K]+.
4.1.6 5,12-Diamino-7,14-bis(4-methoxyphenyl)-1,4,8,11-
ꢀ
The reaction mixture is stirred at 70 C for 4 h, ltered, washed
with ethanol (2 ꢁ 10 mL), and dried in air to give 5,12-diamino-
7,14-bis(4-uorophenyl)-1,4,8,11-tetrasulfanylcyclotetradeca-5,12-
diene-6,13-dicarbonitrile 4a in 67% yield.
Method B. A mixture of malononitrile (0.17 g, 2.5 mmol), 4-
uorobenzaldehyde (0.27 mL, 2.5 mmol) and triethylamine
(0.02 mL, 0.0125 mmol) in 8 mL of ethanol was stirred under
argon at room temperature for 40 min. Then 1,2-ethanedithiol
(0.21 mL 2.5 mmol) is added dropwise. The reaction mixture is
ꢀ
stirred at 70 C for 4 h, ltered, washed with ethanol (2 ꢁ 10
mL), and dried in air to give macroheterocycle 4a is obtained
with a yield of 64%.
tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrile
(4e).
ꢀ
Method C. To a suspension of 2-(4-uorobenzylidene)malo-
nonitrile (0.43 g, 2.5 mmol) in 8 mL of ethanol, 1,2-ethanedi-
thiol (0.21 mL, 2.5 mmol) is added dropwise in an argon
atmosphere. The reaction mixture is stirred at 70 ꢀC for 4 h,
ltered, washed with ethanol (2 ꢁ 10 mL) and dried in air to
give macroheterocycle 4a is obtained with a yield of 44%.
4.1.2 5,12-Diamino-7,14-bis(4-uorophenyl)-1,4,8,11-
White powder, yield, 0.41 g (59%). Mp 164–166 C. Found: C,
56.02; H, 5.14; N, 10.11; S, 22.09. Anal. calc. for C26H28N4O2S4: C,
56.09; H, 5.07; N, 10.06; S, 20.04. IR (cmꢂ1): n ¼ 820, 1032, 1179,
1259, 1511, 1554, 1631, 2192, 3218, 3322, 3425. UV (nm): l ¼
1
286. H-NMR (ppm): d ¼ 7.30 (4H, d, J 8.4 Hz, Ar), 7.16 (4H, s,
NH2), 6.91 (4H, d, J 8 Hz, Ar), 5.41 (2H, s, CH), 3.50–3.45 (2H, m,
CH2), 3.33 (6H, s, CH3), 3.05–3.00 (2H, m, CH2), 2.82–2.72 (4H,
m, CH2). 13C-NMR (ppm): d ¼ 159.0, 151.9, 131.8, 128.7, 120.4,
114.3, 86.3 (C-6,13), 55.6 (C-34,36), 45.6 (C-7,14), 31.5, 29.2. MS
(MALDI TOF) 579.0371. [M + Na]+, 595.0151 [M + K]+.
4.1.7 5,12-Diamino-7,14-bis(3,4-dimethoxyphenyl)-
tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrile
(4a).
ꢀ
White powder, yield, 0.45 g (67%). Mp 194–198 C. Found: C,
54.23; H, 4.25; N, 10.47; S, 24.22. Anal. calc. for C24H22F2N4S4: C,
54.11; H, 4.16; N, 10.52; S, 24.08. IR (cmꢂ1): n ¼ 721, 772, 826,
1092, 1239, 1604, 1632, 2191, 3219, 3324, 3432. UV (nm): l ¼
279. 1H-NMR (ppm): d ¼ 7.42–7.39 (4H, m, Ar), 7.24 (4H, s, NH2),
7.21–7.18 (4H, m, Ar), 5.47 (2H, s, CH), 3.51–3.46 (2H, m, CH2),
3.06–3.02 (2H, m, CH2), 2.84–2.74 (4H, m, CH2). 13C-NMR
(ppm): d ¼ 161.8 (1JCF 242.8 Hz), 152.4, 136.1 (4JCF 2.4 Hz),
129.5 (3JCF 8.1 Hz), 120.3, 115.9 (2JCF 21.4 Hz), 85.5, 45.4, 31.5,
29.2. MS (MALDI TOF): 555.0307 [M + Na]+, 570.9909 [M + K]+.
4.1.3 5,12-Diamino-7,14-bis(4-chlorophenyl)-1,4,8,11-
1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrile
(4f). White powder, yield, 0.41 g (53%). Mp 122–124 ꢀC. Found:
C, 54.61; H, 5.17; N, 9.12; S, 20.86. Anal. calc. for C28H32N4O4S4:
C, 54.52; H, 5.23; N, 9.08; S, 20.79. IR (cmꢂ1): n ¼ 740, 774, 1024,
1141, 1263, 1559, 1640, 2194, 3218, 3317, 3384. UV (nm): l ¼
285. 1H-NMR (ppm): d ¼ 7.16 (4H, s, NH2), 7.00–6.91 (6H, m, Ar),
5.38 (2H, s, CH), 3.49–3.45 (2H, m, CH2), 3.36 (12H, s, CH3),
3.04–3.00 (2H, m, CH2), 2.81–2.73 (2H, m, CH2). 13C-NMR
(ppm): d ¼ 151.9, 148.9, 148.7, 132.1, 120.6 (C-16,25), 119.8,
112.2, 111.4, 86.1 (6,13), 56.0 (C-38,34), 55.9 (C-40,36), 45.9,
31.5, 29.2. MS (MALDI TOF) 639.1999 [M + Na]+, 655.1392 [M +
K]+.
tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrile
(4b).
ꢀ
White powder, yield, 0.43 g (61%). Mp 192–194 C. Found: C,
51.07; H, 3.85; N, 9.87; S, 22.74. Anal. calc. for C24H22Cl2N4S4: C,
50.96; H, 3.92; N, 9.91; S, 22.68. IR (cmꢂ1): n ¼ 723, 817, 1014,
1114, 1207, 1308, 1556, 1630, 2193, 3220, 3329, 3435. UV (nm): l
¼ 289. 1H-NMR (ppm): d ¼ 7.43 (4H, d, J 8 Hz, Ar), 7.38 (4H, d, J
8 Hz, Ar), 7.27 (4H, s, NH2), 5.48 (2H, s, CH), 3.51–3.46 (2H, m,
CH2), 3.07–3.03 (2H, m, CH2), 2.85–2.74 (4H, m, CH2). 13C-NMR
(ppm): d ¼ 152.7, 138.7, 132.6, 129.4, 129.2, 129.1, 120.2, 85.2
(C-6,13), 45.5 (C-7,14), 31.5, 29.2. MS (MALDI TOF): 587.1102 [M
+ Na]+, 603.0500 [M + K]+
4.1.8 5,12-Diamino-7,14-bis(4-methylphenyl)-1,4,8,11-
tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrile
(4g).
ꢀ
White powder, yield, 0.41 g (63%). Mp 192–194 C. Found: C,
59.63; H, 5.31; N, 10.74; S, 24.39. Anal. calc. for C26H28N4S4: C,
59.51; H, 5.38; N, 10.68; S, 24.43. IR (cmꢂ1): n ¼ 723, 816, 1019,
1113, 1263, 1609, 2183, 3198, 3311, 3435. UV (nm): l ¼ 290. 1H-
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NMR (ppm): d ¼ 7.26 (4H, d, J 8 Hz, Ar), 7.18 (4H, s, NH2), 7.15
(4H, d, J 8 Hz, Ar), 5.42 (2H, s, CH), 3.50–3.45 (2H, m, CH2), 3.05–
3.01 (2H, m, CH2), 2.81–2.73 (4H, m, CH2), 2.28 (6H, s, CH3). 13C-
NMR (ppm): d ¼ 152.0, 137.2, 136.8, 129.5, 127.4, 120.3 (C-
16,25), 86.1 (C-6,13), 45.9, 31.4, 29.2, 21.1 (C-33,34). MS
(MALDI TOF) 547.0865, [M + Na]+, 563.0848 [M + K]+.
Conflicts of interest
There are no conicts of interest to declare.
Acknowledgements
4.1.9 5,12-Diamino-7,14-bis[4-(dimethylamino)phenyl]-
1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrilꢀe
(4h). Light brown powder, yield, 0.32 g (44%). Mp 152–154 C.
Found: C, 57.74; H, 5.81; N, 14.51; S, 22.06. Anal. calc. for
This work was nancially partly supported by the Russian
Science Foundation (project no. 19-73-00070). The structural
data were obtained with the nancial support of the Russian
Ministry of Education and Science (project no. 2019-05-595-000-
058) on unique equipment at the “Agidel” Collective Usage
Center (Ufa Federal Research Center, Russian Academy of
Sciences) and within the framework of the State Assignment
AAAA-A19-119022290010-9.
C
28H34N6S4: C, 57.70; H, 5.88; N, 14.42; S, 22.01. IR (cmꢂ1): n ¼
802, 952, 1020, 1232, 1529, 1554, 1632, 2190, 3214, 3311, 3416.
UV (nm): l ¼ 279. 1H-NMR (ppm): d ¼ 7.19 (4H, d, J 8.4 Hz, Ar),
7.08 (4H, s, NH2), 6.67 (4H, d, J 8 Hz, Ar), 5.33 (2H, s, CH), 3.48–
3.43 (2H, m, CH2), 3.03–2.98 (2H, m, CH2), 2.87 (12H, s, CH3),
2.79–2.70 (4H, m, CH2). 13C-NMR (ppm): d ¼ 151.4, 150.2, 128.2,
127.1, 120.6, 112.6, 86.8 (C-6,13), 45.8 (C-7,14), 40.6, 31.5, 29.2.
MS (MALDI TOF) 581.1190. [M + H]+, 603.1167 [M + Na]+.
4.1.10 5,12-Diamino-7,14-bis(1,3-benzodioxol-5-yl)-
1,4,8,11-tetrathiacyclotetradeca-5,12-diene-6,13-dicarbonitrile
(4i). White powder, yield, 0.52 g (73%). Mp 186–188 ꢀC. Found:
C, 53.49; H, 4.21; N, 9.52; S, 22.04. Anal. calc. for C26H24N4O4S4:
C, 53.40; H, 4.14; N, 9.58; S, 21.93. IR (cmꢂ1): n ¼ 785, 928, 1039,
1252, 1326, 1554, 1633, 2195, 3219, 3316, 3416. UV (nm): l ¼
284. 1H-NMR (ppm): d ¼ 7.17 (4H, s, NH2), 6.86–6.94 (6H, m, Ar),
6.01 (4H, s, OCH2O), 5.37 (2H, s, CH), 3.49–3.43 (2H, m, CH2),
3.03–2.98 (2H, m, CH2), 2.79–2.71 (4H, m, CH2). 13C-NMR
(ppm): d ¼ 152.1, 147.7, 147.1, 133.6, 120.9, 120.4, 108.7,
107.8, 101.6, 86.1 (C-6,13), 45.8 (C-7,14), 31.6, 29.3. MS (MALDI
TOF) 607.1328. [M + Na]+, 623.0609 [M + K]+.
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