Synthesis of novel star-shaped molecules based on a 1,3,5-triazine core linked to different heterocyclic systems as novel hybrid molecules

Article abstract of DOI:10.1039/d0ra09025e

The synthesis of novel star-shaped compounds based on an s-triazine core and linked to hexahydroacridinediones, pyrimido[4,5-b]quinolones, 1H-isoquinolino[2,1-a]quinolines, tetrahydro-4H-chromenes, dihydropyrano[2,3-c]pyrazoles, thiazole, or benzothiazole

Full text of DOI:10.1039/d0ra09025e

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Synthesis of novel star-shaped molecules based on
a 1,3,5-triazine core linked to different heterocyclic
systems as novel hybrid molecules†
Cite this: RSC Adv., 2020, 10, 44066
Hadeer M. Diab, Mostafa E. Salem, Ismail A. Abdelhamid
and Ahmed H. M. Elwahy
*
*
The synthesis of novel star-shaped compounds based on an s-triazine core and linked to
hexahydroacridinediones, pyrimido[4,5-b]quinolones, 1H-isoquinolino[2,1-a]quinolines, tetrahydro-4H-
chromenes, dihydropyrano[2,3-c]pyrazoles, thiazole, or benzothiazole as new hybrid molecules through
Michael and Hantzsch reactions is reported. For this purpose, 2,4,6-tris(4-formylphenoxy)benzaldehyde
was used as a versatile precursor.
Received 23rd October 2020
Accepted 2nd December 2020
DOI: 10.1039/d0ra09025e
rsc.li/rsc-advances
addition, the use of s-triazine derivatives as anticancer agents
has also been extensively reported. In this regard, 1,3,5-triazine
Introduction
Star-shaped molecules have attracted considerable attention in scaffold is present in some anticancer drugs, such as altret-
39–42
recent decades because of their large application as promising amine, trimelamol and irsogladine (Fig. 1).
compounds for use in optoelectronics and electrochromic
Furthermore, the development of hybrid molecules through
1–3
4–6
devices as well as in organic solar cells (OSCs). They are also the combination of different pharmacophores in one molecule
considered as building blocks for the creation of mesophases may improve their biological efficacy and overcoming drug
7
–9
43–45
with interesting mesomorphic and photophysical properties.
Applications of star-shaped molecules as building units for comprising 1,3,5-triazine and different heterocyclic systems were
resistance.
In this aspect, heterocyclic hybrid skeleton
10
33,46–49
dendrimers as well as in supramolecular host-guest chemistry found to exhibit modied therapeutic activities.
have also been reported. In this regard, we recently reviewed chemistry is a highly creative discipline due to its ability to create
Synthetic
11
12
the synthesis and application of star-shaped molecules.
new methodologies to contribute to the discovery of new drugs,
In particular, star-shaped molecules that contain 1,3,5- and to enable the synthesis of important molecules with novel
triazine as a central core have been found to play an important properties and functions in reasonable yields with a direct impact
13
role as powerful chelating agents and many of their derivatives on the welfare of the world. Motivated by these ndings and in
have been employed in combinatorial and supramolecular conjunction with our ongoing research work on poly(hetero-
14
50–67
chemistry. The planarity of 1,3,5-triazine moiety and its cycles) as well as the new concept in drug design,
we report
symmetric nature plays a key role in self-organizing ability herein on the synthesis of novel hybrid molecules containing
which enhances their use in the development of organic light- 1,3,5-triazine linked to different heterocyclic systems.
1
5,16
6,17,18
emitting diodes,
drimers,
liquid crystalline materials,
den-
19,20
21–23
and nonlinear optical materials.
In addition,
Results and discussion
some s-triazine derivatives were reported as corrosion inhibitors
24
for mild steel in 1 M HCl solution. Moreover, some s-triazine In general, the synthesis of star-shaped compounds bearing the
derivatives have recently found extensive use as reagents in the s-triazine core was achieved starting from 2,4,6-trichloro-1,3,5-
25
conversion of functional groups.
Moreover, s-triazine derivatives are an interesting class of
compounds due to their diverse pharmacological activities as
2
6–28
29
30,31
32,33
antibacterial,
antifungal, antiviral,
antimalarials,
34
35
antiprotozoals, anti-asthmatic activity, estrogen receptor
3
6
37,38
modulators,
cyclindependent kinase inhibitors.
In
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
E-mail: ismail_shafy@yahoo.com; aelwahy@hotmail.com
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/d0ra09025e
Fig. 1 Some anticancer drugs incorporating 1,3,5-triazine scaffold.
1
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Scheme 1 Synthesis of tris-aldehyde 3.
Scheme 2 Synthesis of tris(2,6-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrile) 5.
triazine due to the simple displacement of chlorine atoms by treatment of p-hydroxybenzaldehyde 2 with KOH in ethanol)
different nucleophiles. These reactions open access to many with one equivalent of 2,4,6-trichloro-1,3,5-triazine 1 in dime-
ꢀ
useful molecules of important applications in medicinal thylformamide at 0 C afforded 3 in 82% yield (Scheme 1).
1
2
chemistry as well as in material science. We utilized this
Firstly, we investigate the reactivity of tris(aldehyde) 3
0
00
strategy to synthesize 4,4 ,4 -((1,3,5-triazine-2,4,6-triyl)tris(oxy)) towards the synthesis of tris(2,6-dimethyl-1,4-dihydropyridine-
tribenzaldehyde (3), by a modied procedure to some re- 3,5-dicarbonitrile) 5 through reaction with 6 equivalents of 3-
68–70
ported methods,
as a precursor for a variety of star-shaped aminobut-2-enenitrile 4 in acetic acid under reux. Compound
compounds based on s-triazine. Thus, the reaction of three 5 was successfully obtained in 88% yield (Scheme 2).
equivalents of potassium 4-formylphenolate (obtained upon
Scheme 3 Synthesis of tris(hexahydroacridine-1,8-diones) 7.
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The structure of compound 5 was conrmed spectroscopi-
Besides, the three-component Hantzsch-like reaction of tris
1
cally, as the H NMR spectrum revealed a characteristic singlet (aldehyde) 3 with three equivalents of each of 6-aminouracil 8
integrated by 18H at d 2.06 for the six methyl groups. It also and 5,5-dimethyl-1,3-cyclohexanedione 6 in acetic acid at reux
showed a singlet signal at d 4.47 for the pyridine-H. In addition, in the presence of p-TSA as a catalyst yielded the corresponding
it exhibited a singlet signal characteristic for the NH group at tris(pyrimido[4,5-b]quinolines) 9 in 72% yield. In this case, the
1
3
d 9.58. Furthermore, the C NMR spectrum of 5 was found to be uncyclized adduct 10 has not been obtained (Scheme 4).
in agreement with the proposed structure, it showed the methyl
signal at d 18.3 and the pyridine-C at d 40.7.
Moreover, tris(hexahydroacridine-1,8-diones) 7 in which the appeared around 1668 cm . The H NMR spectrum of 9 sug-
acridinedione moiety is connected to 1,3,5-triazine core via gested the existence of a singlet signal at d 4.81 corresponding
ether linkage can also be obtained in good yield via multi- to H5. The NH group appeared as broad signals at d 8.59, 11.89,
component reaction of dimedone 6 with tris(aldehyde) 3 and and 12.01. All other signals appeared at their expected posi-
The IR spectrum of compound 9 suggested the presence of
ꢁ
1
NH groups at 3200 cm . In addition, the carbonyl groups
ꢁ
1
1
1
3
ammonium acetate in acetic acid at reux (Scheme 3).
tions. Moreover, the C NMR spectrum of 9 showed the C5 at
The IR spectra of compound 7 suggested the presence of NH d 40.2 and the carbonyl group at d 173 and 194.4.
ꢁ
1
group at 3277 cm . In addition, the carbonyl group appeared at
The synthesis of tris(1H-isoquinolino[2,1-a]quinoline-12-
712 cm . The H NMR spectrum of 7 suggested the existence carbonitrile) 12 was also studied by the reaction of tris-
of two singlets integrated by 36 protons at d 0.87 and d 1.01 aldehyde 3 with 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)
ꢁ
1
1
1
71
allocated to twelve CH groups. Moreover, the singlet signal at acetonitrile 11 and dimedone 6 in acetic acid at reux. The
3
d 4.70 is corresponding to H9. The NH group appeared as cyclocondensation reaction can also lead to the formation of
a broad singlet signal at d 9.20. All other signals appeared at tris(5H-isoquinolino[3,2-a]isoquinoline-13-carbonitrile)
13
1
3
their expected positions. Moreover, the C NMR spectrum of 7 (Scheme 5).
was found to be in accordance with the proposed structure, it The regioselectivity was approved on the basis of recent
showed the C9 at d 32.1 and the carbonyl group at d 194.8. All literature supporting the formation of 9,10-dimethoxy-13-(4-
other carbon signals appeared at their expected positions.
methoxyphenyl)-3,3-dimethyl-1-oxo-2,3,4,6,7,13-hexahydro-1H-
isoquinolino[2,1-a]quinoline-12-carbonitrile 14 (Fig. 2) using X-
Scheme 4 Synthesis of tris(pyrimido[4,5-b]quinolines) 9.
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Scheme 5 Synthesis of tris(1H-isoquinolino[2,1-a]quinoline-12-carbonitrile) 12.
NMR spectrum of compound 12 featured the pyridine-C13 at
37.7 ppm.
Our study was expanded to include the use of Michael
addition reactions as an effective method for the synthesis of
novel tris(2-amino-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile) 16. Thus, compound 16 was success-
fully obtained by a multicomponent reaction of one equivalent
of tris-aldehydes 3 with three equivalents of both malononitrile
15 and dimedone 6 in EtOH/piperidine (Scheme 6).
The constitution of compound 16 was spectroscopically
determined based on the basis of elemental analysis and
spectral data. The IR spectra of compound 16 indicated the
Fig. 2 Structure of hexahydro-1H-isoquinolino[2,1-a]quinoline-12-
carbonitrile 14.
ꢁ1
presence of amino group at 3365 and 3313 cm . In addition, it
ꢁ
1
revealed the cyano group at 2190 cm . The carbonyl group
ꢁ1
1
appeared as a broad band at 1684 cm . The H-NMR spectrum
of 16 suggested the existence of two singlets integrated by 18
protons at d 0.94 and d 1.04 assigned to six CH . In addition, it
3
ray crystallography and 2D-HMBC spectroscopy via the
Hantzsch-like reaction of 4-methoxybenzaldehyde with 2-(6,7-
dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile and dime-
revealed the pyran-H4 as a singlet signal at d 4.22 ppm.
Likewise, we have also successfully demonstrated the
synthesis of tris(6-amino-3-methyl-1,4-dihydropyrano[2,3-c]
pyrazole-5-carbonitrile) 19 and tris(benzene-4,1-diyl)tris(2-
amino-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile)
72
done in the presence of acetic acid.
The IR spectra of compound 12 indicated the presence of the
ꢁ1
cyano group at 2188 cm and the carbonyl group as a broad
ꢁ
1
1
band at 1629 cm . The H NMR spectra of 12 revealed a char-
20 in 73 and 82% yields by a three-component reaction of one
1
3
acteristic singlet signal at d 4.71 for H-13. In addition, the
C
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Scheme 6 Synthesis of tris(5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile) 16.
mole of tris-aldehyde 3 with three moles of both of malononi- the presence of the pyran-H4 and the pyrazole methyl protons as
trile 15 and pyrazolone 17 (in ethanol in the presence of cata- two singlet signals at d 4.64 and d 1.78, respectively.
lytic amount piperidine) or 4-hydroxycoumarin 18 (in the
presence of acetic acid/sodium acetate) (Scheme 7).
The infrared spectra of compound 20 indicated the presence
ꢁ
1
of amino group at n 3255 and 3184 cm . In addition, it revealed
ꢁ1
The structure of compound 19 was conrmed by their elemental the cyano band at n 2197 cm . The carbonyl group appeared as
ꢁ
1
1
analysis and spectral results. Thus, IR spectrum of compound 19 a broad band at n 1715 cm . The H NMR spectrum of 20
ꢁ
1
indicated the presence of amino group at n 3295 and 3168 cm
indicated the presence of the pyran-H4 as a singlet signal at
ꢁ
1
1
and a cyano group at n 2187 cm . The H NMR spectrum indicated d 4.49.
Scheme 7 Synthesis of tris(dihydropyrano[2,3-c]pyrazole-5-carbonitrile) 19 and tris(dihydropyrano[3,2-c]chromene-3-carbonitrile) 20.
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Scheme 8 Synthesis of tris(tetraketone) 21.
Scheme 9 Synthesis of tris(benzothiazole) 24 and tris(1H-phenanthro[9,10-d] imidazole) 25.
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The utility of tris-aldehyde 3 as a building block for novel a new building block for blue light-emitting materials (Scheme
74
tris(hexahydro-1H-xanthene-1,8(2H)-dione) 22 has also been 9).
attempted. Unfortunately, the reaction of one equivalent of 3
Compound 24 was conrmed by the absence of character-
with six equivalents of dimedone (6) in the presence of 15 mol% istic absorption bands or signals for CHO, NH or SH in its IR
2
,
1
of p-TSA in a mixture of ethanol/H
did not lead to the formation of 22 and instead the interesting dened on the basis of spectral data. Thus, its IR spectra indi-
tris(tetraketone) 21 was obtained in 83% yield (Scheme 8). cated the absence of a peak characteristic for a carbonyl group.
Tetraketone derivatives are considered not only as an In addition, it revealed the absorption of the NH group at
2
O (2 : 1) or DCE as solvents or H NMR spectra. The structure of the tris(imidazole) 26 was
ꢁ
1
1
important class of biologically active compounds but also as 3305 cm . The H NMR spectrum of 26 indicated the presence
signicant precursors for the synthesis of various fused of a singlet signal integrated by three protons at d 13.47
73
heterocyclic.
The structure of compound 21 was spectroscopically veried.
assigned to the NH protons.
The synthetic utility of tris-aldehyde 3 as building blocks for
In the IR spectrum, the carbonyl and the hydroxyl stretching novel tris(thiazoles) through Hantzsch thiazole synthesis was
ꢁ
1
frequencies were noticed at 1650 and 3345 cm , respectively. also investigated. Thus, the tris(aldehyde thiosemicarbazone)
1
The H NMR spectrum of 21 displayed a broad signal at d 9.20 28 was rst synthesized in 90% yield, by acid-catalyzed
75
characteristic for the OH protons in addition to the methine-H condensation of thiosemicarbazide 27 with tris(aldehyde) 3.
at d 4.42. Reaction of 28 with the corresponding N-(4-chlorophenyl)-2-
Subjecting the tris(aldehyde) 3 to the cyclocondensation oxopropanehydrazonoyl chloride 29 in reuxing ethanol/DMF
reaction with 2-aminothiophenol 23 in ethanol at reux in the in the presence of TEA as a catalyst gave the corresponding
presence of NaHSO afforded the tris(benzothiazole) 24 in 61% tris(arydiazenyl)thiazole 30 in 85% yield (Scheme 10).
3
yield (Scheme 9). Moreover, the three-component cyclo-
The structure of compound 30 has been veried by spectral
condensation reaction of tris-aldehyde 3 with 9,10-phenan- as well as elemental analyses. The IR spectra of 30 as a repre-
ꢁ1
threnequinone 25 and ammonium acetate afforded the sentative example showed an absorption band at 3424 cm due
1
corresponding tris(1H-phenanthro[9,10-d]imidazole) 26 as to the NH group. Moreover, its H NMR spectrum showed
Scheme 10 Synthesis of tris(arydiazenyl)thiazole 30.
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Scheme 11 Synthesis of 2,4,6-tris(4-arylthiazol-2 ylhydrazonomethylphenoxy)-1,3,5-triazines 33 and 34.
a D O-exchangeable signal at d 10.53 due to NH protons chlorophenyl)ethanone 32 in ethanol at reux in the presence
2
together with sharp singlet signals at d 2.56 and d 8.61 attrib- of few drops of TEA afforded 2,4,6-tris(4-(-(2-(4-arylthiazol-2-yl)
uted to the 4-CH
N]CH), respectively. All other protons appeared at the pre- and 81% yields, respectively (Scheme 11).
dicted chemical shis and integral values. In analogy, reaction of compound 28 with 2-bromo-1-(5-
3
of thiazole group and the methine protons hydrazono)methyl)phenoxy)-1,3,5-triazines 33 and 34 in 79
(
Furthermore, the reaction of 28 with three equivalents of methyl-1-phenyl-1H-pyrazol-4-yl)ethanone 35 in ethanol at
each of 2-bromo-1-phenylethanone 31 and 2-bromo-1-(4- reux in the presence of few drops of TEA afforded 2,4,6-tris(4-
Scheme 12 Synthesis of tris(thiazoles) 36, 38 and 40.
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-(2-(4-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazol-2yl)
Paper
(
interesting applications. Further analysis is underway to investi-
hydrazono)methyl)phenoxy)-1,3,5-triazine 36 in 66% yield gate the biological activities of the novel compounds. We believe
Scheme 12). Compound 35 was synthesized by the reaction of also that some of the new star-shaped molecules should exhibit
phenylhydrazine with ((dimethyl-amino) methylene)pentane- useful NLO properties on account of preliminary theoretical
,4-dione, obtained upon treatment of acetylacetone with calculation of their polarizability and hyperpolarizability parame-
dimethylformamide dimethylacetal (DMF/DMA), followed by ters. The theoretical as well as the experimental investigations are
(
2
52,76
bromination through treatment with Br
2
in AcOH.
still underway and will be published separately because of the large
In an attempt to construct novel tris(thiazole) linked to other quantity of data accumulated.
heterocylic moieties aiming at achieving the concept of molec-
ular hybridization, we studied the synthesis of novel 2,4,6-tris(4-
Experimental
General
(-(2-(4-(benzofuran-2-yl)thiazol-2-yl)hydrazono)-methyl) phenoxy)-
1,3,5-triazine 38 and 2,4,6-tris(4-(-(2-(4-(benzo[d]thiazol-2-yl)
thiazol-2-yl)hydrazono)methyl)phenoxy)-1,3,5-triazine 40 using Melting points were determined in open glass capillaries with
a similar strategy. Thus, reaction of tris(thiosemicarbazone) 28 a Gallenkamp apparatus. The infrared spectra were recorded in
with each of 1-(benzofuran-2-yl)-2-bromoethanone 37 and 1- potassium bromide disks on a Pye Unicam SP 3-300 and Shi-
(
benzo[d]thiazol-2-yl)-2-bromoethanone 39 in ethanol at reux in madzu FTIR 8101 PC infrared spectrophotometer. NMR spectra
the presence of TEA afforded 38 and 40 in 62 and 76% yields, were recorded with a Varian Mercury VXR-300 NMR spectrom-
respectively (Scheme 12).
eter operating at (300 MHz and 75 MHz) or Bruker AVS NMR
The structures of the newly synthesized compounds have spectrometer at (400 MHz and 101 MHz), respectively, using
been conrmed by spectral data as well as elementary analyses. TMS as an internal standard. Chemical shis were reported as
The IR spectrum of tris(pyrazole) 36 as a representative example d values in ppm. Mass spectra (EI) were obtained at 70 eV with
of this class of compounds showed an absorption band at a type Shimadzu GCMQP 1000 EX spectrometer. Analytical thin-
ꢁ
1
3427 cm
because of (NH) together with the absence of layer chromatography was performed using pre-coated silica gel
77
absorption band characteristic for C]S group. The symmetry 60 778 plates (Fluka), and the spots were visualized with UV
of compound 36 is represented by a characteristic set of signals light at 254 nm. Elemental analyses were performed on a Per-
1
within its H NMR spectrum. It revealed the presence of a D O- kin-Elmer 240 micoanalyser at the Micro analytical Center of
2
exchangeable singlet signal at d 12.18 attributable to NH Cairo University. All chemicals were purchased from Sigma-
protons, a singlet signal at d 6.84 attributed to C-5 protons of the Aldrich and used without further purication.
thiazole rings, and a singlet signal at d 8.03 because of methine
protons (N]CH). All other protons were observed at the pre-
dicted chemical shis and integral values.
0
00
Synthesis of 4,4 ,4 -((1,3,5-triazine-2,4,6-triyl)tris(oxy))
tribenzaldehyde (3)
A solution of p-hydroxybenzaldehyde (3 mmol) and KOH (3
mmol) in ethanol (10 ml) was stirred for 10 min at room
temperature. The solvent was then removed in vacuo and the
remaining potassium salt was collected, dissolved in DMF (5 ml),
Conclusions
The most popular strategy in drug design as well as in the
construction of important molecules is the synthesis of analogs of
existing active molecules. The aim of this work was to develop new
methodologies to tackle synthetic problems encountered in the
synthesis of star-shaped molecules that contain 1,3,5-triazine as
a central core with improved pharmacological and photophysical
properties. In this respect, a simple protocol for the preparation of
some star-shaped compounds based on s-triazine core linked to
hexahydroacridinediones, pyrimido[4,5-b]quinolones, 1H-iso-
quinolino[2,1-a] quinolines, tetrahydro-4H-chromenes, dihy-
dropyrano[2,3-c]pyrazoles, thiazole, or benzothiazole was
developed. Hantzch and Michael reactions have been used as
effective strategies for the synthesis of the target compounds from
easily accessible precursors under mild reaction conditions.
Moreover, multicomponent reactions (MCRs), which are associ-
ated with a range of advantages such as procedural efficiency,
shorter reaction times, energy savings, and lower costs and time-
consuming, were successfully used in this manuscript to synthe-
ꢀ
and stirred for 10 min at 0 C. A solution of the latter salt and
2
,4,6-trichloro-1,3,5-triazine (1 mmol) in DMF (5 ml) was allowed
ꢀ
to stir for 15 min at 0 C during which time KBr was precipitated.
The solvent was then removed in vacuo and the remaining
material was washed with water (20 ml), collected and crystallized
from H
mp 170–175 C. IR (KBr) n 2839, 2746, 1705 cm ; H NMR (300
MHz, DMSO-d ) d 7.46–7.49 (d, J 8.4 Hz, 6H, Ar–H), 7.95–7.98 (d, J
2
O/EtOH (3 : 1) to give 3 as a colorless powder; yield: 82%;
ꢀ
ꢁ1
1
6
1
3
8
.1 Hz, 6H, Ar–H), 9.98 (s, 3H, 3CHO). C NMR (100 MHz,
6
DMSO-d ) d 122.2, 131.1, 134.1, 155, 172.6, 191.8 ppm. MS (EI, 70
+
15 3 6
eV): m/z (%) 441 [M ]. Anal. calcd for C24H N O : C, 65.31; H,
3.43; N, 9.52. Found: C, 65.02; H, 3.29; N, 9.34.
0 00
,4 ,4 -(((1,3,5-Triazine-2,4,6-triyl)tris(oxy))tris(benzene-4,1-
4
diyl))tris(2,6-dimethyl-1,4-dihydropyridine-3,5-dicarbonitrile)
5)
(
size the target compounds. The combination of two fused To a warm solution of tris-aldehyde 3 (1 mmol) in glacial acetic
heterocyclic cores in a single molecular structure is supposed to acid (5 ml) was added 3-aminocrotononitrile 4 (6 mmol). The
take advantage of the pharmacological and physical properties of resulting solution was heated at reux for 1 h. The solid ob-
the resulting ligands. The successful synthesis of these compounds tained was collected and crystalized from DMF EtOH to give 5 as
ꢀ
should open an access to a variety of star shaped molecules with pale yellow crystals; yield: 88%; mp > 300 C. IR (KBr) n 3317
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ꢁ
1 1
(
NH), 2198 (CN) cm ; H NMR (400 MHz, DMSO-d
6
) d 02.06 (s, H13), 7.02 (s, 3H, Ar–H), 7.14–7.31 (m, 12H, Ar–H), 7.66 (s,
1
3
1
3
1
(
2
8H, 6CH ), 4.47 (s, 3H, 3CH), 7.29–7.36 (m, 12H, Ar–H), 9.58 (s, 3H, Ar–H). C NMR (100 MHz, DMSO-d ) d 28.2, 28.7, 28.8, 32.7,
3
6
1
3
H, 3NH). C NMR (100 MHz, DMSO-d ) d 18.3, 40.7, 82.9, 37.4, 43.6, 49.8, 56.1, 56.2, 84.9, 110.4, 110.9, 111.2, 114.3, 120.2,
19.8, 122.4, 129.2, 142.2, 147.5, 151.1, 173.5. MS (EI, 70 eV): m/z 122.1, 128.5, 131.3, 142.4, 147.2, 151.0, 152.3, 158.6, 172.5,
%) 828 [M ]. Anal. calcd for C48
0.28. Found: C, 69.27; H, 4.11; N, 20.02.
6
+
+
H
36
N
12
O
3
: C, 69.55; H, 4.38; N, 195.1. MS (EI, 70 eV): m/z (%) 1443 [M ]. Anal. calcd for
12: C, 72.33; H, 5.65; N, 8.73. Found: C, 72.07; H,
.49; N, 8.62.
87 81 9
C H N O
5
0 00
9
,9 ,9 -(((1,3,5-Triazine-2,4,6-triyl)tris(oxy))tris(benzene-4,1-
0
00
diyl))tris(3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-
,8(2H,5H)-dione) (7)
A mixture of tris-aldehyde 3 (1 mmol), dimedone 6 (6 mmol) and
4,4 ,4 -(((1,3,5-Triazine-2,4,6-triyl)tris(oxy))tris(benzene-4,1-
diyl))tris(2-amino-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile) (16)
1
ammonium acetate (5 mmol) in glacial acetic acid (3 ml) was To a mixture of tris-aldehyde 3 (1 mmol), malononitrile 15 (3
heated at reux for 6 h. The obtained crude solid was collected mmol) and dimedone 6 (3 mmol) in absolute ethanol (4 ml),
and crystalized from DMF/EtOH to give 7 as yellow crystals; piperidine (0.2 ml) was added. The reaction mixture was heated
ꢀ
yield: 83%; mp > 300 C. IR (KBr) n 3277 (NH), 1712 (C] at reux for 3 h. The crude solid formed was collected and
ꢁ
1 1
O) cm ; H NMR (400 MHz, DMSO-d
6
) d 0.87 (s, 18H, 6CH
3
), crystalized from DMF/EtOH to give 16 as buff powder; yield:
ꢀ
1
1
6
.01 (s, 18H, 6CH
2H, 6CH
.91–6.94 (d, J 8.4 Hz, 6H, Ar–H), 9.20 (s, 3H, 3NH). C NMR 3CH
) d 26.9, 29.6, 32.1, 32.6, 50.8, 112.3, 114.8, (m, 6H, 3CH
28.9, 138.4, 149.3, 155.5, 172.5, 194.8. MS (EI, 70 eV): m/z (%) (d, J 8.4 Hz, 6H, Ar–H), 7.17–7.19 (d, J 8.4 Hz, 6H, Ar–H).
3
), 2.00–2.18 (m, 12H, 6 CH
2
), 2.32–2.49 (m, 88%; mp 285–290 C. IR (KBr) n 3365, 3313 (NH
2
), 2190 (C^N),
) d 0.94 (s, 9H,
), 2.10–2.14 (m, 6H, 3CH ), 2.24–2.51
), 4.22 (s, 3H, 3CH), 7.02 (br, 6H, 3NH ), 7.11–7.13
ꢁ
1 1
2
), 4.70 (s, 3H, 3CH), 6.51–6.53 (d, J 8.4 Hz, 6H, Ar–H), 1684 (C]O) cm ; H NMR (400 MHz, DMSO-d
6
1
3
3
), 1.04 (s, 9H, 3CH
3
2
(
100 MHz, DMSO-d
6
2
2
1
3
1
1
C
+
170 [M ]. Anal. calcd for C H N O : C, 73.82; H, 6.71; N, 7.17. NMR (100 MHz, DMSO-d ) d 27.2, 28.9, 32.3, 35.5, 50.4, 58.6,
7
2
78
6
9
6
Found: C, 73.66; H, 6.49; N, 7.03.
113.2, 120.1, 122.0, 128.5, 142.3, 150.8, 159, 162.8, 165.9, 172.3,
+
196.1. MS (EI, 70 eV): m/z (%) 1005 [M ]. Anal. calcd for
0
00
5
,5 ,5 -(((1,3,5-Triazine-2,4,6-triyl)tris(oxy))tris(benzene-4,1-
C
57
H
51
N
9
O
9
: C, 68.05; H, 5.11; N, 12.53. Found: C, 67.76; H,
diyl))tris(8,8 dimethyl-2-thioxo-2,3,5,8,9,10-
5.03; N, 12.24.
hexahydropyrimido[4,5-b]quinoline-4,6(1H,7H)-dione) (9)
0
00
4
,4 ,4 -(((1,3,5-Triazine-2,4,6-triyl)tris(oxy))tris(benzene-4,1-
diyl))tris(6-amino-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-
-carbonitrile) (19)
crystalized from DMF to give 9 as creamy powder; yield: 72%; To a mixture of tris-aldehyde 3 (1 mmol), malononitrile 15 (3
A mixture of tris-aldehyde 3 (1 mmol), dimedone 6 (3 mmol) and
6-aminothiouracil 8 (3 mmol) in glacial acetic acid (3 ml) was
5
heated at reux for 3 h. The solid formed was collected and
ꢀ
ꢁ1
1
mp > 300 C. IR (KBr) n 3200 (NH), 1668 (C]O) cm ; H NMR mmol) and pyrazolone 17 (3 mmol) in absolute ethanol (4 ml),
(
300 MHz, DMSO-d ) d 0.92 (s, 9H, 3CH ), 1.01 (s, 9H, 3CH ), piperidine (0.2 ml) was added. The reaction mixture was heated
6 3 3
2
3
6
3
4
1
C
.06–2.22 (m, 6H, 3CH ), 2.45–2.48 (m, 6H, 3CH ), 4.81 (s, 3H, at reux for 3 h. The crude solid formed was collected and
CH), 7.05–7.08 (d, J 8.4 Hz, 6H, Ar–H), 7.22–7.25 (d, J 8.4 Hz, crystalized from EtOH to give 19 as creamy powder; yield: 73%;
2
2
ꢀ
H, Ar–H), 8.59 (br, 3H, 3NH), 11.89 (br, 3H, 3NH), 12.01 (br, mp 246–250 C; (EtOH). IR (KBr) n 3453 (NH), 3295, 3168 (NH
2
),
) d 1.78 (s, 9H,
2
), 7.12–7.15 (d, J
1
3
ꢁ1
1
H, 3NH). C NMR (75 MHz, DMSO-d
6
) d 26.9, 28.6, 32.3, 32.6, 2187 (C^N) cm ; H NMR (300 MHz, DMSO-d
), 4.64 (s, 3H, 3CH), 6.85 (s, 6H, 3NH
94.4. MS (EI, 70 eV): m/z (%) 1182 [M ]. Anal. calcd for 8.7 Hz, 6H, Ar–H), 7.19–7.21 (d, J 8.4 Hz, 6H, Ar–H), 12.08 (s, 3H,
6
0.2, 50.1, 94, 110.7, 120.8, 128.6, 143.6, 144.2, 149.5, 160.8, 173, 3CH
3
+
1
3
60
54 12 9 3 6
H N O S : C, 60.90; H, 4.60; N, 14.20. Found: C, 60.84; H, 3NH). C NMR (75 MHz, DMSO-d ) d 9.6, 35.6, 57.1, 97.6, 120.7,
4
.33; N, 14.03.
121.7, 128.4, 135.6, 141.5, 150.5, 154.7, 160.8, 172. MS (EI, 70
+
eV): m/z (%) 879 [M ]. Anal. calcd for C H N O : C, 61.43; H,
4
5
33 15 6
0
00
1
4
3,13 ,13 -(((1,3,5-Triazine-2,4,6-triyl)tris(oxy))tris(benzene-
,1-diyl))tris(9,10-dimethoxy-3,3-dimethyl-1-oxo-2,3,4,6,7,13-
3.78; N, 23.88. Found: C, 61.22; H, 3.59; N, 23.65.
0
00
hexahydro-1H-isoquinolino[2,1-a] quinoline-12-carbonitrile)
12)
A mixture of tris-aldehyde 3 (1 mmol), dimedone 6 (3 mmol) and
4,4 ,4 -(((1,3,5-Triazine-2,4,6-triyl)tris(oxy))tris(benzene-4,1-
diyl))tris(2-amino-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-
carbonitrile) (20)
(
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile 11 (3 A mixture of tris-aldehyde 3 (1 mmol), malononitrile 15 (3
mmol) in glacial acetic acid (3 ml) was heated at reux for 6 h. mmol), 4-hydroxycoumarin 18 (3 mmol) and sodium acetate (3
The formed crude solid was collected, washed with ethanol and mmol) in glacial acetic acid (3 ml) was heated at reux for 3 h.
crystalized from DMF to give 12 as yellow crystals; yield: 77%; The crude solid formed was collected and crystalized from
ꢀ
mp 260–262 C; (DMF). IR (KBr) n 2188 (C^N), 1629 (C] DMF/EtOH to give 20 as grey powder; yield: 82%; mp 255–
ꢁ
1
1
ꢀ
O) cm ; H NMR (400 MHz, DMSO-d ) d 0.99 (s, 9H, 3CH ), 1.02 265 C; (DMF/EtOH). IR (KBr) n 3323, 3184 (NH ), 2197 (C^N),
6
3
2
ꢁ1 1
(
(
(
s, 9H, 3CH ), 2.18 (m, 6H, 3CH ), 2.50 (m, 6H, 3CH ), 2.83–2.91 1715 (C]O) cm ; H NMR (400 MHz, DMSO-d ) d 4.49 (s, 3H,
m, 6H, CH
s, 9H, 3OCH
3
2
2
6
1
3
2
), 3.51–3.57 (m, 3H, CH
2
3 2
), 3.75 (s, 9H, 3OCH ), 3.82 3CH), 7.17–7.91 (m, 30H, Ar–H + 3NH ). C NMR (100 MHz,
3
), 3.89–3.92 (m, 3H, CH
2
), 4.71 (s, 3H, pyridine- DMSO-d
6
) d 36.8, 58.3, 104.2, 113.5, 117.1, 119.7, 122.1, 122.9,
RSC Adv., 2020, 10, 44066–44078 | 44075
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1
1
25.2, 129.3, 133.4, 141.5, 150.7, 152.7, 154, 158.5, 160.1, N-(4-chlorophenyl)-2-oxopropanehydrazonoyl chloride 29 was
73.5. MS (EI, 70 eV): m/z (%) 1071 [M ]. Anal. calcd for added. The reaction mixture was heated at reux for 6 h. The
+
C H N O : C, 67.23; H, 3.10; N, 11.76. Found: C, 66.94; H, formed solid was collected and crystalized from DMF to give 30
6
0
33 9 12
ꢀ
2
.88; N, 11.47.
as crimson red crystals; yield: 85%; decompose: 218–224 C;
(
ꢁ
1 1
DMF). IR (KBr) n 3424 (NH) cm ; H NMR (400 MHz, DMSO-
0
00 000 0000 00000
d ) d 2.56 (s, 9H, 3CH ), 7.28–7.35 (m, 18H, Ar–H), 7.84–7.86 (m,
2
,2 ,2 ,2 ,2 ,2 -((((1,3,5-Triazine-2,4,6-triyl)tris(oxy))
6
3
6
H, Ar–H), 8.62 (s, 3H, 3CH), 10.53 (s, 3H, 3NH). MS (EI, 70 eV):
tris(benzene-4,1-diyl)) tris (methanetriyl))hexakis(3-hydroxy-
,5-dimethylcyclohex-2-en-1-one) (21)
A mixture of tris-aldehyde 3 (1 mmol), dimedone 6 (6 mmol)
and p-TSA (15 mol%) in ethanol/H O (15 ml, 2 : 1) was heated
+
m/z (%) 1190 [M ]. Anal. calcd for C54
H, 3.47; N, 21.14. Found: C, 54.17; H, 3.23; N, 21.02.
41 13 18 3 3
H C N O S : C, 54.39;
5
2
at reux for 6 h. The solid formed was collected and crystalized
from EtOH to give 21 as colorless crystals; yield: 83%; mp 245–
General method for the synthesis of tris(thiazoles) 33, 34, 36,
8 and 40
3
ꢀ
ꢁ1
1
2
48 C; (EtOH). IR (KBr) n 3345 (OH), 1650 (C]O) cm ; H
To a solution of tris(aldehyde thiosemicarbazone) 28 (1 mmol)
in ethanol/DMF (20 ml, 3 : 1) containing TEA (0.1 ml, 1 mmol),
the appropriate 2-bromoethanones 31, 32, 35, 37 and 39 (3
mmol) were added. The reaction mixture was heated at reux
for 3 h. The formed crude solid was collected and crystalized
from the proper solvents to give 33, 34, 36, 38 and 40.
NMR (300 MHz, DMSO-d ) d 0.90 (s, 18H, 6CH ), 1.02 (s, 18H,
6
3
6
3
8
3
4
CH ), 2.04–2.27 (m, 12H, 6 CH ), 2.48–2.52 (m, 12H, 6CH ),
3 2 2
.33 (br, 3H, 3OH), 4.42 (s, 3H, methine-H), 6.56–6.59 (d, J
.7 Hz, 6H, Ar–H), 6.92–6.95 (d, J 8.7 Hz, 6H, Ar–H), 9.20 (br,
1
3
H, 3OH). C NMR (75 MHz, DMSO-d
6
) d 26.4, 28.7, 30.1, 31.8,
0.1, 50.1, 114.6, 114.8, 128.9, 134.8, 155.6, 162.5, 196.1. MS
+
(
81 3
EI, 70 eV): m/z (%)1227 [M ]. Anal. calcd for C72H N O15: C,
7
0.40; H, 6.65; N, 3.42. Found: C, 70.17; H, 6.38; N, 3.19.
2
,4,6-Tris(4-((2-(4-phenylthiazol-2-yl)hydrazineylidene)
methyl)phenoxy)-1,3,5-triazine (33)
Pale yellow powder; yield: 79%; mp 250–255 C; (DMF). IR (KBr)
2,4,6-Tris(4-(benzo[d]thiazol-2-yl)phenoxy)-1,3,5-triazine (24)
ꢀ
To a mixture of 2-aminothiophenol (3 mmol) 23, tris-aldehyde 3
ꢁ1 1
n 3434 (NH), 1564 (C]N) cm ; H NMR (300 MHz, DMSO-d )
d 7.20 (s, 3H, thiazole-H), 7.33–7.80 (m, 27H, Ar–H), 8.03 (s, 3H,
CH), 12.21 (br, 3H, 3NH). C NMR (75 MHz, DMSO-d
6
(
(
1 mmol) in absolute ethanol (10 ml), sodium hydrogen sulte
3 mmol) was added. The reaction mixture was heated at reux
1
3
6
) d 103.7,
for 4 h. The obtained solid was collected and crystalized from
acetic acid to give 24 as pale yellow powder; yield: 61%; mp 200–
2
d
1
1
21.8, 125.4, 127.2, 127.5, 128.5, 132.3, 134.6, 140.1, 151.8,
68.3, 172.9. MS (EI, 70 eV): m/z (%) 960 [M ]. Anal. calcd for
: C, 63.73; H, 3.78; N, 17.49. Found: C, 63.49; H,
+
ꢀ
ꢁ1
3
1
02 C. IR (KBr) n 1568 (C]N) cm ; H NMR (400 MHz, DMSO-
51 36 12 3 3
C H N O S
1
6 6
) d 7.42–8.13 (m, 24H, Ar–H). C NMR (100 MHz, DMSO-d )
3.47; N, 17.23.
d 121.5, 122.7, 123.1, 123.3, 126, 127.1, 129, 131.2, 135, 153.9,
+
1
66.6, 173.4. MS (EI, 70 eV): m/z (%) 756 [M ]. Anal. calcd for
: C, 66.65; H, 3.20; N, 11.10. Found: C, 66.33; H,
.03; N, 10.84.
42 24 6 3 3
C H N O S
3
2,4,6-Tris(4-((2-(4-(4-chlorophenyl)thiazol-2-yl)
hydrazineylidene)methyl) phenoxy)-1,3,5-triazine (34)
ꢀ
Pale yellow powder; yield: 81%; mp 265–267 C; (DMF). IR (KBr)
2
1
,4,6-Tris(4-(1H-phenanthro[9,10-d]imidazol-2-yl)phenoxy)-
,3,5-triazine (26)
ꢁ1 1
n 3432 (NH), 1566 (C]N) cm ; H NMR (300 MHz, DMSO-d
d 7.25 (s, 3H, thiazole-H), 7.32–7.35 (d, J 8.7 Hz, 6H, Ar–H), 7.42–
.39 (d, J 8.7 Hz, 6H, Ar–H), 7.68–7.71 (d, J 8.7 Hz, 6H, Ar–H),
.77–7.80 (d, J 8.7 Hz, 6H, Ar–H), 8.03 (s, 3H, CH), 12.21 (br, 3H,
NH). C NMR (75 MHz, DMSO-d ) d 104.4, 121.8, 127.1, 127.2,
6
28.5, 131.9, 132.3, 133.4, 140.2, 149.2, 151.8, 168.4, 172.9. MS
EI, 70 eV): m/z (%) 1062 [M ]. Anal. calcd for C51
C, 57.55; H, 3.13; N, 15.79. Found: C, 57.36; H, 3.01; N, 15.44.
6
)
To a solution of tris-aldehyde 3 (1 mmol) in absolute ethanol
10 ml), 9,10-phenanthrenequinone 25 (3 mmol) and ammo-
7
7
3
1
(
nium acetate (5 mmol) were added. The reaction mixture was
heated at reux for 3 h. The formed crude solid was collected
and crystalized from AcOH to give 26 as orange powder; yield:
8
13
+
(
3 12 3 3
H33Cl N O S :
ꢀ
1%; mp > 300 C; (AcOH). IR (KBr) n 3305 (NH), 1590 (C]
ꢁ
1 1
N) cm ; H NMR (400 MHz, DMSO-d
6
) d 7.48–8.88 (m, 36H,
Ar–H), 13.47 (s, 3H, 3NH). C NMR (100 MHz, DMSO-d
d 122.3, 122.9, 124.2, 124.9, 125.6, 125.8, 127.4, 127.9, 128.3,
1
3
6
)
2
,4,6-Tris(4-((2-(4-(3-methyl-1-phenyl-1H-pyrazol-4-yl)thiazol-
1
1
29.6, 129.8, 131.7, 135.7, 135.9, 137.5, 149.0, 153.1, 169.9,
72.6, 179.4. MS (EI, 70 eV): m/z (%)1005 [M ]. Anal. calcd for
2
-yl) hydrazineylidene)methyl)phenoxy)-1,3,5-triazine (36)
+
ꢀ
Pale yellow powder; yield: 66%; mp 245–250 C; (DMF). IR (KBr)
n 3427 (NH), 1565 (C]N) cm ; H NMR (300 MHz, DMSO-d
d 2.47 (s, 9H, 3CH ), 6.84 (s, 3H, thiazole-H) 7.31–7.90 (m, 30H,
Ar–H), 8.03 (s, 3H, CH), 12.18 (br, 3H, 3NH). C NMR (75 MHz,
C H N O : C, 78.79; H, 3.91; N, 12.53. Found: C, 78.46; H,
3
6
6
39
9
3
ꢁ1
1
6
)
.69; N, 12.32.
3
1
3
2
2
,4,6-Tris(4-((2-(5-((4-chlorophenyl)diazenyl)-4-methylthiazol-
-yl) hydrazineylidene)methyl)phenoxy)-1,3,5-triazine (30)
DMSO-d ) d 11.9, 101.8, 116.7, 121.8, 122.4, 124.9, 127.2, 127.7,
6
129.1, 132.4, 135.4, 138.7, 139.3, 168.1, 172.9. MS (EI, 70 eV): m/z
+
To a solution of tris(aldehyde thiosemicarbazone) 28 (1 mmol) (%) 1200 [M ]. Anal. calcd for C63
48 18 3 3
H N O S : C, 62.99; H,
in ethanol/DMF (20 ml, 3 : 1) containing TEA (0.1 ml, 1 mmol), 4.03; N, 20.99. Found: C, 62.71; H, 3.84; N, 20.68.
44076 | RSC Adv., 2020, 10, 44066–44078
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Paper
,4,6-Tris(4-((2-(4-(benzofuran-2-yl)thiazol-2-yl)
RSC Advances
2
15 L. Hu, J. Li, J. Huang and J. Yin, Chin. J. Chem., 2017, 35, 93–
hydrazineylidene)methyl) phenoxy)-1,3,5-triazine (38)
97.
ꢀ
16 M. Jung, K. H. Lee, J. Y. Lee and T. Kim, Mater. Horiz., 2020,
7, 559–565.
Brown powder; yield: 62%; mp 270–275 C; (DMF). IR (KBr) n
ꢁ1 1
3
423 (NH), 1563 (C]N) cm ; H NMR (300 MHz, DMSO-d
d 7.03 (s, 3H, thiazole-H), 7.24–7.73 (m, 27H, Ar–H), 8.05 (s, 3H,
CH), 12.26 (br, 3H, 3NH). MS (EI, 70 eV): m/z (%)1080 [M ].
Anal. calcd for C57 : C, 63.32; H, 3.36; N, 15.55.
Found: C, 63.11; H, 3.07; N, 15.23.
6
)
1
1
1
7 P. Bhagavath, R. Shetty and D. Sunil, Crit. Rev. Solid State
Mater. Sci., 2019, 45, 1–32.
8 K. C. Majumdar, N. De, B. Roy and A. Bhaumik, Liq. Cryst.,
+
3
36 12 6 3
H N O S
2010, 37, 1459–1464.
9 S. Matsumura, A. R. Hlil, C. Lepiller, J. Gaudet, D. Guay,
Z. Shi, S. Holdcro and A. S. Hay, J. Polym. Sci., Part A:
Polym. Chem., 2008, 46, 7207–7224.
2
,4,6-Tris(4-((2-(4-(benzo[d]thiazol-2-yl)thiazol-2-yl)
hydrazineylidene) methyl)phenoxy)-1,3,5-triazine (40)
2
2
2
2
2
0 K. K. Bansal, D. Kakde, U. Gupta and N. K. Jain, J. Nanosci.
Nanotechnol., 2010, 10, 8395–8404.
1 B. N. Veerabhadraswamy, H. K. Dambal, D. S. S. Rao and
C. V. Yelamaggad, ChemPhysChem, 2016, 17, 2225–2237.
ꢀ
Green crystals; yield: 76%; mp 265–270 C; (DMF). IR (KBr) n
ꢁ1 1
3
432 (NH), 1559 (C]N) cm ; H NMR (300 MHz, DMSO-d
6
)
d 7.32–8.05 (m, 27H, Ar–H), 8.05 (s, 3H, 3CH), 12.47 (s, 3H,
+
´
2 A. Laventure, G. De Grandpre, A. Soldera, O. Lebel and
C. Pellerin, Phys. Chem. Chem. Phys., 2016, 18, 1681–1692.
3 Y. Wang, T. Li, Y. Yin, Y. Jiang, G. Wang, D. Liu and J. Hua,
Optik, 2017, 142, 163–167.
3
NH). MS (EI, 70 eV): m/z (%)1131 [M ]. Anal. calcd for
C H N O S : C, 57.28; H, 2.94; N, 18.56. Found: C, 57.03; H,
5
4
33 15 3 6
2.77; N, 18.29.
4 A. El-Faham, K. A. Dahlous, Z. A. A. L. Othman, H. A. Al-
Lohedan and G. A. EL-Mahdy, Molecules, 2016, 21, 1–11.
5 G. Blotny, Tetrahedron, 2006, 62, 9507–9522.
Conflicts of interest
2
2
There are no conicts to declare.
6 Z. E. Koc, H. Bingol, A. O. Saf, E. Torlak and A. Coskun, J.
Hazard. Mater., 2010, 183, 251–255.
2
7 R. V. Patel, P. Kumari, D. P. Rajani and K. H. Chikhalia, Eur.
J. Med. Chem., 2011, 46, 4354–4365.
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