Sustainable Catalytic Process with a High Eco-scale Score for the Synthesis of Novel Series of Bischalcones through Claisen–Schmidt Condensation

Article abstract of DOI:10.1002/jhet.3063

An efficient, sustainable, and green method for the synthesis of novel series of bischalcones was developed using an environmentally benign ionic liquid as catalyst under ultrasound irradiation. This new catalyst affords diverse bis-α, β-unsaturated keton

Full text of DOI:10.1002/jhet.3063

Month 2017
Sustainable Catalytic Process with a High Eco-scale Score for the
Synthesis of Novel Series of Bischalcones through
Claisen–Schmidt Condensation
Wael A. A. Arafaa,b
*
aChemistry Department, College of Science, Aljouf University, P.O. Box 72341, Sakaka, Aljouf,
Kingdom of Saudi Arabia
bChemistry Department, Faculty of Science, Fayoum University, P.O. Box 63514, Fayoum City, Egypt
*
E-mail: waa00@fayoum.edu.eg; waarafa@ju.edu.sa
Received September 17, 2017
DOI 10.1002/jhet.3063
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
An efficient, sustainable, and green method for the synthesis of novel series of bischalcones was devel-
oped using an environmentally benign ionic liquid as catalyst under ultrasound irradiation. This new catalyst
affords diverse bis-α, β-unsaturated ketones in excellent yields under ambient reaction conditions in water.
Moreover, the catalyst found to be active down to 15 mol% and affords the products with up to 96% yield.
The process is eco-sustainable since this ionic liquid is ease of recovery and reuse for at least five successive
cycles without diminishing of the yield and catalyst leaching. Other merits of this protocol comprise its
operational simplicity, short reaction time, non-chromatographic purification procedure, and wide functional
groups tolerance. Furthermore, this catalytic system is applicable for the gram-scale preparation of
bischalcones, scoring well in a number of green metrics.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
reactions as well [4]. A great number of anions and
cations permit many chemical and physical properties to
be accomplished, and thus, the concepts “task-specific”
and “designer” ILs have been developed [5]. Claisen–
Schmidt condensation is considered as one of the most
important reactions in organic synthesis for C–C bond
construction. It has been utilized for the preparation of
biologically active chalcones, significant chemical
intermediates, polymers, and precursors of isoflavonoids
and flavonoids [6]. The most conventional strategies for
the synthesis of chalcones could be acquired through
Claisen–Schmidt condensation achieved in either basic or
acidic media under homogeneous conditions followed by
in situ dehydration [7]. As a potential substitutional,
heterogeneous catalysts have as well been utilized for
Claisen–Schmidt condensation, such as Brønsted acids,
Lewis acids, solid acids, and solid bases [8].
As of late, the increasing concern in the development of
environmentally friendly reactions has laid robust
foundations for the connotations of “green chemistry”
and “atom economy.” In the view of these concepts,
water appears to be an inexhaustible, non-flammable,
innocuous, and abundantly available solvent [1]. Because
of these unique properties and their versatile, the
designing of synthetically applicable aqueous reactions
has received much attention [2]. Recently, ionic liquids
(ILs) have gained considerable interest as potentially
green media for an extensive variety of applications in
chemistry, materials sciences, and electrochemistry [3]. In
spite of the fact that the ILs were at first presented as an
alternative green reactions media, nowadays, they are
showing substantial roles in catalyzing a variety of
© 2017 Wiley Periodicals, Inc.

W. A. A. Arafa
Vol 000
Notwithstanding, the waste disposal troubles and tedious
RESULTS AND DISCUSSION
recovery processes of these catalysts from the reaction
medium still environmental impediment upon their
employment on an industrial scale. Recently, some IL
catalysts have been endeavored in Claisen–Schmidt
Initially, we commence our investigation with the
optimization of the Claisen–Schmidt condensation using
6-fluorochroman-4-one
1b
(1
mmol)
and
condensation, and they demonstrate
a
valuable
terephthalaldehyde 2d (0.5 mmol) as model substrates
(Table 1). Our initial endeavor employing conventional
stirring conditions in ethanolic sodium hydroxide solution
at room temperature afforded the hitherto unreported
3,30-(1,4-phenylenebis(methanylylidene))bis(chroman-4-
one) 3h in mere yield (37%) with the many reactants
remaining unreacted even running the reaction for long
time (Table 1, entry 1). Next, on performance the same
reaction under ultrasound irradiation (40 kHz) yielded
43% of the product (3h) (Table 1, entry 2). Upon
examining the role of solvents other than ethanol viz.
methanol, dioxane, and dimethylformamide (DMF), we
noticed that none could furnish satisfactory yield of the
required product (Table 1, entries 4–5). Switching to
water afforded the product 3h in superior yields (64%,
Table 1, entry 6). Anticipating furthermore enhancement
in the reaction yield, a series of base catalysts such as
LiOH, piperidine (Pip), triethylamine (TEA), and 1,4-
improvement in the chalcones yield [9]. Nevertheless,
most of them are difficult to recover, poisonous, and
consumed long reaction time; in addition, the products, in
some cases, must be extracted with organic solvents [10].
Moreover, ultrasound-assisted synthesis has received
great interest in recent years in promoting efficacy, saving
energy, and diminishing reaction times in the synthesis of
several classes of organic compounds [11]. However, to
our knowledge, the combined use of ultrasound
technology and ILs in water as green solvent to achieve
the preparation of chalcones has not been reported as yet.
In pursuit of development a sustainable Claisen–Schmidt-
type reaction, herein, an eco-friendly green protocol for
the synthesis of new series of chalcone derivatives under
ultrasound-assisted conditions in water using novel IL,
[DABCO-EtOH][AcO], as recyclability catalyst was
reported.
Table 1
Optimization of the reaction conditions for the synthesis of (3E,30E)-3,30-(1,4-phenylenebis(methanylylidene))bis(6-fluorochroman-4-one) 3h.
Entry
Solvent
Catalyst
Method
Time
Yield
1
2
3
4
5
6
7
8
9
10
EtOH
EtOH
MeOH
Dioxane
DMF
H2O
H2O
H2O
H2O
H2O
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
LiOH
Pip
Stirring
US
US
US
US
US
US
US
US
12 h
37
43
40
33
37
64
45
28
36
55
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
TEA
DABCO
US
Scheme 1. Synthesis of the [DABCO-EtOH]AcO] and [DABCO-H]AcO] ionic liquids.
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Sustainable Catalytic Process with a High Eco-scale Score for the Synthesis of
Novel Series of Bischalcones through Claisen–Schmidt Condensation
diazobicyclo[2.2.2]octane (DABCO) were screened (Table 1
, entries 7–10). Unexpectedly, all the aforementioned
catalytic systems provided no better results, with the
exception of DABCO, providing the maximum yield
(55%). These results prompted us to study the
aforementioned reaction under other catalytic systems.
Table 2
Optimization of the reaction conditions for the synthesis of (3E,30E)-3,30-(1,4-phenylenebis(methanylylidene))bis(6-fluorochroman-4-one) 3h in water.
Entry
Catalyst (mol%)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
10
15
7
5
1
20
25
15
10
10
15
20
30
10
10
10
93
95
91
88
72
95
94
63a
aUsing [DABCO-H][OAc] (C) as catalyst.
Scheme 2. Synthesis of bischalcone derivatives 3a–l by using [DABCO-EtOH][OAc].
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Owing to the usage of ILs increased the reaction yields
of Claisen–Schmidt condensation reactions and the
reasonable yield obtained on using DABCO in the
aforementioned model reaction, both these observations
led us to restrict our investigation to the design of novel
IL based on DABCO. The new DABCO-based IL,
[DABCO-EtOH][AcO] (B) was prepared from
commercially available 2-chloro-1-ethanol and DABCO
followed by refluxing with sodium acetate as an ion
exchange reagent (Scheme 1).
In order to investigate the dual catalytic roles of the
novel IL (B), the condensation of 6-fluorochroman-4-one
1b (1 mmol) and terephthalaldehyde 2d (0.5 mmol) in
water under ultrasound irradiation was selected as model
reaction, and the results are summed up in Table 2. On
using 10 mol% of [DABCO-EtOH][AcO] (B), the
reaction proceeded efficiently and afforded the required
product in excellent yield (93%) within 10 min (Table 2,
entry 1). In order to study the effect of catalyst loading
on Claisen–Schmidt condensation, various amounts of
catalyst were used on the model reaction. It was found
that 15 mol% of the IL catalyst afforded the highest yield
(95%) of the desired product 3h in 10 minutes (Table 2,
entry 2). When the catalyst amount was diminished to 7
and 5 mol%, the product yield was still acceptable, while
the reaction time was increased to 15 and 20 min,
respectively (Table 2, entries and 4). Further
3
diminishing the catalytic amount of IL to 1 mol%,
moderate yield (72%) was obtained even after long
reaction time (Table 2, entry 5). Moreover, the reaction
yield not enhanced by increasing the amount of IL
catalyst over 20 mol% (Table 2, entries 6 and 7),
establishing 15% mol of IL as optimal for this reaction.
Therefore, ultrasound irradiation of 1b (1 mmol), 2d
(0.5 mmol) using 15 mol% of [DABCO-EtOH][AcO] (B)
at room temperature for 10 min in water was established
as the optimum conditions affording bischalcone (3h) in
95% yield (Table 2, entry 2). The scope and generality of
the reaction were accomplished by the reaction of a
diversified range of chroman-4-ones (1a,b) and
functionalized aromatic bisaldehydes (2a–f) under the
optimized conditions in order to obtain the corresponding
bischalcones (3a–l, Scheme 2). Interestingly, the
electronic nature of the substituents has limited impact on
the yields of the reaction, and there is a common reaction
phenomenon that bisaldehydes bearing electron-
withdrawing groups (COOH and Br) reacted a little faster
than aldehyde bearing electron-donating group (CH3).
5,50-Methylenebis(2-hydroxybenzaldehyde) (2f) is also an
efficient substrate to undergo condensation reaction with
Scheme 3. Tentative mechanism for the synthesis of 3h.
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Month 2017
Sustainable Catalytic Process with a High Eco-scale Score for the Synthesis of
Novel Series of Bischalcones through Claisen–Schmidt Condensation
chroman-4-ones (1a,b) affording the corresponding
products (3k,l) within 10 min. In next experiment, the
role of the hydroxyl group on activating the carbonyl
group of the substrate was also examined. For doing that,
a [DABCO-H][OAc] (C) was prepared [12] (Scheme 1)
and used for catalyzing the model reaction of 1b and 2d
instead of [DABCO-EtOH][AcO] (B) under optimal
conditions. It was found that the amount of product
formed decreased to 63% (Table 2, entry 8), far below
the yield catalyzed by [DABCO-EtOH][OAc] (95%)
establishing the important role of the hydroxyl group in
activating the carbonyl group (Scheme 3). All the newly
synthesized compounds were characterized by IR, NMR
spectroscopy, and high-resolution mass spectrometry.
Generally, the recyclability of IL catalyst is a very
important factor for their industrial applications. To
investigate the reusable characteristics of new synthesized
catalyst (B), recycle experiments of [DABCO-EtOH][OAc]
were tested on the aforementioned model reaction (reaction
of 1b and 2d). Once the required product had been filtered
off from the reaction mixture, IL (B) was recovered from
the aqueous solution by removing water at 70°C under
reduced pressure. The recovered IL (B) can be reused for
the next cycle even after the fifth reuse without considerable
loss of catalytic activity or stability (Fig. 1), offering a green
route to Claisen–Schmidt condensation products.
Compared with the conventional protocols (Table 1), the
strategy used can significantly reduce the reaction times,
greatly improve the reaction yields, and avert the use of
strong nonrecyclable bases or acids and organic solvents;
these merits would greatly participate in the industrially
feasible manufacturing process. Taking into consideration
the aforementioned experimental results, a reasonable
mechanistic pathway has been proposed in Scheme 3.
Initially, the lone pair of electrons of N-atom of the IL (B)
can abstract hydrogen atom from the active methylene to
form a corresponding active carbon nucleophile. On the
Figure 1. Recyclability of the catalyst. [Color figure can be viewed at
wileyonlinelibrary.com]
Scheme 4. Synthesis of bischalcones 7a–f.
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Table 3
Scaled-up synthesis of (3E,30E)-3,30-(1,4-phenylenebis(methanylylidene))bis(6-fluorochroman-4-one) (3h).
Yield (%)
96.043
CE (%)
100.000
PMI
RME (%)
88.555
E-factor
0.039
AE (%)
92.272
1.129
AE, atom economy; CE, carbon efficiency; PMI, process mass intensity; RME, reaction mass efficiency.
same time, the hydrogen-bonding interactions between the
carbonyl group of 2d and hydroxyl group of the IL (B) lead
to increase the electrophilicity of the carbonyl carbon atom.
As a result of these dual catalytic roles, the reaction
activation energy was lowered and thereby the condensation
reaction could offer excellent yield in short reaction time
(Scheme 3).
Encouraged by the obtained results of bischalcone
derivatives (3a–l) and extended of the aforementioned
study, the reaction of acetophenone (6) with bisaldehydes
(2a–f) under the same optimized conditions was also
examined (Scheme 4). All bisaldehydes used were found
to be convenient substrates for bischalcones formation.
The reaction was proceeded smoothly, completed within
15 min with excellent yield, ranging from 91% to 98%. It
is noteworthy that all products obtained are E-geometry
exclusively.
excellent yields has been designed under ultrasound
irradiation using environmentally friendly DABCO-
based IL catalyst as a promoter. The presence of α,
β-unsaturated moieties makes these molecules excellent
precursors for further synthetic renovations to meet the
need for various useful purposes. Moreover, operational
simplicity and catalyst recyclability being the major
highlight of the present method make it an attractive option
to access such bischalcone cores for parallel synthesis
applications. Further, the remarkable rate acceleration in
carrying out the reaction of insoluble substrates in aqueous
solution makes this protocol belongs to an “on water”
synthesis [11a]. The methodology reported in this study
exhibited low E-factor values and high eco-scale, which
indicated that the catalytic process adopted in this study was
eco-friendly and sustainable.
Finally, to evaluate the presented process on the
“greenness” scale, a number of green metrics such as
process mass intensity, E-factor, reaction mass efficiency,
atom economy, and carbon efficiency (CE) were studied.
Thence, the synthesis of 3h was carried out on gram-scale
(Table 3) by the reaction of 6-fluorochroman-4-one 1b
(6 mmol, 0.996 g) and terephthalaldehyde 2d (3 mmol,
0.402 g) and using 15 mol% of [DABCO-EtOH][AcO]
under ultrasound irradiation at room temperature for
10 min, which in turn provided 3h in 96% (1.238 g) yield
(Table 3). The present protocol scored a good combination
of green metrics, atom economy (92.272%), carbon
efficiency (100%), E-factor (0.039), reaction mass
efficiency (88.555%), and process mass intensity (1.129),
which makes it an ideal green and sustainable process [13].
EXPERIMENTAL
General. NMR spectra (1H and 13C) were recorded on
Bruker UltraShield spectrometer at 400 and 100 MHz,
respectively. Chemical shifts are reported in parts per
million (ppm) and are referenced to tetramethylsilane
(TMS). High-resolution mass spectra (HRMS) were
performed using
a
Bruker Daltonics microTOF
spectrometer. IR spectra were done on Perkin-Elmer
Spectrum One spectrometer. Ultrasonication was done in
a SY5200DH-T ultrasound cleaner. Melting points were
recorded on Electrothermal IA9100 melting point
apparatus (UK). Starting materials were commercially
available and were used without further purification.
Thin-layer chromatography (TLC) was performed on a
silica gel plate G (Merck 60F). By adopting the literature
precedent, bischalcones 3k, 3l, 7d [14] and 7f [15] are
prepared.
CONCLUSIONS
An efficient and eco-friendly benign synthetic protocol
Synthesis of the catalysts [DABCO-EtOH][AcO] (A).
A
toward the assembly of novel series of bischalcones in
mixture of 2-chloro-1-ethanol (0.067 mL, 1 mmol) and
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Sustainable Catalytic Process with a High Eco-scale Score for the Synthesis of
Novel Series of Bischalcones through Claisen–Schmidt Condensation
1,4-diazobicyclo[2.2.2]octane (DABCO) (0.112 g,
1 mmol) in EtOH (20 mL) was refluxed for 12 h. After
the completion of the reaction (confirmed by TLC), the
solvent was evaporated under reduced pressure, and the
intermediate A was obtained and used in the next step
without any purification. Then, sodium acetate (0.0820 g,
1 mmol) was added to a solution of A (0.192 g, 1 mmol)
in EtOH (20 mL). The mixture was refluxed for another
12 h, and the solvent was removed under reduced
pressure to give the corresponding IL catalyst (B). Yield
99%; white solid; mp = 40°C; 1H NMR (400 MHz,
DMSO): δ 3.38 (m, 6H, 3CH2), 3.23 (m, 2H, CH2), 3.16
(m, 2H, CH2), 3.03 (t, J = 6.1 Hz, 6H, 3CH2), 2.62 (s,
1H, OH), 1.61 (s, 3H, CH3). 13C NMR (100 MHz,
DMSO): δ 175.3 (CO), 67.3, 65.7, 64.7, 48.4, 26.6. IR
(KBr, cmꢀ1): νmax 3199 (OH), 1683 (C=O). HRMS (EI)
for (M + Na)+: calcd 239.1372; found 239.1414. Anal.
Calcd for C10H20N2O3: C, 55.53; H, 9.32; N, 12.95.
Found: C, 55.63; H, 9.37; N, 13.02%.
νmax 3188 (OH), 1688 (C=O). HRMS (EI) for (M)+:
calcd 460.1123; found 460.1127. Anal. Calcd for
C27H18F2O5: C, 70.43; H, 3.94. Found: C, 70.40; H,
4.06%.
(3E,30E)-3,30-((5-Bromo-2-hydroxy-1,3-phenylene)
bis(methanylylidene))bis(chroman-4-one) (3c). Yield 92%;
yellow solid; mp 320–322°C; 1H NMR (400 MHz,
DMSO): δ 11.13 (s, 1H, OH), 8.09 (s, 2H, CH), 7.75 (s,
2H, Ar–H), 7.63 (m, 2H, Ar–H), 7.30 (m, 4H, Ar–H),
7.21 (m, 2H, Ar–H), 5.37 (2, 4H, CH2). 13C NMR
(100 MHz, DMSO): δ 182.1 (CO), 161.0, 153.2, 140.3,
136.2, 135.7, 129.1, 128.5, 128.1, 122.3, 121.4, 117.5
(ArC), 67.7 (CH2). IR (KBr, cmꢀ1): νmax 3198 (OH),
1688 (C=O). HRMS (EI) for (M)+: calcd 488.0260;
found 488.0257. Anal. Calcd for C26H17BrO5: C, 63.82;
H, 3.50. Found: C, 63.78; H, 3.58%.
(3E,30E)-3,30-((5-Bromo-2-hydroxy-1,3-phenylene)
bis(methanylylidene))bis(6-fluorochroman-4-one) (3d).
Yield 95%; yellow solid; mp >400°C; 1H NMR
(400 MHz, DMSO): δ 11.19 (s, 1H, OH), 8.13 (s, 2H,
CH), 7.97 (s, 2H, Ar–H), 7.44 (m, 4H, Ar–H), 7.10 (m,
2H, Ar–H), 5.35 (2, 4H, CH2). 13C NMR (100 MHz,
DMSO): δ 182.4 (CO), 161.4, 153.1, 140.5, 136.1, 135.4,
130.3, 128.8, 128.0, 121.7, 121.4, 117.5 (ArC), 67.8
(CH2). IR (KBr, cmꢀ1): νmax 3231 (OH), 1679 (C=O).
HRMS (EI) for (M)+: calcd 524.0071; found 524.0078.
Synthesis of bischalcones (3a–l and 7a–f).
The
bisaldehydes (2a–f, 0.5 mmol), chroman-4-ones (1a,b,
1 mmol), or acetophenone (1 mmol), [DABCO-EtOH]
[AcO] (15 mol%) and deionized water (5 mL) were
introduced into a 25-mL round-bottom flask. After
stirring for 1 min at room temperature, the flask was
subjected to ultrasound irradiation (40 kHz) for 10 min.
The progress of the reaction was monitored by TLC.
After the completion of the reaction, the solid product
formed was filtered and washed with EtOH (3 × 3 mL)
and purified with recrystallization using a proper solvent.
After removal of water from the filtrate under reduced
pressure, the IL catalyst was obtained and can be reused
in the reaction five times.
Anal. Calcd for C26H15BrF2O5: C, 59.45; H, 2.88. Found:
C, 59.76; H, 2.80%.
4-Hydroxy-3,5-bis(((E)-4-oxochroman-3-ylidene)methyl)
benzoic acid (3e).
Yield 96%; yellow solid; mp 344–
1
346°C; H NMR (400 MHz, DMSO): δ 12.86 (br, s, 1H,
CO2H), 11.93 (s, 1H, OH), 8.14 (s, 2H, ArH), 7.89 (s,
2H, CH), 7.60 (m, 2H, Ar–H), 7.26 (m, 4H, Ar–H), 7.26
(m, 2H, Ar–H), 5.39 (2, 4H, CH2). 13C NMR (100 MHz,
DMSO): δ 182.3 (CO), 167.6 (CO2H), 161.1, 161.0,
157.2, 136.6, 130.5, 128.5, 126.0, 121.9, 121.4, 116.5,
114.8 (ArC), 67.6 (CH2). IR (KBr, cmꢀ1): νmax 3122 (br,
OH), 1688 (br, C=O). HRMS (EI) for (M ꢀ H)+: calcd
(3E,30E)-3,30-((2-Hydroxy-5-methyl-1,3-phenylene)
bis(methanylylidene))bis(chroman-4-one) (3a). Yield 95%;
yellow solid; mp 295–297°C; 1H NMR (400 MHz,
DMSO): δ 10.77 (s, 1H, OH), 7.88 (s, 2H, CH), 7.63 (m,
4H, Ar–H), 7.57 (s, 2H, Ar–H), 7.34 (m, 4H, Ar–H),
5.36 (s, 4H, CH2), 2.24 (s, 3H, CH3). 13C NMR
(100 MHz, DMSO): δ 182.4 (CO), 161.8, 152.0, 139.5,
136.7, 135.3, 129.1, 128.3, 127.8, 122.4, 121.7, 117.5
(ArC), 67.8 (CH2), 20.4 (CH3). IR (KBr, cmꢀ1): νmax
3164 (OH), 1691 (C=O). HRMS (EI) for (M)+: calcd
424.1310; found 424.1318. Anal. Calcd for C27H20O5: C,
76.40; H, 4.75. Found: C, 76.49; H, 4.70%.
453.0973; found 453.1026. Anal. Calcd for C27H18O7: C,
71.36; H, 3.99. Found: C, 71.39; H, 4.05%.
3,5-Bis(((E)-6-fluoro-4-oxochroman-3-ylidene)methyl)-4-
hydroxybenzoic acid (3f).
Yield 94%; yellow solid; mp
1
382–384°C; H NMR (400 MHz, DMSO): δ 12.88 (br, s,
1H, CO2H), 12.01 (s, 1H, OH), 8.13 (s, 2H, ArH), 7.84
(s, 2H, CH), 7.62 (m, 4H, Ar–H), 7.21 (m, 2H, Ar–H),
5.30 (s, 4H, CH2). 13C NMR (100 MHz, DMSO): δ
182.6 (CO), δ 167.9 (CO2H), 160.6, 160.1, 157.5, 156.9,
136.2, 130.8, 128.3, 125.7, 121.3, 117.2, 115.6 (ArC),
67.7 (CH2). IR (KBr, cmꢀ1): νmax 3117 (br, OH), 1689,
1675 (C=O). HRMS (EI) for (M ꢀ H)+: calcd 489.0785;
found 489.0781. Anal. Calcd for C27H16F2O7: C, 66.13;
H, 3.29. Found: C, 66.04; H, 3.33%.
(3E,30E)-3,30-((2-Hydroxy-5-methyl-1,3-phenylene)
bis(methanylylidene))bis(6-fluorochroman-4-one) (3b).
Yield 93%; yellow solid; mp >400°C; 1H NMR
(400 MHz, DMSO): δ 10.86 (s, 1H, OH), 8.11 (s, 2H,
CH), 7.77 (m, 4H, Ar–H), 7.58 (s, 2H, Ar–H), 7.39 (m,
2H, Ar–H), 5.33 (2, 4H, CH2), 2.26 (s, 3H, CH3). 13C
NMR (100 MHz, DMSO): δ 182.7 (CO), 161.0, 157.7,
152.4, 140.8, 136.4, 135.7, 129.5, 129.2, 127.3, 121.2,
117.9 (ArC), 67.9 (CH2), 20.5 (CH3). IR (KBr, cmꢀ1):
(3E,30E)-3,30-(1,4-Phenylenebis(methanylylidene))
bis(chroman-4-one) (3g).
Yield 95%; yellow solid; mp
253–255°C; 1H NMR (400 MHz, DMSO): δ 8.12 (m,
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W. A. A. Arafa
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2H, ArH), 7.89 (s, 2H, CH), 7.51 (m, 2H, Ar–H), 7.33 (m,
2H, Ar–H), 7.26 (s, 4H, Ar–H), 6.98 (d, J = 8.1 Hz, 2H,
Ar–H), 5.35 (d, J = 1.5 Hz, 4H, CH2). 13C NMR
(100 MHz, DMSO): δ 182.3 (CO), 161.6, 137.2, 136.4,
135.0, 131.4, 130.5, 128.6, 122.3, 122.0, 118.2 (ArC),
67.8 (CH2). IR (KBr, cmꢀ1): νmax 1689 (C=O). HRMS
(EI) for (M)+: calcd 394.1207; found 394.1203. Anal.
Calcd for C26H18O4: C, 79.17; H, 4.60. Found: C, 79.11;
128.1, 127.6, 119.5 (ArC), 20.6 (CH3). IR (KBr, cmꢀ1):
νmax 3199 (OH), 1668 (C=O). HRMS (EI) for (M)+:
calcd 368.1413; found 368.1416. Anal. Calcd for
C25H20O3: C, 81.50; H, 5.47. Found: C, 81.59; H, 5.38%.
(2E,20E)-3,30-(5-Bromo-2-hydroxy-1,3-phenylene)bis(1-
phenylprop-2-en-1-one) (7b). Yield 95%; yellow solid; mp
207–209°C; 1H NMR (400 MHz, DMSO): δ 10.90 (s, 1H,
OH), 8.05 (d, J = 15.7 Hz, 2H, CH, β-H), 7.80 (d,
J = 15.7 Hz, 2H, CH, α-H), 7.75 (s, 2H, Ar–H), 7.68 (m,
4H, Ar–H), 7.40 (m, 6H, Ar–H). 13C NMR (100 MHz,
DMSO): δ 189.9 (C=O), 143.7 (Cβ, Cβ`), 123.8 (Cα,
Cα`), 154.2, 139.0, 135.3, 130.9, 129.6, 128.6, 118.7,
111.6 (ArC). IR (KBr, cmꢀ1): νmax 3214 (OH), 1664
(C=O). HRMS (EI) for (M)+: calcd 432.0360; found
432.0364. Anal. Calcd for C24H17BrO3: C, 66.53; H,
H, 4.69%.
3E,30E)-3,30-(1,4-Phenylenebis(methanylylidene))bis(6-
fluorochroman-4-one) (3h). Yield 95%; yellow solid; mp
1
297–300°C; H NMR (400 MHz, DMSO): δ 7.92 (s, 2H,
CH), 7.50 (m, 4H, Ar–H), 7.27 (s, 4H, Ar–H), 7.08 (s,
2H, Ar–H), 5.36 (d, J = 1.6 Hz, 4H, CH2). 13C NMR
(100 MHz, DMSO): δ 182.4 (CO), δ 161.3, 139.2, 137.4,
136.2, 135.4, 131.3, 130.4, 129.6 128.4, 122.2, 118.1
(ArC), 67.7 (CH2). IR (KBr, cmꢀ1): νmax 1695 (C=O).
HRMS (EI) for (M)+: calcd 430.1015; found 430.1018.
Anal. Calcd for C26H16F2O4: C, 72.56; H, 3.75. Found:
3.95. Found: C, 66.50; H, 4.04%.
4-Hydroxy-3,5-bis((E)-3-oxo-3-phenylprop-1-en-1-yl)benzoic
1
acid (7c). Yield 93%; yellow solid; mp 198–200°C; H
NMR (400 MHz, DMSO): δ 13.21 (br, s, 1H, CO2H),
11.96 (s, 1H, OH), 8.17 (s, 2H, ArH), 8.08 (d,
J = 15.7 Hz, 2H, CH, β-H), 7.88 (d, J = 15.7 Hz, 2H,
CH, α-H), 7.50 (m, 6H, Ar–H), 7.72 (m, 4H, ArH). 13C
NMR (100 MHz, DMSO): δ 189.8 (C=O), 169.7
(COOH), 143.9 (Cβ, Cβ`), 123.6 (Cα, Cα`), 160.1, 138.7,
134.7, 130.3, 129.6, 128.6, 128.3, 122.5 (ArC). IR (KBr,
cmꢀ1): νmax 3254 (br, OH), 1688, 1675 (2C=O). HRMS
(EI) for (M ꢀ H)+: calcd 397.1077; found 397.1070.
Anal. Calcd for C25H18O5: C, 75.37; H, 4.55. Found: C,
C, 72.61; H, 3.71%.
(3E,30E)-3,30-((1H-Pyrazole-3,5-diyl)bis(methanylylidene))
bis(chroman-4-one) (3i). Yield 90%; white solid; mp 283–
285°C; 1H NMR (400 MHz, DMSO): δ 14.21 (s, 1H, NH),
8.04 (m, 2H, Ar–H), 7.88 (s, 2H, CH), 7.32 (m, 2H, Ar–H),
7.18 (s, 1H, Pyrazole-C4), 7.12 (m, 2H, Ar–H), 6.98 (m,
2H, Ar–H), 5.40 (s, 4H, CH2). 13C NMR (100 MHz,
DMSO): δ 182.1(CO), 161.5, 137.5, (Ar–C), 135.7
(Pyrazole-C3), 134.7, 30.2, 129.5, 128.6, 122.04, 118.4,
(Ar–C), 109.2, (Pyrazole-C4), 67.7 (CH2). IR (KBr,
cmꢀ1): νmax 3166 (br, NH), 1689 (C=O). HRMS (EI) for
(M ꢀ H)+: calcd 383.1033; found 383.1037. Anal. Calcd
for C23H16N2O4: C, 71.87; H, 4.20; N, 7.29. Found: C,
75.27; H, 4.59%.
(2E,20E)-3,30-(1H-Pyrazole-3,5-diyl)bis(1-phenylprop-2-en-
1
1-one) (7e). Yield 94%; white solid; mp 218–221°C; H
NMR (400 MHz, DMSO): δ 14.23 (s, 1H, NH), 8.05 (d,
J = 15.5 Hz, 2H, CH, β-H), 7.87 (m, 4H, Ar–H), 7.75 (d,
J = 15.6 Hz, 2H, CH, α-H), 7.53 (m, 6H, Ar–H), 7.20 (s,
1H, Pyrazole-C4). 13C NMR (100 MHz, DMSO): δ 188.9
(C=O), 143.6 (Cβ, Cβ`), 123.3 (Cα, Cα`), 137.9, 134.7,
129.4, 128.6, 127.5 (Ar–C), 135.9 (Pyrazole-C3), 109.2,
(Pyrazole-C4). IR (KBr, cmꢀ1): νmax 3184 (br, NH), 1669
(C=O). HRMS (EI) for (M)+: calcd 328.1213; found
328.1219. Anal. Calcd for C21H16N2O2: C, 76.81; H,
4.91; N, 8.53. Found: C, 76.88; H, 4.91; N, 8.48%.
71.80; H, 4.31; N, 7.35%.
(3E,30E)-3,30-((1H-Pyrazole-3,5-diyl)bis(methanylylidene))
bis(6-fluorochroman-4-one) (3j). Yield 91%; white solid;
1
mp 315–318°C; H NMR (400 MHz, DMSO): δ 14.11
(s, 1H, NH), 7.89 (s, 2H, CH), 7.34 (m, 2H, Ar–H), 7.30
(m. 2H, Ar–H), 7.17 (s, 1H, Pyrazole-C4), 7.06 (m, 2H,
Ar–H), 5.38 (s, 4H, CH2). 13C NMR (100 MHz, DMSO):
δ 182.6 (CO), 161.8, 160.5, 137.3 (Ar–C), 135.3
(Pyrazole-C3), 132.3, 129.8, 128.5, 121.8, 118.7, (Ar–C),
109.4, (Pyrazole-C3), 67.9 (CH2). IR (KBr, cmꢀ1): νmax
3174 (br, NH), 1686 (C=O). HRMS (EI) for (M ꢀ H)+:
calcd 419.0844; found 419.0840. Anal. Calcd for
C23H14F2N2O4: C, 65.72; H, 3.36; N, 6.66. Found: C,
65.85; H, 3.42; N, 6.69%.
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