Green synthesis of dissymmetric bisarylidene derivatives of cyclohexanone analogues under ultrasonic conditions

Article abstract of DOI:10.1007/s13738-018-1498-5

Abstract: A new procedure is developed for the synthesis of dissymmetric bisarylidene derivatives of two cyclohexanone analogues. Under mild ultrasonic/organocatalytic conditions, the first aldehyde reacts with the ketone to give the monoarylidene intermediate which subsequently condenses with the second aldehyde upon addition of NaOH/MeOH to the reaction mixture. Both condensations proceed in one pot, and high yields of the corresponding products are obtained in relatively short time periods. It was shown that the method is useful for the synthesis of monoarylidene counterparts as well. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s13738-018-1498-5

Journal of the Iranian Chemical Society
https://doi.org/10.1007/s13738-018-1498-5
ORIGINAL PAPER
Green synthesis of dissymmetric bisarylidene derivatives
of cyclohexanone analogues under ultrasonic conditions
Mohammad M. Mojtahedi1 · Leila Afshinpoor1 · Fatemeh Karimi1 · M. Saeed Abaee1
Received: 26 May 2018 / Accepted: 10 September 2018
© Iranian Chemical Society 2018
Abstract
A new procedure is developed for the synthesis of dissymmetric bisarylidene derivatives of two cyclohexanone analogues.
Under mild ultrasonic/organocatalytic conditions, the first aldehyde reacts with the ketone to give the monoarylidene inter-
mediate which subsequently condenses with the second aldehyde upon addition of NaOH/MeOH to the reaction mixture.
Both condensations proceed in one pot, and high yields of the corresponding products are obtained in relatively short time
periods. It was shown that the method is useful for the synthesis of monoarylidene counterparts as well.
Graphical abstract
Keywords Green synthesis · Dissymmetric bisarylidenes · Aldol condensation · One-pot reaction · Sonochemistry
Introduction
Bisarylidenes belong to chalcones [6] and are usually
synthesized through aldol condensations [7]. These com-
pounds are synthetically interesting due to exhibiting diverse
biological [8, 9], medicinal [10, 11], and industrial [12]
properties. In addition, bisarylidenes are known for their
liquid crystal [13, 14], dye [15, 16], data storage [17], and
optical [18] applications. They are also employed as useful
intermediates in other synthetic transformations [19, 20].
Consequently, several procedures are developed for the syn-
thesis of bisarylidenes of various cyclic [21, 22] and acyclic
ketones [23–25]. Despite these developments, efficient syn-
thesis of monoarylidene and dissymmetric derivatives still
remains of great challenge.
Sonochemistry has witnessed an overwhelming growth
in recent years due to the enhancement observed in rates,
yields, and selectivity of the reactions to access the desired
compounds more efficiently [1, 2]. This enhancement is
often attributed to cavitation caused by ultrasound irradia-
tion of the solutions forming small bubbles [3]. Upon col-
lapse of the bubbles, highly concentrated local heating and
pressure provide the required energy of the reactions [4, 5].
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s13738-018-1498-5) contains
supplementary material, which is available to authorized users.
In the framework of our studies on aldol condensation
reaction [26, 27], we have reported several procedures
for the synthesis of bisarylidene derivatives of various
homocyclic [28, 29] and heterocyclic [30] systems. We
also developed efficient procedures for preparation of the
monoarylidene counterparts [31] and their application
in the synthesis of more complex products [32]. On this
* Mohammad M. Mojtahedi
mojtahedi@ccerci.ac.ir
1
Chemistry and Chemical Engineering Research Center
of Iran, P.O.Box 14335-186, Tehran, Iran
Vol.:(0123456789)
1 3

Journal of the Iranian Chemical Society
track, we were persuaded to devise a method for efficient
synthesis of dissymmetric bisarylidenes. These com-
pounds are interesting because of their various medicinal
and biological properties [33–37].
Experimental
General
The difficulty for preparation of mono- and dissymmet-
ric bisarylidene derivatives is due to preferred formation
of the symmetric bis counterparts. The reason is that the
acidity of the α-hydrogens of the starting ketone and that
of the initially formed monoarylidene product are very
comparable. Therefore, this leads to two competitive aldol
condensation reactions with very similar rates. As a result,
one can conclude that selective synthesis of mono- and
dissymmetric bisarylidene derivatives is achievable if the
conditions would discriminate between α-deprotonation of
the starting ketone and that of the monoarylidene interme-
diate. Consequently, the main product of such a selective
process would be the monoarylidene moiety which can
be either separated from the reaction mixture or is further
reacted with a second aldehyde to access the dissymmetric
bisarylidene counterpart.
Reactions were monitored by TLC using silica gel-coated
plates and EtOAc/petroleum ether solutions as the mobile
phase. Melting points are uncorrected. FT-IR spectra were
recorded using KBr disks on a Bruker Vector-22 infrared
spectrometer and absorptions are reported as wave num-
bers (cm− 1). NMR spectra were obtained on an FT-NMR
Bruker UltraShield™ (500 MHz) or Bruker Avance (250 or
400 MHz) spectrometers as CDCl3 solutions and the chemi-
cal shifts are expressed as δ units with Me4Si as the internal
standard. Mass spectra were obtained on a Finnigan Mat
8430 apparatus at ionization potential of 70 eV. Elemental
analyses were performed using a Thermo Finnigan Flash
EA 1112 instrument. Reagents and starting materials were
purchased from commercial sources and were freshly used
after being purified by standard procedures. Products 3 and 5
were known and their identity was confirmed by comparing
their 1H NMR spectra with those of reported ones. Products
Literature shows that usually aldol condensation of
ketones leads to synthesis of symmetrical bisarylidenes
[38] and methods for efficient preparation of mono- and
dissymmetric bisarylidenes are rare. Additionally, many of
these methods are limited by using excessive reagents [33,
35, 39], giving low yields of target products [34, 35, 40],
proceeding under undesired conditions [41], and requir-
ing stepwise operations [42]. Here, we introduce a path-
way for efficient one-pot synthesis of dissymmetric bisar-
ylidenes. Primarily, an organocatalyst gives the respective
monoarylidenes which further reacts in situ with a second
aldehyde upon switching to stronger basic conditions. As
an additional consequence, the method is also used for
convenient synthesis of the monoarylidene derivatives by
stopping the process midway (Scheme 1).
4 were new and were characterized by their 1H NMR, 13
C
NMR, IR, and mass spectra and their purity was confirmed
by elemental analyses.
General procedure for the synthesis of 4
A mixture of ketone 1 (1.0 mmol) and pyrrolidine (63 µL,
75 mol%) was sonicated for 2 min. To this mixture, an alde-
hyde (RCHO; 1.0 mmol) was added and the mixture was
sonicated until TLC (EtOAc/hexanes 1:4) showed maximum
formation of the respective monoarylidene intermediate. At
this point, the second aldehyde (R’CHO; 1.0 mmol), NaOH
(2 mL, 10%), and MeOH (5 mL) were added and the result-
ing mixture was sonicated until TLC showed completion
of the process. The reaction mixture was diluted in EtOAc.
The organic layer was washed with saturated NH4Cl and
dried over Na2SO4. The product was obtained by column
chromatography.
O
X
O
X
R
R
R
1a
1b
: X = NMe
: X = CH2
Characterization of new products
5
4
a) RCHO
3‑((E)‑Benzylidene)‑5‑((E)‑4‑chlorobenzylidene)‑1‑me
thylpiperidin‑4‑one (4a)
O
X
O
X
Yellow crystals; mp = 170–172 °C; IR (KBr) 2773, 1670,
1607 cm− 1; 1H NMR (400 MHz, CDCl3): δ 2.46 (s, 3H),
3.73 (s, 2H), 3.77 (s, 2H), 7.32 (d, J=8.5 Hz, 2H), 7.35–7.44
(m, 7H), 7.75 (s, 1H), 7.82 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 44.9, 56.0, 56.1, 127.5, 127.8, 128.1, 129.4, 130.5,
131.9, 132.5, 132.6, 133.9, 134.0, 134.1, 135.6, 185.7;
b) R'CHO
R
R'
3
Scheme 1 Competitive pathways leading to selective synthesis of 3,
4, or 5
1 3

Journal of the Iranian Chemical Society
MS (70 eV) m/z 323 [M+], 294, 178, 149; Anal. Calcd for
C20H18ClNO: C, 74.18; H, 5.60; N, 4.33. Found: C, 74.23;
H, 5.49; N, 4.38.
136.6, 160.5, 187.0; MS (70 eV) m/z 319 [M+], 304, 260,
244; Anal. Calcd for C21H21NO2: C, 78.97; H, 6.63; N, 4.39.
Found: C, 79.11; H, 6.56; N, 4.44.
3‑((E)‑Benzylidene)‑1‑methyl‑5‑((E)‑4‑nitrobenzylidene)
3‑((E)‑4‑Bromobenzylidene)‑5‑((E)‑4‑chlorobenzylidene)‑1‑
piperidin‑4‑one (4b)
methylpiperidin‑4‑one (4f)
Yellow crystals; mp=138−135 °C; IR (KBr) 2780, 1672,
1613 cm−1; 1H NMR (500 MHz, CDCl3) δ 2.47 (s, 3H), 3.73
(s, 2H), 3.79 (s, 2H), 7.37–7.45 (m, 5H), 7.52 (d, J=8.5 Hz,
Yellow crystals; mp = 181–183 °C; IR (KBr) 1747, 1672,
1650 cm− 1; 1H NMR (500 MHz, CDCl3) δ 2.47 (s, 3H),
3.72 (s, 2H), 3.73 (s, 2H), 7.25 (d, J=8.5 Hz, 2H), 7.32 (d,
J=8.5 Hz, 2H), 7.40 (d, J=8.5 Hz, 2H), 7.55 (d, J=8.5 Hz,
2H), 7.73 (s, 1H), 7.75 (s, 1H); 13C NMR (125 MHz, CDCl3)
δ 46.1, 57.2, 123.6, 129.1, 131.7, 131.9, 132.0, 133.6, 133.7,
133.8, 134.2, 135.3, 135.4, 186.6; MS (70 eV) m/z 401 [M+],
374, 222, 178, 115; Anal. Calcd for C20H17BrClNO: C,
59.65; H, 4.25; N, 3.48. Found: C, 59.75; H, 4.32; N, 3.40.
2H), 7.79 (s, 1H), 7.83 (s, 1H), 7.27 (d, J=8.5 Hz, 2H); 13
C
NMR (125 MHz, CDCl3) δ 46.0, 57.0, 57.2, 123.9, 128.8,
129.5, 130.7, 130.9, 132.7, 133.4, 135.1, 136.4, 137.6,
141.9, 147.6, 186.5; MS (70 eV) m/z 334 [M+], 305, 215,
143, 115; Anal. Calcd for C20H18N2O3: C, 71.84; H, 5.43;
N, 8.38. Found: C, 71.88; H, 5.60; N, 8.44.
3‑((E)‑Benzylidene)‑5‑((E)‑4‑fluorobenzylidene)‑1‑methyl‑
3‑((E)‑4‑Chlorobenzylidene)‑5‑((E)‑2‑fluorobenzylidene)‑
piperidin‑4‑one (4c)
1‑methylpiperidin‑4‑one (4g)
Yellow crystals; mp = 121–123 °C; IR (KBr) 2780, 1672,
1613, 1506 cm− 1; 1H NMR (500 MHz, CDCl3) δ 2.47 (s,
3H), 3.76 (s, 2H), 3.79 (s, 2H), 7.11 (dd, J = 8.5, 8.5 Hz,
2H), 7.37–7.44 (m, 7H), 7.78 (s, 1H), 7.83 (s, 1H); 13C NMR
(125 MHz, CDCl3) δ 46.1, 57.3, 57.4, 116.2 (d, J=21.4 Hz),
129.0, 129.5, 130.8, 131.7, 131.8, 132.8 (d, J = 8.4 Hz),
133.1 (d, J = 19.0 Hz), 135.6, 135.8, 137.2, 163.3 (d,
J=249.4 Hz), 187.0; MS (70 eV) m/z 307 [M+], 306, 228,
210, 115; Anal. Calcd for C20H18FNO: C, 78.15; H, 5.90; N,
4.56. Found: C, 78.22; H, 5.98; N, 4.48.
Yellow crystals; mp = 110–112 °C; IR (KBr) 2930, 1727,
1672, 1613 cm− 1; 1H NMR (500 MHz, CDCl3) δ 2.44 (s,
3H), 3.66 (s, 2H), 3.75 (s, 2H), 7.11(ddd, J=0.6, 9.0, 9.5,
Hz, 1H), 7.18 (dd, J = 7.5, 7.5 Hz, 1H), 7.26–7.28 (m,
1H), 7.30 (d, J = 8.5 Hz, 2H), 7.32–7.37 (m, 1H), 7.39
(d, J = 8.5 Hz, 2H), 7.77 (s, 1H), 7.90 (s, 1H); 13C NMR
(125 MHz, CDCl3) δ 46.0, 57.1, 57.5, 116.3 (d, J=22.0 Hz),
123.5 (d, J=14.0 Hz), 124.4 (d, J=3.5 Hz), 129.3, 129.9,
131.1 (d, J = 2.5 Hz), 131.4 (d, J = 8.5 Hz), 132.0, 133.5,
134.0, 134.8, 135.6, 136.1, 161.3 (d, J = 250 Hz), 186.5;
MS (70 eV) m/z 341 [M+], 340, 343, 244; Anal. Calcd for
C20H17ClFNO: C, 70.28; H, 5.01; N, 4.10. Found: C, 70.12;
H, 5.10; N, 4.01.
(E)‑3‑((E)‑Benzylidene)‑1‑methyl‑5‑((E)‑3‑phenylallylidene)
piperidin‑4‑one (4d)
Yellow solid; mp = 99–101 °C; IR (KBr) 2783, 1662,
1603 cm− 1; 1H NMR (400 MHz, CDCl3): δ 2.51 (s, 3H),
3.69 (s, 2H), 3,73 (s, 2H), 6.96–7.04 (m, 2H), 7.32–7.52
(m, 11H), 7.81 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3)
δ 44.9, 54.6, 55.8, 121.5, 126.3, 127.5, 127.8, 127.9, 128.2,
129.4, 130.9, 132.0, 134.3, 134.8, 135.1, 135.3, 140.9,
185.4 ppm; MS (70 eV) m/z 315 [M+], 224, 171, 142; Anal.
Calcd for C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C,
83.87; H, 6.83; N, 4.37.
3‑((E)‑4‑Chlorobenzylidene)‑1‑methyl‑5‑((E)‑4‑nitroben‑
zylidene)piperidin‑4‑one (4h)
Yellow crystals; mp = 161–163 °C; IR (KBr) 2723, 1674,
1594, 1513 cm− 1; 1H NMR (500 MHz, CDCl3) δ 2.49 (s,
3H), 3.77 (s, 2H), 3.79 (s, 2H), 7.33 (d, J = 8.0 Hz, 2H),
7.40 (d, J=8.0 Hz, 2H), 7.52 (d, J=8.5 Hz, 2H), 7.77 (s,
1H), 7.81 (s, 1H), 8.27 (d, J=8.5 Hz, 2H) ppm; 13C NMR
(125 MHz, CDCl3) δ 46.0, 57.0, 57.2, 124.2, 127.0, 129.4,
129.5, 132.0, 132.1, 132.3, 133.7, 136.0, 136.7, 141.9,
148.0, 186.3 ppm; MS (70 eV) m/z 368 [M+], 340, 215,
178; Anal. Calcd for C20H17ClN2O3: C, 65.13; H, 4.65; N,
7.60. Found: 65.01; H, 4.52; N, 7.62.
3‑((E)‑Benzylidene)‑5‑((E)‑4‑methoxybenzylidene)‑1‑meth‑
ylpiperidin‑4‑one (4e)
Yellow crystals; mp = 119–121 °C; IR (KBr) 2775 1671,
1603 cm−1; 1H NMR (500 MHz, CDCl3) δ 2.47 (s, 3H), 3.76
(s, 2H), 3.78 (s, 2H), 3.85 (s, 3H), 6.95 (d, J=8.5 Hz, 2H),
7.35–7.44 (m, 7H), 7.79 (s, 1H), 7.82 (s, 1H); 13C NMR
(125 MHz, CDCl3) δ 46.0, 55.5, 57.1, 57.5, 114.3, 128.1,
128.7, 129.1, 130.5, 131.3, 132.6, 133.4, 135.5, 136.2,
(E)‑3‑((E)‑4‑Chlorobenzylidene)‑1‑methyl‑5‑((E)‑3‑phenylal‑
lylidene)piperidin‑4‑one (4i)
Yellow crystals; mp = 162–164 °C; IR (KBr) 3026, 1667,
1611, 1571 cm− 1; 1H NMR (500 MHz, CDCl3) δ 2.51 (s,
1 3

Journal of the Iranian Chemical Society
3H), 3.68 (s, 4H), 6.96 (dd, J=11.3, 15.3 Hz, 1H), 7.02 (d,
J = 15.3 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 7.32–7,34 (m,
1H), 7.37–7.39 (m, 4H), 7.47 (d, J=11.3 Hz, 1H), 7.50–7.52
(m, 2H), 7.73 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ
46.3, 56.0, 57.2, 123.0, 127.8, 129.2, 129.3, 129.7, 132.0,
132.2, 134.0, 134.2, 135.0, 135.3, 136.4, 136.8, 142.6,
186.5 ppm; MS (70 eV) m/z 349 [M+], 258, 196, 141; Anal.
Calcd for C22H20ClNO: C, 75.53; H, 5.76; N, 4.00. Found:
C, 75.66; H, 5.69; N, 4.08.
3‑((E)‑4‑Fluorobenzylidene)‑1‑methyl‑5‑((E)‑4‑methylben‑
zylidene)piperidin‑4‑one (4m)
Yellow crystals; mp = 158–160 °C; IR (KBr) 2780, 1670,
1609, 1579, 1507 cm− 1; 1H NMR (500 MHz, CDCl3) δ
2.39 (s, 3H), 2.47 (s, 3H), 3.73 (s, 2H), 3.77 (s, 2H), 7.11
(dd, J=8.5, 8.5 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 7.30 (d,
J=8.0 Hz, 2H), 7.38 (dd, J=5.6, 8.5 Hz, 2H), 7.76 (s, 1H),
7.80 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 21.9,
46.3, 57.4, 57.6, 116.1 (d, J=21.6 Hz), 129.8, 131.0, 131.9
(d, J = 3.6 Hz), 132.7, 132,8, 132.8, 133.4, 135.4, 137.1,
139.9, 163.3 (d, J=250 Hz), 187.2 ppm; MS (70 eV) m/z
321 [M+], 320, 229; Anal. Calcd for C21H20FNO: C, 78.48;
H, 6.27; N, 4.36. Found: C, 78.40; H, 6.33; N, 4.32.
3‑((E)‑4‑Chlorobenzylidene)‑5‑((E)‑4‑methoxybenzylidene)‑
1‑methylpiperidin‑4‑one (4j)
Yellow crystals; mp = 165–167 °C; IR (KBr) 2725, 1667,
1604, 830 cm−1; 1H NMR (500 MHz, CDCl3) δ 2.48 (s, 3H),
3.75 (s, 2H), 3.80 (s, 2H), 3.85 (s, 3H), 6.94 (d, J=8.5 Hz,
2H), 7.30 (d, J=8.5 Hz, 2H), 7.36 (d, J=8.0 Hz, 2H), 7.38
(d, J=8.0 Hz, 2H),7.75 (s, 1H), 7.79 (s, 1H) ppm; 13C NMR
(125 MHz, CDCl3) δ 46.0, 55.8, 57.1, 57.5, 114.6, 128.1,
128.3, 129.3, 132.0, 132.9, 134.0, 134.1, 135.4, 138.4,
160.9, 187.0 ppm; MS (70 eV) m/z 353 [M+], 277, 278,
133, 115; Anal. Calcd for C21H20ClNO2: C, 71.28; H, 5.70;
N, 3.96. Found: C, 71.11; H, 5.77; N, 4.01.
2‑((E)‑4‑Chlorobenzylidene)‑6‑((E)‑2,4‑dimethoxyben‑
zylidene)cyclohexan‑1‑one (4n)
Yellow solid; mp=143–144 °C; IR (KBr) 2948, 1658, 1600,
1492 cm− 1; 1H NMR (250 MHz, CDCl3) δ 1.75–1.85 (m,
2H), 2.85–2.85–2.91 (m, 4H), 3.86 (s, 6H), 6.51 (s, 1H),
6.54 (d, J=8.0 Hz, 1H), 7.28–7.23 (m, 1H), 7.38–7.40 (m,
4H), 7.73 (s, 1H), 8.03 (s, 1H); 13C NMR (63 MHz, CDCl3)
δ 23.3, 28.6, 28.7, 55.4, 55.5, 98.2, 104.2, 117.9, 128.6,
131.3, 131.5, 132.7, 134.2, 134.3, 134.7, 134.9, 137.1,
160.1, 161.8, 190.1 ppm; MS (70 eV) m/z: 368 [M+], 340,
285, 210; Anal. Calcd for C22H21ClO3: C, 71.64; H, 5.74.
Found: C, 71.75; H, 5.79.
(E)‑3‑((E)‑4‑Chlorobenzylidene)‑5‑(furan‑2‑ylmethylene)‑1‑
methylpiperidin‑4‑one (4k)
Yellow crystals; mp=121–123 °C; IR (KBr); 2789, 1668,
1614, 1544 cm−1; 1H NMR (500 MHz, CDCl3): δ 2.51 (s,
3H), 3.70 (s, 2H), 3.93 (s, 2H), 6.53 (d,d, J = 1.5, 3.5 Hz,
1H), 6.68 (d, J=3.5 Hz, 1H), 7.28 (d, J=8.5 Hz, 2H), 7.37
(d, J=8.5 Hz, 2H), 7.51 (s, 1H), 7.59 (d, J=1.5 Hz, 1H),
7.74 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 46.0, 56.7,
57.1, 112.7, 117.5, 122.6, 129.0, 130.0, 131.7, 133.8, 133.9,
134.6, 135.1, 145.5, 152.3, 186.5 ppm; MS (70 eV) m/z 313
[M+], 284, 172, 125; Anal. Calcd for C18H16ClNO2: C,
68.90; H, 5.14; N, 4.46. Found: C, 68.79; H, 5.21; N, 4.50.
2‑((E)‑2,4‑Dichlorobenzylidene)‑6‑((E)‑4‑methylben‑
zylidene)cyclohexan‑1‑one (4o)
Yellow crystals; mp = 122–124 °C: IR (KBr) 2939, 1660,
1600, 1458 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.68–1.71
(m, 2H), 2.30 (s, 3H), 2.63–2.65 (m, 2H), 2.84–2.86 (m,
2H), 7.13 (d, J=8.0 Hz, 2H), 7.15–7.18 (m, 3H), 7.29 (d,
J = 8.0 Hz, 2H), 7.37(s, 1H), 7.72 (s, 1H) ppm; 13C NMR
(100 MHz, CDCl3) δ 21.5, 23.1, 28.2, 28.7, 126.7, 129.2,
129.6, 130.6, 131.2, 132.1, 133.0, 133.1, 134.6, 135.0,
135.7, 138.0, 138.5, 139.2, 189.8 ppm; MS (70 eV) m/z:
356, [M+], 342, 322, 279, 115; Anal. Calcd for C21H18Cl2O:
C, 70.60; H, 5.08. Found: C, 70.67; H, 5.11.
(E)‑3‑((E)‑4‑Chlorobenzylidene)‑1‑methyl‑5‑(thiophen‑2‑yl‑
methylene)piperidin‑4‑one (4l)
(E)‑2‑((E)‑4‑Methylbenzylidene)‑6‑((E)‑3‑phenylallylidene)
cyclohexan‑1‑one (4p)
Yellow crystals; mp = 112–114 °C; IR (KBr) 2940, 1665,
1605, 1571 cm− 1; 1H NMR (500 MHz, CDCl3) δ 2.53 (s,
3H), 3.73 (s, 2H), 3.81 (s, 2H), 7.16 (dd, J = 4.0, 5.0 Hz,
1H), 7.27 (d, J=8.5 Hz, 2H), 7.34 (d, J=4.0 Hz, 1H), 7.38
(d, J=8.5 Hz, 2H), 7.57 (d, J=5.0 Hz, 1H), 7.75 (s, 1H),
7.94 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δ 46.2, 56.7,
57.5, 128.5, 129.3, 129.6, 130.3, 131.2, 131.9, 133.8, 134.1,
135.2, 135.4, 139.0, 186.5 ppm; MS (70 eV) m/z 329 [M+],
245, 216; Anal. Calcd for C18H16ClNOS: C, 65.55; H, 4.89;
N, 4.25. Found: C, 65.34; H, 4.95; N, 4.12.
Yellow solid; mp 138–139 °C; IR (KBr): 2939, 1658,
1592, 1448 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.73–1.78
(m, 2H), 2.31 (s, 3H), 2.73–2.76 (m, 2H), 2.82–2.84 (m,
2H), 6.91 (d, J=16.0 Hz, 1H), 7.02 (dd, J=8.0, 16.0 Hz,
1H), 7.13 (d, J=8.0 Hz, 2H), 7.18–7.30 (m, 6H), 7.43 (d,
J = 8.0 Hz, 2H), 7.69 (s, 1H) ppm; 13C NMR (100 MHz,
CDCl3) δ 21.4, 22.5, 26.7, 28.4, 123.7, 127.2, 128.8, 128.9,
1 3

Journal of the Iranian Chemical Society
129.1, 130.5, 133.2, 135.4, 135.5, 136.5, 136.7, 136.8,
138.8, 140.8, 189.7 ppm; MS (70 eV) m/z : 314 [M+], 299,
223, 115. Anal. Calcd for C23H22O: C, 87.86; H, 7.05.
Found: C, 87.95; H, 6.97.
128.4, 129.1, 130.2, 130.6, 133.0, 133.1, 133.2, 133.6,
135.4, 136.5, 136.8, 137.2, 138.9, 190.4 ppm; MS (70 eV)
m/z: 338 [M+], 323, 281, 165; Anal. Calcd for C25H22O:
C, 88.72; H, 6.55. Found: C, 88.63; H, 6.22.
2‑((E)‑4‑Chlorobenzylidene)‑6‑((E)‑2,4‑dichloroben‑
zylidene)cyclohexan‑1‑one (4q)
X‑ray crystal structure analysis of 4k
Yellow solid; mp 130–132 °C; IR (KBr): 2938, 1660,
1458 cm− 1; 1H NMR (400 MHz, CDCl3) δ 1.68–1.70 (m,
2H), 2.63–2.64 (m, 2H), 2.79–2.80 (m, 2H), 7.16–7.17 (m,
2H), 7.28–7.30 (m, 4H), 7.37 (s, 1H), 7.66 (s, 1H), 7.72
(s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 22.9, 28.2,
28.6, 126.8, 128.7, 129.7, 131.2, 131.7, 132.5, 132.9, 134.2,
134.7, 134.8, 135.8, 136.2, 136.4, 138.2, 189.5 ppm; Mass
(70 eV) m/z (%): 376 [M+], 343, 342, 115; Anal. Calcd for
C20H15Cl3O: C, 63.60; H, 4.00. Found: C, 63.52; H, 4.05.
The X-ray diffraction measurements were carried out on
STOE IPDS-2T diffractometers with graphite-monochro-
mated Mo(Kα) radiation. All single crystals were mounted
on a glass fiber and used for data collection. Yellow single
crystals of compound 4k, suitable for SC-XRD measure-
ment were grown by slow evaporation of EtOH solution.
The structure was solved by direct method and refined by
full matrix least-squares calculations based on F2 to final
R1=0.0426, wR2 (all data)=0.0553, using SHELXL-2014
and WinGX-2013.3 programs [43–48]. Compound is crys-
tallized at orthorhombic crystal system and P212121 space
group. One independent molecules with molecular formula
of C18H16ClNO2 was found in the asymmetric unit, giving a
total Z = 4 for the unit cell; a = 7.7856(16) Å, b = 9.967(2)
Å, c = 20.095(4) Å, cell volume V = 1559.4(5) Å3, 2703
independent reflections and max/min residual electron den-
sity [e Å3].: 0.150/− 0.192. All non-hydrogen atoms were
refined with anisotropic displacement parameters. Hydro-
gen atoms were placed in ideal positions and refined as
riding atoms with relative isotropic displacement param-
eters. A view of the structure is depicted in Fig. 1. CCDC-
1570370 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/data_request/cif.
(E)‑2‑((E)‑4‑Chlorobenzylidene)‑6‑((E)‑3‑phenylallylidene)
cyclohexan‑1‑one (4r)
Yellow solid; mp 149–150 °C; IR (KBr): 2938, 1658,
1487 cm− 1; 1H NMR (400 MHz, CDCl3) δ 1.73–1.79 (m,
2H), 2.74–2.80 (m, 4H), 6.91–7.04 (m, 2H), 7.19–7.30 (m,
8H), 7.43 (d, J=8.0 Hz, 7.64 (s, 2H), 7.61 (d, J=8.0 Hz,
7.64 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 22.4, 26.6,
28.3, 123.5, 127.2, 128.6, 128.8, 129.0, 131.5, 131.6, 134.4,
134.5, 135.0, 135.2, 136.7, 137.0, 141.2, 189.4 ppm; MS
(70 eV) m/z: 334 [M+], 258, 231, 202, 133. Anal. Calcd for
C22H19ClO: C, 78.92; H, 5.72. Found: C, 79.08; H, 5.68.
(E)‑2‑((E)‑4‑Chlorobenzylidene)‑6‑(2‑phenylpropylidene)
cyclohexan‑1‑one (4s)
Yellow oil; IR (KBr): 2929, 1673, 1617, 1490 cm−1; 1H NMR
(250 MHz, CDCl3) δ 1.4 (d, J=7.0 Hz, 3H), 1.78–1.80 (m,
2H), 2.64–2.83 (m, 4H), 3.79 (q, J=7.0 Hz, 1H), 7.07–7.70
(m, 11H); 13C NMR (63 MHz, CDCl3) δ 21.7, 22.5, 26.3,
28.4, 38.3, 126.5, 127.1, 128.6, 128.7, 130.9, 131.6, 134.3,
134.4, 135.2, 136.7, 144.6, 144.8, 189.7 ppm; MS (70 eV)
m/z 336 [M+], 322, 231, 183; Anal. Calcd for C22H21ClO: C,
78.44; H, 6.28. Found: C, 78.31; H, 6.22.
(E)‑2‑((E)‑4‑Methylbenzylidene)‑6‑(naphthalen‑2‑ylmethyl‑
ene)cyclohexan‑1‑one (4t)
Yellow solid; mp 122–124 °C; IR (KBr) 2930, 1661,
1563 cm− 1; 1H NMR (500 MHz, CDCl3) δ 1.79–1.84 (m,
2H), 2.40 (s, 3H), 2.95–2.98 (m, 2H), 3.00–3.04 (m, 2H),
7.23 (d, J = 8.0 Hz, 2H), 7.26 (s, 1H), 7.41 (d, J = 8.0 Hz,
2H), 7.49–7.53 (m, 2H), 7.57–7.59 (m, 1H), 7.83–7.88 (m,
3H), 7.94–7.97 (m, 2H); 13C NMR (125 MHz, CDCl3) δ
21.5, 23.1, 28.6, 28.7, 126.4, 126.9, 127.6, 127.7, 127.9,
Fig. 1 X-ray crystal structure of compound 4k (thermal ellipsoids set
at the 40% probability level). Selected bond lengths [Å] and angles
[°]: C9-O1 1.248(4), C13-N1 1.468(4), C12-N1 1.463(4), C15-O2
1.388(4), C18 C15 O2 110.9(4), O1 C9 C8 121.2(4)
1 3

Journal of the Iranian Chemical Society
Table 1 Optimization of
the process for competitive
synthesis of 3a, 4a, and 5a
Entry
Conditions
Yieldb 3a (%)
Yieldb 4a (%)
Yieldb 5 (%)
c
1
2
3
4
5
6
7
8
PhNH2
5>
5>
5>
30
–
–
–
–
–
–
–
20
40
50
60
65
80
72
5>
5>
5>
5>
5>
–
Piperidinec
Morpholinec
Et2NHc
Pyrrolidine c
90
Pyrrolidinec,d
5>
5>
5>
5>
5>
5>
5>
5>
5>
NaOH/H2Oc
92
(i) pyrrolidine.c (ii) Ca(OH)2/H2Oe
(i) pyrrolidine.c (ii) KOH/H2Oe
(i) pyrrolidine.c (ii) NaOH/H2Oe
(i) pyrrolidine.c (ii) NaOH/EtOHe
(i) pyrrolidine.c (ii) NaOH/H2O/EtOHe
(i) pyrrolidine.c (ii) NaOH/H2O/MeOHe
(i) pyrrolidine.c (ii) NaOH/H2O/MeOHe,f
5>
5>
5>
5>
5>
5>
18>
9
10
11
12
13
14
aReactions were conducted under ultrasound irradiation
bGC yields
c1a:PhCHO:base=1.0:1.0: 0.75; 30 min
dSilent conditions
eHydroxide (10 mol% in MeOH/H2O), 4-ClC6H4CHO (1.0 equiv), 2 min
f4-ClC6H4CHO is used in the 1st step and PhCHO is used in the 2nd step
Results and discussion
First, we optimized the process to facilitate selective syn-
thesis of 3a (R=Ph, X=NMe) or 4a (R=Ph, R′=ClC6H4,
X=NMe) by conducting the reaction of 1-methylpiperidin-
4-one 1a with PhCHO and 4-ClC6H4CHO (Table 1). In the
presence of aniline, piperidine, or morpholine no detectable
amount of 3a was formed for the reaction with the first alde-
hyde (entries 1–3), while Et2NH caused 30% formation of 3a
(entry 4). The outcome improved substantially when pyrroli-
dine was used (entry 5), while the same mixture almost gave
no product under silent conditions (entry 6). The process
mainly led to the synthesis of 5 (R=Ph, X=NMe) in aqueous
NaOH medium (entry 7). Thus, pyrrolidine was chosen as the
optimum reagent for the first C=C bond formation. When
various basic conditions were used to obtain 4a (entries
8–13), aqueous NaOH in MeOH resulted the best outcome.
Importantly, when 4-ClC6H4CHO was used in the first con-
densation instead of PhCHO, yield of 4a was decreased and
instead more 5 was formed (entry 14). This suggested that
the more electron-donating aldehyde is better to be used first.
The observation would be attributed to less acidity of the
α-hydrogens of the respective monoarylidene intermediate
due to having richer electronic nature which allows selective
deprotonation of the remaining starting ketone as opposed to
competitive formation of symmetrical bisarylidenes.
Table 2 Synthesis of various derivatives of 4 starting from 1a
Entry
Product
R
R′
Time
(min)/
yielda (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
C6H5
C6H5
C6H5
4-ClC6H4
4-O2NC6H4
4-FC6H4
C6H5
32/80
33/77
31/75
31/77
33/68
33/65
35/77
34/79
35/78
34/68
31/70
33/70
31/75
CH=CHC6H5
4-MeOC6H4
4-ClC6H4
2-FC6H4
4-O2NC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-FC6H4
C6H5
4-BrC6H4
4-ClC6H4
4-ClC6H4
CH=CHC6H5
4-MeOC6H4
2- furyl
4g
4h
4i
9
10
11
12
13
4j
4k
4l
2- thienyl
4-MeC6H4
Next, the optimum conditions were applied to evalu-
ate the diversity of the process by using different pairs of
aldehydes (Table 2). Thus, in the first step of each of the
4m
aIsolated yields
1 3

Journal of the Iranian Chemical Society
syntheses, the more electron-donating aldehyde was used
first and when TLC monitoring showed optimum formation
of the monoarylidene intermediate, the second aldehyde was
added along with the addition of aqueous NaOH/MeOH.
To further show the diverse scope of the reaction, we
used cyclohexanone 1b as the starting ketone (Table 3).
Therefore, products 4n–4t were obtained in high yields in
relatively longer reaction times, perhaps due to less stability
of the corresponding enolate. Similarly, the more electron-
donating aldehydes were used first so that higher yields of
the target products would be obtained.
The structure of the products was elucidated based on their
spectroscopic data. In 1H NMR spectra, the two vinylic “=CH”
protons which are chemically equivalent in symmetrical deriv-
atives separate into two different singlet signals. Similarly,
the “XCH2” groups which appear as singlets in symmetrical
derivatives, split into separate multiplets. The same dissym-
metrization occurs in the corresponding signals in 13C NMR
spectra. To confirm the suggested structures, a single crystal
of 4k was prepared and X-ray crystallography confirmed the
structure and the stereochemistry of the product (Fig. 1).
As explained above, due to the mild conditions employed
for the first condensation, there is a chance to also successfully
synthesize the monoarylidene counterparts. Thus, when we
stopped the reactions midway, both ketones 1a-b were amena-
ble to the conditions and monoarylidenes 3a–i were obtained
in good yields within 7–60 min time intervals (Table 4).
Based on these observations, a mechanism for the reaction is
proposed (Fig. 2). The better results obtained with pyrrolidine
suggest that the process goes through an iminium formation
step, which is a preferred mode of activation and can facilitate
the reaction to get the respective intermediate [49]. The sec-
ond condensation provides the final product in each reaction.
Table 3 Synthesis of various derivatives of 4 starting from 1b
Entry Product
R
R′
Time
(min)/
yielda (%)
1
2
3
4
5
6
7
4n
4o
4p
4q
4r
4s
4t
2,4-(MeO)2C6H3 4-ClC6H4
90/70
85/86
4-MeC6H4
4-MeC6H4
4-ClC6H4
2,4-Cl2C6H3
CH=CHC6H5 90/75
2,4-Cl2C6H3
4-ClC6H4
4-ClC6H4
2-naphthyl
85/75
85/78
100/57
90/80
CH=CHC6H5
C6H5CHMe
4-MeC6H4
aIsolated yields
Table 4 Synthesis of derivatives of 3
Entry
Ketone
R
(X)
Product
Time (min)/yielda (%) References
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1b
1b
1b
C6H5
NMe
NMe
NMe
NMe
NMe
NMe
CH2
3a
3b
3c
3d
3e
3f
3g
3h
3i
45/94
45/90
45/75
45/80
7/93
10/89
45/80
50/73
60/65
[49]
[49]
[49]
[31]
[50]
[49]
[31]
[31]
[31]
4-O2NC6H4
4-MeC6H4
4-ClC6H4
2- furyl
2- thienyl
C6H5
4-ClC6H4
4-MeC6H4
CH2
CH2
aIsolated yields
1 3

Journal of the Iranian Chemical Society
Fig. 2 Proposed mechanism
OH
O
O
O
NaOH/H2O
MeOH, R'CHO
)))
N
H
)))
N
N
R
R
R'
Me
R
H
R
H
N
N
Me
Me
12. S.V. Sancheti, P.R. Gogate, Ultrason. Sonochem. 36, 527 (2017)
13. Y. Kimura, K. Kuboyama, T. Ougizawa, Liq. Cryst. 43, 910 (2016)
14. R. Balamurugan, P. Kannan, J. Polym. Sci., A: Polym. Chem. 46,
5760 (2008)
Conclusions
In summary, we succeeded to design a convenient proce-
dure for efficient synthesis of dissymmetric bisarylidene
derivatives of 1-methylpiperidin-4-one and cyclohexanone
under ultrasonic conditions. Compared to other available
15. Y. Zhao, W. Wang, F. Wu, Y. Zhou, N. Huang, Y. Gu, Q. Zou, W.
Yang, Org. Biomol. Chem. 9, 4168 (2011)
16. C.A. Zoto, M.G. Ucak-Astarlioglu, R.E. Connors, J. Mol. Struct.
1105, 396 (2016)
methods, the procedure gives the products of choice in
short time periods, while the yields of undesired mono
and symmetrical derivatives are minimized. Reactions
take place in one pot and the reagents are inexpensive and
commercially available. The use of this method in other
heterocyclic and homocyclic ketones is currently under
study in our laboratory.
17. Y. Liu, Y.H. Lee, Q. Zhang, Y. Cui, X.Y. Ling, J. Mater. Chem. C
4, 4312 (2016)
18. R. Nazir, F. Bourquard, E. Balčiūnas, S. Smoleń, D. Gray, N.V.
Tkachenko, M. Farsari, D.T. Gryko, ChemPhysChem 16, 682
(2015)
19. R.R. Kumar, S. Perumal, H.B. Kagan, R. Guillot, Tetrahedron 62,
12380 (2006)
20. J. Jayashankaran, R.D.R.S. Manian, R. Venkatesan, R. Raghuna-
than, Tetrahedron 61, 5595 (2005)
21. L.M. Deck, L.A. Hunsaker, T.A. Vander Jagt, L.J. Whalen, R.E.
Royer, D.L. Vander, Jagt, Eur. J. Med. Chem. 143, 854 (2018)
22. Y. Adachi, K. Kuniyoshi, H. Matsubara, J. Fluor Chem. 197, 100
(2017)
Acknowledgements We are grateful to the Research Council at
CCERCI for the financial support of this work (CCERCI-1395-109).
23. Z.G. Hu, J. Liu, P.L. Zeng, Z.B. Dong, J. Chem. Res. 55 (2004)
24. E. Rafiee, F. Rahimi, Monatsh. Chem. 144, 361 (2013)
25. S.M. Bayomi, H.A. El-Kashef, M.B. El-Ashmawy, M.N.A. Nasr,
M.A. El-Sherbeny, F.A. Badria, L.A. Abou-Zeid, M.A. Ghaly, N.I.
Abdel-Aziz, Med. Chem. Res. 22, 1147 (2013)
References
1. M.M. Mojtahedi, M.S. Abaee, in Handbook on Applications
of Ultrasound, Sonochemistry for Sustainability, ed. by D.
Chen, S.K. Sharma, A. Mudhoo (CRC Press, New York, 2012),
pp 281–321
26. M.S. Abaee, M.M. Mojtahedi, G.F. Pasha, E. Akbarzadeh, A.
Shockravi, A.W. Mesbah, W. Massa, Org. Lett. 13, 5282 (2011)
27. M.M. Mojtahedi, M.S. Abaee, M.M. Zahedi, M.R. Jalali, A.W.
Mesbah, W. Massa, R. Yaghoubi, M. Forouzani, Monatsh. Chem.
139, 917 (2008)
2. M. Lupacchini, A. Mascitti, G. Giachi, L. Tonucci, N.
d’Alessandro, J. Martinez, E. Colacino, Tetrahedron 73, 609
(2017)
28. M.S. Abaee, M.M. Mojtahedi, M.M. Zahedi, R. Sharifi, A.W.
Mesbah, W. Massa, Synth. Commun. 37, 2949 (2007)
29. M.S. Abaee, M.M. Mojtahedi, R. Sharifi, M.M. Zahedi, H.
Abbasi, K. Tabar-Heidar, J. Iran. Chem. Soc. 3, 293 (2006)
30. M.S. Abaee, M.M. Mojtahedi, V. Hamidi, A.W. Mesbah, W.
Massa, Synthesis 40, 2122 (2008)
3. Y.T. Didenko, W.B. McNamara, K.S. Suslick, J. Am. Chem. Soc.
121, 5817 (1999)
4. R.B.N. Baig, R.S. Varma, Chem. Soc. Rev. 41, 1559 (2012)
5. I. Mohammadpoor-Baltork, M. Moghadam, S. Tangestaninejad,
V. Mirkhani, K. Mohammadiannejad-Abbasabadi, M.A. Zolfigol,
J. Iran. Chem. Soc. 8, 840 (2011)
31. M.M. Mojtahedi, M.S. Abaee, M. Samianifard, A. Shamloo, M.
Padyab, A.W. Mesbah, K. Harms, Ultrason. Sonochem. 20, 924
(2013)
6. C. Zhuang, W. Zhang, C. Sheng, W. Zhang, C. Xing, Z. Miao,
Chem. Rev. 117, 7762 (2017)
32. M.S. Abaee, F. Ehteshami, S. Forghani, M.M. Mojtahedi, A. Hadi-
zadeh, J. Iran. Chem. Soc. 14, 1151 (2017)
7. Z. Karimi-Jaberi, B. Pooladian, Green Chem. Lett. Rev. 5, 187
(2012)
33. G.-Z. Ao, M.-Z. Zhou, Y.-Y. Li, S.-N. Li, H.-N. Wang, Q.-W. Wan,
H.-Q. Li, Q.-H. Hu, Bioorg. Med. Chem. 25, 166 (2017)
34. H. Zhu, T. Xu, C. Qiu, B. Wu, Y. Zhang, L. Chen, Q. Xia, C. Li,
B. Zhou, Z. Liu, G. Liang, Eur. J. Med. Chem. 121, 181 (2016)
35. C. Qiu, Y. Hu, K. Wu, K. Yang, N. Wang, Y. Ma, H. Zhu, Y.
Zhang, Y. Zhou, C. Chen, S. Li, L. Fu, X. Zhang, Z. Liu, Bioorg.
Med. Chem. Lett. 26, 5971 (2016)
8. A.K. Panda, U. Das, N. Umemura, H. Sakagami, M. Kawase, J.
Balzarini, E. De Clercq, S.G. Dimmock, P.K. Roayapalley, J.R.
Dimmock, Bioorg. Med. Chem. Lett. 27, 1611 (2017)
9. P.V. Sri Ramya, S. Angapelly, L. Guntuku, C. Singh Digwal, B.
Nagendra Babu, V.G.M. Naidu, A. Kamal, Eur. J. Med. Chem.
127, 100 (2017)
10. E. Simoni, R. Caporaso, C. Bergamini, J. Fiori, R. Fato, P. Miszta,
S. Filipek, F. Caraci, M.L. Giuffrida, V. Andrisano, A. Minarini,
M. Bartolini, M. Rosini, ACS Med. Chem. Lett. 7, 1145 (2016)
11. A. Mai, D. Cheng, M.T. Bedford, S. Valente, A. Nebbioso, A. Per-
rone, G. Brosch, G. Sbardella, F. De Bellis, M. Miceli, L. Altucci,
J. Med. Chem. 51, 2279 (2008)
36. M.F.F.M. Aluwi, K. Rullah, B.M. Yamin, S.W. Leong, M.N.A.
Bahari, S.J. Lim, S.M.M. Faudzi, J. Jalil, F. Abas, N.M. Fauzi,
N.H. Ismail, I. Jantan, K.W. Lam, Bioorg. Med. Chem. Lett. 26,
2531 (2016)
1 3

Journal of the Iranian Chemical Society
37. U. Cersosimo, A. Sgorbissa, C. Foti, S. Drioli, R. Angelica, A.
Tomasella, R. Picco, M.S. Semrau, P. Storici, F. Benedetti, F.
Berti, C. Brancolini, J. Med. Chem. 58, 1691 (2015)
44. F.H. Allen, O. Johnson, G.P. Shields, B.R. Smith, M. Towler, J.
Appl. Crystallogr. 37, 335 (2004)
45. C.F. Macrae, P.R. Edgington, P. McCabe, E. Pidcock, G.P. Shields,
R. Taylor, J. Towler, van der Streek, J. Appl. Crystallogr. 39, 453
(2006)
38. S.Z. Vatsadze, A.G. Golikov, A.P. Kriven’ko, N.V. Zyk, Russ.
Chem. Rev. 77, 661 (2008)
39. C.A. Zoto, R.E. Connors, J. Mol. Struct. 982, 121 (2010)
40. J. Pan, T. Xu, F. Xu, Y. Zhang, Z. Liu, W. Chen, W. Fu, Y. Dai, Y.
Zhao, J. Feng, G. Liang, Eur. J. Med. Chem. 125, 478 (2017)
41. Y. Matvieiev, I. Karpenko, A. Kulinich, A. Ryabitskii, V. Pivo-
varenko, S. Shishkina, O. Shishkin, V. Kalchenko, Tetrahedron
lett. 52, 3922 (2011)
46. M.N. Burnett, C.K. Johnson, O.R.T.E.P.-I.I.I. Report, ORNL-6895
(Oak Ridge National Laboratory, Tennessee, 1996)
47. G.M. Sheldrick, Acta Crystallogr. Sect. A 64, 112 (2008)
48. P. Coppens, L. Leiserowitz, D. Rabinovich, Acta Crystallogr. 18,
1035 (1965)
49. X. Gu, X. Wang, F. Wang, H. Sun, J. Liu, Y. Xie, M. Xiang, Mol-
ecules 19, 1976 (2014)
42. M. Nakhjiri, M. Safavi, E. Alipour, S. Emami, A.F. Atash, M.
Jafari-Zavareh, S.K. Ardestani, M. Khoshneviszadeh, A. Forou-
madi, A. Shafiee, Eur. J. Med. Chem. 50, 113 (2012)
50. M.M. Mojtahedi, M.S. Abaee, M. Samianifard, A. Shamloo, Sci
Iran 21, 719 (2014)
43. L.J.J. Farrugia, Appl. Crystallogr. 32, 837 (1999)
1 3