Synthesis and Antimicrobial Evaluations of New 5-aryl Linked Bispyrazolines

Article abstract of DOI:10.1002/jhet.2583

Syntheses of new bispyrazolines 4a, 4b, 4c, 4d, 4e, 4f, 4g built around the aliphatic linkers of varying lengths have been described. The intermediate bischalcones and final bishetrocyclics were also evaluated for their antimicrobial activities.

Full text of DOI:10.1002/jhet.2583

Month 2015
Synthesis and Antimicrobial Evaluations of New 5-aryl
Linked Bispyrazolines
*
Mohamad Yusuf and Manvinder Kaur
Department of Chemistry, Punjabi University, Patiala 147002, Punjab, India
*
E-mail: yusuf_sah04@yahoo.co.in
Additional Supporting Information may be found in the online version of this article.
Received August 13, 2015
DOI 10.1002/jhet.2583
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
Syntheses of new bispyrazolines 4(a–g) built around the aliphatic linkers of varying lengths have
been described. The intermediate bischalcones and final bishetrocyclics were also evaluated for their
antimicrobial activities.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
formation of some worthwhile biologically significant deriv-
atives. Bispyrazolines are the molecules which are formed
by linking two pyrazoline moieties together through the
carbon chain of varying lengths. In view of these observations
and in continuation of our research program on the
synthesis of five membered bisheterocyclics [24–28],
we report herein the syntheses of new symmetrical
bispyrazolines 4(a–g) built around the aliphatic linkers,
which have been found to possess an interesting profile
of antimicrobial properties.
The treatment of infectious diseases still remains an
important and challenging problem. The search of novel
antimicrobial agents is a field of current and growing inter-
est. Many compounds have been synthesized with this aim,
and their clinical applications have been limited by their
relatively high risk of toxicity, bacterial resistance, and
pharmacokinetic deficiencies. Development of new antimi-
crobial products with novel structures and mode of action
remains the primary goal of scientists for the solution of
increasing bacterial resistance gained by microorganism
to classical antimicrobial agents [1]. Chalcones and their
derivatives are an attractive molecular scaffold for the search
of new biologically significant molecules [2–4], and the stud-
ies have revealed that pyrazolines have been the subject of the
major attraction for the organic chemists because they are
known to possess analgesic, antipyretic, antidepressant, tran-
quilizing, muscle relaxant, psycho analeptic, anti-convulsant,
hypotensive [5–11], monoamine oxidase inhibitor [12,13],
anti-cancer [14,15] and antimicrobial activities [16]. The
pyrazoline derivatives are also found to exhibit potent anti-
inflammatory activities [17–19]. Several pharmaceutical
drugs including celecoxib [20] and rimonabant [21] contain
the pyrazole as their core molecular entity [22,23]. Keeping
in view these potential biological applications of chalcones
and pyrazolines, it was perceived that the presence of two
pyrazoline moieties in a single molecule might result in the
RESULTS AND DISCUSSION
Earlier, we have reported the synthesis of 5-aryl and 3-aryl
linked bispyrazolines starting from 4-hydroxybenzaldehyde
[29,30], but the present bispyrazolines 4(a–g) were synthe-
sized starting from the base catalyzed Claisen–Schmidt
reaction of acetophenone with m-hydroxybenzaldehyde to
give chalcone 2, which undergoes O-alkylation reactions with
various dibromoalkanes in presence of anhydrous K2CO3,
dry acetone, and PTC (tetrabutyl ammonium iodide)
medium to yield new bischalcones 3(a–g).
In the earlier reported work [29,30], the preparations
of bischalcones required continuously heating for at
least in 6–8h, but in the present compounds 3(a–g) have
been realized by stirring at room temperature just for 1 to
1.5 h. These intermediates were refluxed with phenyl
© 2015 HeteroCorporation

M. Yusuf and M. Kaui
Vol 000
hydrazine in the presence of ethanolic NaOH for 4 h.
After completion of reactions, the solvent was distilled
under reduced pressure, and the resulting masses were
poured into ice to provide the crude products, which were
crystallized from MeOH to yield pure bispyrazolines 4(a–g)
(Scheme 1).
signals in these compounds were found to be placed at
δ 190.62–190.58 (C = O), 144.93–144.74 (C-3), and
121.23–121.01 (C-2).
1
The major feature of H-NMR spectra of 4(a–g) was
the signals of the pyrazoline ring protons (H-X, H-M,
and H-A), which were centered at δ 5.43–5.16 (dd),
3.96–3.71 (dd), and 3.11–3.08 (dd), respectively. The
vicinal coupling constant (3J) between H-X and H-M
was found to be 12.5–11.8 Hz, which reflects that these
hydrogens are cis to each other while coupling value of
JXA = 7.5–6.1 Hz and JMA = 17.4–17.0 Hz describes the
trans relationship between H-X and H-A, and H-M
and H-A are geminally placed at C-4 position of
pyrazoline ring.
The structures of the intermediates and final com-
pounds were fully determined on the basis of their spec-
troscopic data such as IR, 1H-NMR, 13C-NMR, and
ESI-MS.
IR spectra of bischalcones 3(a–g) exhibited carbonyl
group absorptions in the region at 1661–1660cmÀ1, and
bands present in the region at 1595À1573 cmÀ1 could be
ascribed to C =C stretching. The other significant bands
were found in the region at 2960–2853 (methylene C-H),
13C-NMR (100 MHz, CDCl3) data of 4(a–g) provided
enough evidence in favor of the proposed expression
where C-3‴ was resonating at δ 159.90–158.96 because
of its direct bonding to the oxygen atom. The pyrazoline
ring carbon atoms C-3, C-5, and C-4 appeared at δ 144.39–
144.26, 66.95–63.19, and 42.94–42.87, respectively.
1255–1236 and 1018–1016 (C-O) cmÀ1
. In their
1H-NMR spectra, two broad doublets resonating at δ
7.79–7.76 and 7.60–7.52 could be assigned to H-3 and
H-2, respectively. The coupling value of 16–15 Hz
between these hydrogens describes the trans geometry
around the C-2 and C-3 double bond. The doublets in
the range of δ 8.02–8.01 may be allotted to aromatic
protons H-2′, 6′. The OCH2 protons of the internal
spacer were placed at δ 4.25–3.99, and the remaining
methylene groups of the flexible chain exhibited signals
of appropriate multiplicities.
ANTIMICROBIAL ACTIVITY
The synthesized compounds 3(a–g) and 4(a–g) were
screened for their in vitro antibacterial and antifungal
activity against seven bacterial and five fungal species,
namely, Klebsiella pneumoniae (MTCC 3384), Pseudo-
monas aeruginosa (MTCC 424), Escherichia coli
(MTCC 443), Staphylococcus aureus (MTCC 96),
In the 13C-NMR spectra of 3(a–g), the internal meth-
ylene groups were resonating at δ 68.12–64.43 (OCH2);
the downfield resonance suggests their placement near
an electronegative oxygen atom. Other noticeable
Scheme 1. Synthesis of new aliphatic chain linked bispyrazolines.
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Synthesis and Antimicrobial Evaluations of New 5-aryl Linked Bispyrazolines
Bacillus subtilis (MTCC 441), Pseudomonas fluorescens
(MTCC 103), Streptococcus pyogenes (MTCC 442),
Aspergillus janus (MTCC 2751), Penicillium glabrum
(MTCC 4951), Fusarium oxysporum (MTCC 2480),
Aspergillus sclerotiorum (MTCC 1008), and Aspergillus
niger (MTCC 281), respectively. Minimum inhibitory
concentrations (MICs) were determined by using serial
dilution technique. Amoxicillin and fluconazole were
used as the standard drug as positive control while the
DMSO was used as negative control. The MIC (μg/mL)
was determined by using different dilutions of the
concerned compound. The lowest concentration required
to arrest the growth of bacterial and fungal strains was
regarded as MIC.
The results were compared with positive controls;
the standard drug amoxicillin and fluconazole. Serial
dilution of the test compounds previously dissolved
in DMSO was prepared to final concentrations of
128, 64, 32, 16, 8, 4 2 and 1 μg/mL. All the bacteria
strains were grown at 37°C for 24 h in a nutrient broth,
and fungi were grown in malt extract at 28°C for 72 h.
Each test compound was dissolved in DMSO, and MIC
thus obtained was compared with control. The suscep-
tibility of the bacteria and fungi to the test compounds
was determined by the appearance of turbidity after the
previous said time period.
The results of MIC (μg/mL) against these microbial
strains were summarized in Table 1. It is evident from
Table 1 that the 3b compound was active against E. coli
and A. sclerotiorum, while compound 3c showed signif-
icant biological activity against the fungal strains,
namely, E. coli, B. subtilis, A. janus, P. glabrum, F.
oxysporum (MIC-8 μg/mL), and A. niger (MIC-4 μg/
mL). 3e compound possesses significant activity against
S. aureus, S. pyogenes, and A. janus at MIC-8 μg/mL.
The compound 3f displayed significant activity against
E. coli, P. aeruginosa (bacteria strain), and P. glabrum
(fungi strain). The compound 3g exhibited most potent
results (MIC-8–4 μg/mL) against Klebsiella pneumonia,
B. subtilis, P. fluorescens, P. glabrum, and F. oxysporum.
The antimicrobial evaluation data revealed that
compounds containing pyrazoline moiety were possessing
admirable activity in comparison with their intermediate
compounds 3(a–g). 4g was found to be very active
(MIC-8 μg/mL) against bacterial and fungal strains E.
coli, K. pneumonia, P. aeruginosa, S. aureus, A. janus,
P. glabrum, A. niger, A. sclerotiorum, and F. oxysporum,
respectively. The compound 4f also seems to be active
against bacterial strains E. coli, P. fluorescens, S. pyogenes
and fungal strains P. glabrum, A. sclerotiorum, F. oxysporum,
respectively. The compounds 4d and 4e were found to
possess potent activity against K.pneumonia, B. subtilis, A.
janus, K. pneumonia, P. fluorescens, B. subtilis, A. niger, and
Journal of Heterocyclic Chemistry
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M. Yusuf and M. Kaui
Vol 000
A. sclerotiorum, respectively, with MIC-8–4μg/mL. Also, 4c
exhibited significant activity against E. coli, P. glabrum, and
A. sclerotiorum strain. Further, 4a and 4b were found to possess
activity against P. aeruginosa and A. niger with MIC-8μg/mL.
resulting mass was poured into iced-HCl to provide a crude
material, which was filtered off, washed with water, dried, and
crystallized from CH3OH to yield a pure yellow compound 2.
2: Yellow, yield 82%; mp 146–148°C; IR (KBr): υmax
1
cmÀ1: 3461 (OH), 1695 (C =O), 1604 (C = C); H NMR
(400 MHz, CDCl3): δ 9.12 (1H, s, OH), 8.06 (2H, d,
Jo = 7.4 Hz, H-2′, 6′), 7.78 (1H, d, Jtrans = 15.5Hz, H-3),
7.68 (2H, d, J = 6.9 Hz, H-3′, 5′), 7.51 (1H, d,
Jtrans = 15.5Hz, H-2), 7.25 (1H, t, Jo =7.6 Hz, H-4′), 7.20
(1H, d, Jo =7.6Hz, H-6″), 7.17 (1H, brs, H-2″), 7.02 (1H, t,
Jo =7.5Hz, H-5″), 6.88 (1H, dd, Jm,o =1.7, 6.9Hz, H-4″);
13C-NMR (100MHz, CDCl3): δ 189.19 (C=O), 157.65
(C-3″), 144.27 (C-3), 137.61 (C-1′), 135.64 (C-1″), 132.60
(C-2′, 6′), 129.57 (C-4′), 128.40 (C-3′, 5′), 128.18 (C-6″),
121.54 (C-5″), 119.51 (C-2), 117.73 (C-4″), 114.86 (C-2″);
ESI-MS: m/z 225 (M+1, 80%), 208 (12%), 207 (81%),
179 (54%), 178 (10%), 147 (5%); Anal. Calcd for
C15H12O2: C-80.35, H-5.35; Found: C-80.39, H-5.31%.
Synthesis of (2E,2′E)-3,3′-(propane-1,3-diylbis(oxy))bis(3,1-
phenylene))bis(1-phenylprop-2-ene-1-one) (3a). A suspension
of chalcone 2 (2.24g, 0.01mol), K2CO3 (2.0g, mol), 1,3-
dibromopropane (1.01g, 0.005mol), and tetrabutyl
ammonium iodide (1.0g) in dry acetone (25.0ml) was
stirred for 1.0h at room temperature. The progress of
reaction was monitored by TLC (Hexane-Ethylacetate:
7:3). After the completion of reaction, the reaction mixture
turned into a colorless mass, which was poured over iced-
HCl to provide a crude solid, which was recrystallized
from CH3OH:CHCl3 (3:1) to yield a pure compound 3a.
CONCLUSION
It may be concluded that readily synthesized starting
materials, available reagents along with short reaction time,
simple work-up, and isolation of the products under simple
conditions make the current method a feasible and attrac-
tive protocol for generation of series of new bispyrazoline
derivatives in good yields. Further, in vitro antibacterial
and antifungal evaluations of compounds has proved
them as potent antimicrobial agents. Among the studied
bisheterocycles, 4g has produced the marked enhance-
ment in the potency as an antibacterial and antifungal
agent. From the antimicrobial evaluations, it is revealed
that compounds with longer internal aliphatic chain
showed better potency against tested strains (MIC-8–4μg/
mL). Overall, it is concluded that bispyrazolines 4(a–g)
exhibited most significant antimicrobial potencies as
compared with their intermediate analogs 3(a–g) against
the tested strains.
EXPERIMENTAL
Melting points of all synthesized compounds were deter-
mined in an open capillary using digital melting point
apparatus and are uncorrected. IR spectra were recorded
as KBr disks on Perkin Elmer RXIFT Infrared spectropho-
3a: Light yellow, yield 75%; mp: 126–128°C; IR (KBr):
υmax cmÀ1: 3061 (aromatic C-H), 2941, 2883 (methylene
C-H), 1661 (C = O), 1595 (C = C), 1242, 1018 (C-O); H-
1
NMR (400MHz, CDCl3): δ 8.02 (4H, dd, J =7.1, 5.2Hz,
H-2′, 6′), 7.78 (4H, d, Jtrans = 15.6 Hz, H-3), 7.58 (6H, m,
H-2, 3′, 5′), 7.32 (2H, t, Jo = 8.4 Hz, H-4′), 7.23 (2H, t,
J = 7.3 Hz, H-5″), 7.21 (2H, d, Jo = 7.6 Hz, H-6″), 7.18
(2H, brs, H-2″), 6.98 (2H, dd, Jo,m = 7.6, 1.8 Hz, H-4″),
4.25 (4H, t, Jvic = 6.2 Hz, OCH2), 2.31 (2H, quintet,
Jvic = 6.1 Hz, OCH2CH2); 13C-NMR (100MHz, CDCl3):
δ 190.58 (C = O), 158.9 (C-3″), 144.74 (C-3), 138.15 (C-
1′), 136.30 (C-1″), 132.86 (C-2′, 6′), 130.03 (C-4′),
128.66 (C-3′, 5′), 128.54 (C-6″), 122.40 (C-5″), 121.35
(C-2), 116.82 (C-4″), 113.98 (C-2″), 64.43 (OCH2),
29.29 (OCH2CH2); ESI-MS: m/z 511 (M + Na, 29%), 489
(M + 1, 19%), 423 (6%), 360 (9%), 337 (26%), 242 (9%),
167 (10%), 146 (13%), 94 (18%); Anal. Calcd for
C33H28O4: C-81.14, H-5.73; Found: C-81.10, H-5.77%.
Synthesis of (2E,2′E)-3,3′-(butane-1,4-diylbis(oxy))bis(3,1-
phenylene))bis(1-phenylprop-2-ene-1-one) (3b). The com
pound 3b was synthesized from the reaction of chalcone 2
(2.24g, 0.01mol), 1,4-dibromobutane (1.08g, 0.005mol)
under the same conditions as described earlier for 3a.
tometer (Buckinghamshire, England) in 4000–450cmÀ1
.
Both 1H-NMR and 13C-NMR spectra of the compounds were
recorded on the Bruker Avance-II NMR spectrometer
(Fallanden, Switzerland) at 400 and 100MHz, respectively.
Chemical shifts were measured relative to internal reference
standard, Tetramethylsilane (δ =0) in CDCl3, or DMSO-d6
and were reported on δ scale (ppm). Coupling constants were
given in Hz. The mass spectra were scanned on the Waters
Micromass Q-T of Micro (ESI) spectrometer (Vernon Hills,
IL). The purity of the compounds was checked by TLC plates
coated with silica gel (suspended in chloroform-methanol,
1: 1), and iodine vapors were used as visualizing agent. The
cultures required for the biological studies of prepared com-
pounds were obtained from MTCC (Microbial Type Culture
Collection & Gene Bank, Chandigarh-160036, India).
Synthesis of (E)-3-(3-hydroxyphenyl)-1-phenylprop-2-en-1-
one (2). A mixture of acetophenone (5.0 g, 0.0042mol),
3-hydroxy-benzaldehyde 1 (5.0g, 0.0042mol), and NaOH
(5.0g, 0.024mol) in EtOH (25.0mL) was stirred for 10h
at 0°C. During the course of reaction, the initially formed
creamish mixture changed to a reddish gummy mass. The
3b: Yellow, yield 72%; mp: 118–120°C; IR (KBr): υmax
cmÀ1: 3061 (aromatic C-H), 2943, 2874 (methylene C-H),
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Synthesis and Antimicrobial Evaluations of New 5-aryl Linked Bispyrazolines
1
1661 (C =O), 1595 (C = C), 1253, 1018 (C-O); H-NMR
(400 MHz, CDCl3): δ 8.01 (4H, dd, J = 7.3, 5.4 Hz, H-2′,
6′), 7.76 (4H, d, Jtrans = 15.5 Hz, H-3), 7.58 (6H, m, H-2,
3′, 5′), 7.33 (2H, t, Jo =8.0 Hz, H-4′), 7.24 (2H, t, J = 7.1,
4.5Hz, H-5″), 7.20 (2H, d, Jo =7.3Hz, H-6″), 7.16 (2H, brs,
H-2″), 6.97 (2H, dd, Jo,m = 7.2, 1.9Hz, H-4″), 4.21 (4H, t,
Jvic =6.2Hz, OCH2), 2.14 (2H, quintet, Jvic =6.1Hz,
OCH2CH2); 13C-NMR (100MHz, CDCl3): δ 190.58
(C= O), 158.91 (C-3″), 144.74 (C-3), 138.15 (C-1′), 136.30
(C-1″), 132.86 (C-2′, 6′), 130.03 (C-4′), 128.66 (C-3′, 5′),
128.54 (C-6″), 122.40 (C-5″), 121.15 (C-2), 116.82 (C-4″),
113.98 (C-2″), 64.43 (OCH2), 29.29 (OCH2CH2); ESI-MS:
m/z 525 (M+ Na, 23%), 503 (M +1, 16%), 485 (6%), 360
(5%), 338 (24%), 242 (5%), 167 (8%), 146 (7%), 94 (8%);
Anal. Calcd for C34H30O4: C-81.27, H-5.97; Found:
C-81.32, H-5.93%.
4.05 (4H, t, Jvic =6.3Hz, OCH2), 1.86 (4H, t, Jvic =6.4Hz,
OCH2CH2), 1.58 (4H, quintet, Jvic =7.1Hz, OCH2CH2CH2);
13C-NMR (100 MHz, CDCl3): δ 190.61 (C = O), 159.46
(C-3″), 144.88 (C-3), 138.19 (C-1′), 136.23 (C-1″), 132.85
(C-2′, 6′), 129.94 (C-4′), 128.66 (C-3′, 5′), 128.54 (C-6″),
122.30 (C-5″), 121.08 (C-2), 116.80 (C-4″), 114.04 (C-2″),
67.94 (OCH2), 29.22 (OCH2CH2), 25.91 (OCH2CH2CH2);
ESI-MS: m/z 541 (M+1, 19%), 458 (17%), 437 (8%), 360
(17%), 339 (28%), 338 (100%), 283 (15%), 202 (21%),
167 (11%), 146 (8%), 94 (9%); Anal. Calcd for C36H34O4:
C-81.50, H-6.41; Found: C-81.54, H-6.45%.
Synthesis of (2E,2′E)-3,3′-(octane-1,8-diylbis(oxy))bis(3,1-
phenylene))bis(1-phenylprop-2-ene-1-one) (3e). The compound
3e was synthesized from the reaction of chalcone 2 (2.24g,
0.01mol) with 1,8-dibromooctane (1.36g, 0.005mol) under
the same conditions as described previously for 3a.
Synthesis of (2E,2′E)-3,3′-(pentane-1,5-diylbis(oxy))bis(3,1-
phenylene))bis(1-phenylprop-2-ene-1-one) (3c). The com
pound 3c was prepared from the reaction of chalcone
2 (2.24g, 0.01mol), 1,5-dibromopentane (1.14g, 0.005mol)
under the same conditions as used earlier for 3a.
3e: Cream, yield 73%; mp: 114–116°C; IR (KBr):
υ
max cmÀ1: 3055 (aromatic C-H), 2920, 2894 (methylene
C-H), 1660 (C = O), 1578 (C = C), 1251, 1017 (C-O); 1H-
NMR (400 MHz, CDCl3): δ 8.02 (4H, d, Jo = 7.1 Hz, H-
2′, 6′), 7.79 (4H, d, Jtrans = 15.6 Hz, H-3), 7.50 (6H, m,
Jo = 7.6 Hz, H-2, 3′, 5′), 7.32 (2H, t, Jo = 7.9 Hz, H-4′),
7.26 (2H, t, Jo = 7.3 Hz, H-5″),7.20 (2H, d, Jo = 7.3 Hz,
H-6″), 7.16 (2H, brs, H-2″), 6.96 (2H, dd, Jm,o = 2.0,
8.1 Hz, H-4″), 4.02 (4H, t, Jvic = 6.2 Hz, OCH2), 1.85
(4H, t, Jvic = 6.6 Hz, OCH2CH2), 1.49 (4H, m,
OCH2CH2CH2), 1.41 (4H, m, OCH2CH2CH2CH2);
13C-NMR (100 MHz, CDCl3): δ 190.62 (C = O), 159.50
(C-3″), 144.91 (C-3), 138.20 (C-1′), 136.21 (C-1″),
132.84 (C-2′, 6′), 129.95 (C-4′), 128.66 (C-3′, 5′),
128.54 (C-6″), 122.29 (C-5″), 121.03 (C-2), 116.83 (C-4″),
114.03 (C-2″), 68.08 (OCH2), 29.34 (OCH2CH2), 29.26
(OCH2CH2CH2), 26.03(OCH2CH2CH2CH2); ESI-MS: m/z
597 (M+K, 11%), 569 (M+1, 30%), 507 (5%), 437 (6%),
425 (11%), 360 (8%), 339 (25%), 338 (100%), 303 (13%),
274 (9%), 215 (16%), 167 (22%), 151 (5%), 126 (32%),
102 (48%), 90 (25%); Anal. Calcd for C38H38O4: C-81.72,
H-6.81; Found: C-81.68, H-6.77%.
3c: Light yellow, yield 69%; mp: 130–132°C; IR (KBr):
υmax cmÀ1: 3061 (aromatic C-H), 2915, 2850 (methylene
1
C-H), 1661 (C = O), 1595 (C =C), 1255, 1018 (C-O); H-
NMR (400 MHz, CDCl3): δ 8.00 (4H, d, J =7.1 Hz, H-2′,
6′), 7.78 (4H, d, Jtrans =15.6 Hz, H-3), 7.52 (6H, m, H-2,
3′, 5′), 7.32 (2H, t, Jo =7.8 Hz, H-4′), 7.23 (2H, t,
J =7.3 Hz, H-5″), 7.21 (2H, d, Jo = 7.6 Hz, H-6″), 7.16
(2H, s, H-2″), 6.97 (2H, dd, Jo,m =8.0, 1.8 Hz, H-4″),
4.05 (4H, t, Jvic = 6.3 Hz, OCH2), 1.93 (4H, quintet,
Jvic =6.6 Hz, OCH2CH2), 1.71 (2H, m, OCH2CH2CH2);
13C-NMR (100 MHz, CDCl3): δ 190.60 (C =O), 159.42
(C-3″), 144.85 (C-3), 138.18 (C-1′), 136.25 (C-1″),
132.86 (C-2′, 6′), 129.99 (C-4′), 128.67 (C-3′, 5′),
128.54 (C-6″), 122.31 (C-5″), 121.13 (C-2), 116.81 (C-
4″), 114.04 (C-2″), 67.87 (OCH2), 29.04 (OCH2CH2),
22.81 (OCH2CH2CH2); ESI-MS: m/z 554 (M + K-1, 9%),
553 (M + K-2, 22%), 513 (11%), 458 (9%), 437 (11%),
360 (20%), 339 (24%), 338 (100%), 283 (10%), 202
(13%), 167 (7%), 146 (13%), 94 (6%); Anal. Calcd for
C35H32O4: C-81.39, H-6.20; Found: C-81.34, H-6.16%.
Synthesis of (2E,2′E)-3,3′-(decane-1,10-diylbis(oxy))bis(3,1-
phenylene))bis(1-phenylprop-2-ene-1-one) (3f). The compound
3f was obtained from the reaction of chalcone 2 (2.24 g,
0.01 mol) with 1,10-dibromodecane (1.5 g, 0.005 mol)
under the same conditions as described previously for 3a.
3f: Off white, yield 77%; mp: 110–112°C; IR (KBr): υmax
cmÀ1: 3057 (aromatic C-H), 2959, 2873 (methylene C-H),
Synthesis of (2E,2′E)-3,3′-(hexane-1,6-diylbis(oxy))bis(3,1-
phenylene))bis(1-phenylprop-2-ene-1-one) (3d). The com
pound 3d was obtained by treating chalcone 2 (2.24g,
0.01mol) with 1,6-dibromohexane (1.22g, 0.005mol)
under the same conditions as described earlier for 3a.
3d: Cream, Yield 71%; mp: 122–124°C; IR (KBr): υmax
cmÀ1: 3061 (aromatic C-H), 2933, 2853 (methylene C-H),
1
1661 (C=O), 1578 (C= C), 1244, 1017 (C-O); H-NMR
(400MHz, CDCl3): δ 8.02 (4H, d, Jo =7.3Hz, H-2′, 6′),
7.78 (4H, d, Jtrans =15.7Hz, H-3), 7.50 (6H, m, H-2, 3′, 5′),
7.32 (2H, t, Jo =7.9Hz, H-4′), 7.28 (2H, t, Jo =7.2Hz, H-
5″), 7.23 (2H, d, Jo =7.6Hz, H-6″), 7.15 (2H, s, H-2″), 6.96
(2H, dd, Jm,o = 1.5, 8.0 Hz, H-4″), 4.01 (4H, t, Jvic =6.1Hz,
OCH2), 1.80 (4H, quintet, Jvic =6.6Hz, OCH2CH2), 1.48
(4H, t, Jvic =6.3Hz, OCH2CH2CH2), 1.35 (8H, m,
OCH2CH2CH2CH2CH2); 13C-NMR (100MHz, CDCl3): δ
1
1661 (C =O), 1596 (C = C), 1236, 1018 (C-O); H-NMR
(400 MHz, CDCl3): δ 8.02 (4H, dd, J = 6.9, 8.4 Hz, H-2′,
6′), 7.78 (4H, d, Jtrans =15.7 Hz, H-3), 7.52 (6H, m, H-2,
3′, 5′), 7.32 (2H, t, Jo =7.9 Hz, H-4′), 7.25 (2H, t,
J =7.1 Hz, H-5″), 7.20 (2H, d, Jo = 7.6 Hz, H-6″), 7.16
(2H, brs, H-2″), 6.96 (2H, dd, Jm,o = 4.0, 6.1 Hz, H-4″),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Yusuf and M. Kaui
Vol 000
190.62 (C=O), 159.51 (C-3″), 144.93 (C-3), 138.20 (C-1′),
136.20 (C-1″), 132.84 (C-2′, 6′), 129.95 (C-4′), 128.66 (C-
3′, 5′), 128.54 (C-6″), 122.27 (C-5″), 121.02 (C-2), 116.83
(C-4″), 114.04 (C-2″), 68.12 (OCH2), 29.53 (OCH2CH2),
29.40 (OCH2CH2CH2), 29.27 (OCH2CH2CH2CH2), 26.01
(OCH2CH2CH2CH2CH2); ESI-MS: m/z 597 (M + 1,
26%), 609 (M + Na, 13%), 491 (10%), 443 (9%), 363
(5%), 360 (16%), 339 (19%), 338 (62%), 243 (18%),
242 (100%), 202 (9%), 146 (7%), 102 (5%), 94 (3%);
Anal. Calcd for C40H42O4: C-81.91, H-7.16; Found:
C-81.96, H-7.21%.
(6H, m, H-3′, 4′, 5′), 7.06 (2H, d, Jo =8.0Hz, H-6‴), 6.85
(4H, d, Jo =7.2Hz, H-2′, 6′), 6.82 (2H, brs, H-2‴), 6.75
(4H, t, J=6.6Hz, H-4‴, 5‴), 5.21 (2H, dd, JMX =12.1Hz,
JAX =7.5Hz, H-X), 4.02 (4H, t, Jvic =5.6Hz, OCH2), 3.71
(2H, dd, JMX =12.1Hz, JMA =17.1Hz, H-M), 3.08 (2H,
dd, JAX =7.5Hz, JAM =17.1Hz, H-A), 2.16 (2H, quintet,
Jvic =5.8Hz, OCH2CH2); 13C-NMR (100MHz, CDCl3):
159.07 (C-3‴), 147.02 (C-1′), 144.29 (C-3), 132.22 (C-1‴),
130.06 (C-1″), 128.74 (C-2″, 6″), 128.56 (C-4″), 128.42
(C-3″, 5″), 128.18 (C-6‴), 125.56 (C-3′, 5′), 118.54 (C-4′),
117.61 (C-2′, 6′), 112.95 (C-5‴), 112.88 (C-4‴), 111.91
(C-2‴), 64.43 (OCH2), 63.19 (C-5), 42.90 (C-4), 29.29
(OCH2CH2); ESI-MS: m/z 669 (M+1, 42%), 592 (12%),
475 (30%), 448 (18%), 437 (8%), 338 (36%), 321 (19%),
243 (14%), 242 (29%), 202 (18%), 167 (15%), 126 (20%),
111 (18%), 85 (23%); Anal. Calcd for C45H40N4O2:
C-80.83, H-5.98, N-8.38; Found: C-80.87, H-5.93, N-8.41%.
Synthesis of (2E,2′E)-3,3′-(dodecane-1,12-diylbis(oxy))bis(3,1-
phenylene))bis(1-phenylprop-2-ene-1-one) (3g). The compound
3g was prepared by treating chalcone 2 (2.24g, 0.01mol)
with 1,12-dibromododecane (1.64g, 0.005mol) under the
same conditions as described previously for 3a.
3g: Cream, yield 74%; mp: 102–104°C; IR (KBr): υmax
cmÀ1: 3056 (aromatic C-H), 2960, 2880 (methylene
C-H), 1662 (C = O), 1575 (C = C), 1249, 1017 (C-O);
1H-NMR (400 MHz, CDCl3): δ 8.02 (4H, d, Jo = 7.2 Hz,
H-2′, 6′), 7.78 (4H, d, Jtrans = 15.6 Hz, H-3), 7.52 (6H,
m, H-2, 3′, 5′), 7.38 (2H, t, J=6.2Hz, H-4′), 7.27 (2H, t,
Jo =7.9Hz, H-5″), 7.22 (2H, d, Jo =7.6Hz, H-6″), 7.15 (2H,
s, H-2″), 6.96 (2H, dd, Jm,o =2.0, 7.8Hz, H-4″), 3.99 (4H, t,
Jvic =6.4Hz, OCH2), 1.78 (4H, quintet, Jvic =6.5Hz,
OCH2CH2), 1.46 (4H, quintet, Jvic =6.5Hz, OCH2CH2CH2),
1.30 (12H, m, OCH2CH2CH2CH2CH2CH2); 13C-NMR
(100MHz, CDCl3): δ 190.60 (C = O), 159.51 (C-3″), 144.92
(C-3), 138.16 (C-1′), 136.19 (C-1″), 132.84 (C-2′, 6′),
129.94 (C-4′), 128.66 (C-3′, 5′), 128.54 (C-6″), 122.26 (C-
5″), 121.02 (C-2), 116.83 (C-4″), 114.04 (C-2″), 68.14
(OCH2), 29.60 (OCH2CH2), 29.35 (OCH2CH2CH2), 29.43
(OCH2CH2CH2CH2), 29.27 (OCH2CH2CH2CH2CH2),
26.07 (OCH2CH2CH2CH2CH2CH2); ESI-MS: m/z 637
(M + Na, 23%), 625 (M + 1, 16%), 491 (17%), 443
(19%), 362 (25%), 360 (6%), 339 (12%), 338 (58%),
243 (28%), 242 (100%), 202 (11%), 146 (8%), 102
(9%), 94 (5%); Anal. Calcd for C42H46O4: C-82.02,
H-7.49; Found: C-82.11, H-7.45%.
Synthesis of 1,4-bis(3-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-
5-yl)phenoxy)butane (4b). The compound 4b was prepared by
treating 1,4-bischalcone 3b (0.5g, 0.001mol) with phenyl
hydrazine (0.22g, 0.002mol) under the same conditions as
described previously for 3a.
4b: Off white, yield 66%; mp: 86–88°C; IR (KBr): υmax
cmÀ1: 3058 (aromatic C-H), 2916, 2859 (methylene C-H),
1600 (C =N), 1241, 1032 (C-O); 1H-NMR (400MHz, CDCl3):
δ 7.74 (4H, d, Jo =7.3Hz, H-2″, 6″), 7.41 (2H, t, Jo =7.8Hz,
H-4″), 7.37 (4H, d, J=6.8Hz, H-3″, 5″), 7.24 (2H, t,
Jo =7.8Hz, H-6‴), 7.16 (4H, t, Jo =7.7Hz, H-3′, 5′), 7.01
(2H, d, Jo =7.6Hz, H-2‴), 6.82 (4H, t, Jo =7.7Hz, H-2′, 6′),
6.71 (4H, t, Jo =6.9Hz, H-4‴, 5‴), 6.69 (2H, t, J=6.9Hz,
H-4′), 5.43 (2H, dd, JMX =12.5Hz, JAX = 6.3 Hz, H-X), 3.84
(6H, m, H-M & OCH2), 3.10 (2H, dd, JAX =6.3Hz,
JAM =17.3Hz, H-A), 1.84 (2H, brs, OCH2CH2); 13C-NMR
(100MHz, CDCl3): δ 159.06 (C-3‴), 146.88 (C-1′), 144.27
(C-3), 132.21 (C-1‴), 129.98 (C-1″), 128.64 (C-2″, 6″),
128.44 (C-4″), 128.40 (C-3″, 5″), 128.33 (C-3′, 5′), 125.50
(C-6‴), 118.52 (C-4′), 117.60 (C-2′, 6′), 112.98 (C-5‴),
111.88 (C-4‴), 111.76 (C-2‴), 67.13 (OCH2), 63.29 (C-5),
42.92 (C-4), 28.54 (OCH2CH2); ESI-MS: m/z 684 (M+ 2,
45%), 683 (M +1, 100%), 593 (11%), 475 (32%), 448 (13%),
437 (6%), 360 (20%), 338 (36%), 321 (9%), 274 (12%), 243
(14%), 242 (70%), 202 (15%), 167 (12%), 126 (17%), 111
(8%), 85 (43%); Anal. Calcd for C46H42N4O2: C-80.93,
H-6.15, N-8.21; Found: C-80.89, H-6.19, N-8.26%.
Synthesis of 1,3-bis(3-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-
5-yl)phenoxy)propane (4a). A mixture of compound 3a
(0.48g, 0.001mol), phenyl hydrazine (0.22g, 0.002mol),
and NaOH (0.5 g, 0.013mol) in dry EtOH (30ml) was
refluxed for 4 h. The progress of reaction was monitored by
TLC (Hexane-Ethylacetate: 9: 1). After the completion of
reaction, the reaction mixture was concentrated under
vacuum, and resulting mass was poured into ice to yield a
solid substance. The crude product thus obtained was
crystallized from MeOH to yield a pure compound 4a.
Synthesis of 1,5-bis(3-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-
5-yl)phenoxy)pentane (4c). The compound 4c was obtained
from the reaction of 1,5-bischalcone 3c (0.52g, 0.001mol)
with phenyl hydrazine (0.22g, 0.002mol) under the same
conditions as described previously for 3a.
4a: Off white, yield 63%; mp: 90–92°C; IR (KBr): υmax
cmÀ1: 3056 (aromatic C-H), 2919, 2852 (methylene C-H),
1599 (C=N), 1238, 1022 (C-O); 1H-NMR (400MHz,
CDCl3): δ 7.68 (4H, d, Jo =7.2Hz, H-2″, 6″), 7.35 (2H, t,
Jo =7.8Hz, H-4″), 7.29 (4H, d, Jo =7.1Hz, H-3″, 5″), 7.16
4c: Light yellow, yield 64%; mp: 84–86°C; IR (KBr):
υmax cmÀ1: 3056 (aromatic C-H), 2921, 2848 (methylene
C-H), 1596 (C = N), 1236, 1024 (C-O); 1H-NMR
(400 MHz, CDCl3): δ 7.72 (4H, d, Jo = 7.3 Hz, H-2″, 6″),
7.40 (2H, t, Jo =7.6 Hz, H-4″), 7.34 (4H, d, Jo =7.1 Hz,
Journal of Heterocyclic Chemistry
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Month 2015
Synthesis and Antimicrobial Evaluations of New 5-aryl Linked Bispyrazolines
H-3″, 5″), 7.23 (2H, t, Jo =7.8Hz, H-6‴), 7.14 (4H, t,
Jo =8.2Hz, H-3′, 5′), 7.02 (2H, d, Jo =7.9Hz, H-2‴), 6.85
(4H, t, Jo =7.7Hz, H-2′, 6′), 6.75 (4H, t, Jo =8.0Hz, H-4‴,
5‴), 6.68 (2H, t, Jo =7.2Hz, H-4′), 5.37 (2H, dd, JMX = 12.1Hz,
JAX = 6.6Hz, H-X), 3.88 (6H, m, H-M & OCH2), 3.09 (2H, dd,
JAX =6.6Hz, JAM =17.6Hz, H-A), 1.72 (4H, quintet,
Jvic =7.0Hz, OCH2CH2), 1.52 (2H, quintet, Jvic =6.8Hz,
OCH2CH2CH2); 13C-NMR (100MHz, CDCl3): δ 158.96
(C-3‴), 147.22 (C-1′), 144.25 (C-3), 132.21 (C-1‴), 130.18
(C-1″), 128.85 (C-2″, 6″), 128.76 (C-4″), 128.68 (C-3″, 5″),
128.62 (C-6‴), 125.65 (C-3′, 5′), 118.61 (C-4′), 117.75
(C-2′, 6′), 112.95 (C-5‴), 112.89 (C-4‴), 112.07 (C-2‴),
66.95 (OCH2), 63.08 (C-5), 42.07 (C-4), 25.29 (OCH2CH2),
22.16 (OCH2CH2CH2); ESI-MS: m/z 475 (22%), 437 (5%),
360 (24%), 338 (60%), 321 (13%), 274 (14%), 243 (78%),
242 (100%), 202 (6%), 167 (8%), 151 (7%), 126 (9%), 110
(11%), 82 (6%); Anal. Calcd for C47H44N4O2: C-81.03,
H-6.32, N-8.04; Found: C-81.07, H-6.28, N-8.06%.
CDCl3): δ 7.73 (4H, d, Jo =7.4Hz, H-2″, 6″), 7.41 (2H, t,
Jo =7.0Hz, H-4″), 7.35 (4H, d, Jo =7.1Hz, H-3″, 5″), 7.23
(2H, t, Jo =7.7Hz, H-6‴), 7.15 (4H, t, Jo =7.7Hz, H-3′,
5′), 7.01 (2H, d, Jo =8.0Hz, H-2‴), 6.82 (4H, t, Jo =8.0Hz,
H-2′, 6′), 6.72 (4H, d, Jo =7.9Hz, H-4‴, 5‴), 6.68 (2H, t,
Jo =7.2Hz, H-4′), 5.38 (2H, dd, JMX =12.2Hz, JAX =6.4Hz,
H-X), 3.88 (6H, m, H-M & OCH2), 3.09 (2H, dd,
JAX =6.4Hz, JAM =17.3Hz, H-A), 1.71 (4H, t, Jvic =6.2Hz,
OCH2CH2), 1.44 (8H, m, OCH2CH2CH2CH2); 13C-NMR
(100MHz, CDCl3): δ 159.07 (C-3‴), 147.02 (C-1′), 144.26
(C-3), 132.22 (C-1‴), 130.04 (C-1″), 128.71 (C-2″, 6″),
128.53 (C-4″), 128.48 (C-3″, 5″), 128.19 (C-6‴), 125.56
(C-3′, 5′), 118.54 (C-4′), 117.61 (C-2′, 6′), 112.95 (C-5‴),
112.88 (C-4‴), 111.91 (C-2‴), 67.24 (OCH2), 63.19 (C-5),
42.90 (C-4), 28.66 (OCH2CH2), 28.56 (OCH2CH2CH2),
25.40 (OCH2CH2CH2CH2); ESI-MS: m/z 740 (M+2, 4%),
739 (M+1, 13%), 650 (8%), 504 (7%), 475 (37%), 448
(23%), 321 (9%), 273 (12%), 209 (5%), 168 (7%), 124
(27%), 93 (30%), 80 (100%); Anal. Calcd for C50H50N4O2:
C-81.30, H-6.77, N-7.58; Found: C-81.34, H-6.73,
N-7.61%.
Synthesis of 1,6-bis(3-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-
5-yl)phenoxy)hexane (4d). The compound 4d was synthesized
from the reaction of 1,6-bischalcone 3d (0.54g, 0.001mol)
with phenyl hydrazine (0.22g, 0.002mol) under the same
conditions as described previously for 3a.
Synthesis of 1,10-bis(3-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-
5-yl)phenoxy)decane (4f). The compound 4f was prepared
from the reaction of 1,10-bischalcone 3f (0.59 g, 0.001mol)
with phenyl hydrazine (0.22g, 0.002mol) under the same
conditions as described previously for 3a.
4d: Off white, yield 69%; mp: 78–80°C; IR (KBr): υmax
cmÀ1: 3057 (aromatic C-H), 2918, 2853 (methylene C-H),
1596 (C =N), 1238, 1043 (C-O); 1H-NMR (400MHz,
CDCl3): δ 7.72 (4H, d, Jo =7.2Hz, H-2″, 6″), 7.40 (2H, t,
Jo =7.1Hz, H-4″), 7.34 (4H, d, Jo =7.2Hz, H-3″, 5″), 7.23
(2H, t, Jo =7.8Hz, H-6‴), 7.12 (4H, t, Jo =7.4Hz, H-3′,
5′), 7.02 (2H, d, Jo =7.9Hz, H-2‴), 6.85 (4H, t, Jo =7.3Hz,
H-2′, 6′), 6.75 (4H, dd, J= 8.0, 5.9 Hz, H-4‴, 5‴), 6.68
(2H, t, Jo =7.2Hz, H-4′), 5.31 (2H, dd, JMX =12.1Hz,
JAX =6.3Hz, H-X), 3.85 (6H, m, H-M & OCH2), 3.11
(2H, dd, JAX =6.3Hz, JAM =17.2Hz, H-A), 1.67 (4H, t,
Jvic =7.9Hz, OCH2CH2), 1.41 (2H, brs, OCH2CH2CH2);
13C-NMR (100MHz, CDCl3): δ 159.07 (C-3‴), 146.87
(C-1′), 144.26 (C-3), 132.20 (C-1‴), 129.98 (C-1″), 128.64
(C-2″, 6″), 128.44 (C-4″), 128.39 (C-3″, 5″), 128.18 (C-6‴),
125.50 (C-3′, 5′), 118.52 (C-4′), 117.57 (C-2′, 6′), 112.87
(C-5‴), 112.85 (C-4‴), 111.84 (C-2‴), 67.17 (OCH2), 63.28
(C-5), 42.92 (C-4), 28.54 (OCH2CH2), 25.27 (OCH2CH2CH2);
ESI-MS: m/z 711 (M + 1, 23%), 650 (8%), 647 (21%), 503
(8%), 475 (20%), 362 (24%), 338 (64%), 273 (18%), 209
(16%), 168 (7%), 156 (12%), 124 (28%), 93 (31%), 80
(13%); Anal. Calcd for C48H46N4O2: C-81.12, H-6.47,
N-7.88; Found: C-81.07, H-6.51, N-7.83%.
4f: Light yellow, yield 73%; mp: 70–72°C; IR (KBr):
υmax cmÀ1: 3059 (aromatic C-H), 2918, 2857 (methylene
C-H), 1599 (C =N), 1243, 1038 (C-O); 1H-NMR (400MHz,
CDCl3): δ 7.72 (4H, d, Jo =7.2Hz, H-2″, 6″), 7.39 (2H, t,
Jo =7.6Hz, H-4″), 7.32 (4H, d, Jo =7.2Hz, H-3″, 5″), 7.22
(2H, t, Jo =7.8Hz, H-6‴), 7.12 (4H, t, Jo =7.5Hz, H-3′, 5′),
7.02 (2H, d, Jo =7.8Hz, H-2‴), 6.82 (4H, t, Jo =7.9Hz, H-
2′, 6′), 6.77 (4H, dd, J=8.0, 6.2Hz, H-4‴, 5‴), 6.67 (2H, t,
Jo =7.2Hz, H-4′), 5.36 (2H, dd, JMX = 12.2 Hz, JAX =6.5Hz,
H-X), 3.86 (6H, m, H-M & OCH2), 3.09 (2H, dd,
JAX =6.5Hz, JAM =17.4Hz, H-A), 1.71 (4H, quintet,
Jvic =6.1Hz, OCH2CH2), 1.45 (4H, quintet, Jvic =6.0Hz,
OCH2CH2CH2CH2), 1.34 (8H, m, OCH2CH2CH2CH2CH2);
13C-NMR (100 MHz, CDCl3): δ 159.04 (C-3‴), 146.95
(C-1′), 144.28 (C-3), 132.63 (C-1‴), 130.26 (C-1″), 128.81
(C-2″, 6″), 128.69 (C-4″), 128.47 (C-3″, 5″), 128.32 (C-6‴),
125.52 (C-3′, 5′), 118.54 (C-4′), 117.61 (C-2′, 6′), 112.95
(C-5‴), 112.88 (C-4‴), 111.87 (C-2‴), 67.89 (OCH2), 64.32
(C-5), 42.94 (C-4), 29.59 (OCH2CH2), 29.38 (OCH2CH2CH2),
26.43 (OCH2CH2CH2CH2), 26.07 (OCH2CH2CH2CH2CH2);
ESI-MS: m/z 768 (M+ 2, 22%), 765 (40%), 681 (5%), 591
(6%), 539 (12%), 475 (20%), 359 (6%), 242 (17%), 209
(6%), 167 (6%), 151 (16%), 126 (19%), 110 (21%), 85
(100%); Anal. Calcd for C52H54N4O2: C-81.46, H-7.04,
N-7.31; Found: C-81.51, H-7.07, N-7.27%.
Synthesis of 1,8-bis(3-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-
5-yl)phenoxy)octane (4e). The compound 4e was prepared by
the reaction of 1,8-bischalcone 3e (0.56g, 0.001mol) with
phenyl hydrazine (0.22g, 0.002mol) under the same
conditions as described previously for 3a.
4e: Off white, yield 71%; mp: 74–76°C; IR (KBr):
Synthesis of 1,12-bis(3-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-
5-yl)phenoxy)dodecane (4g). The compound 4g was
synthesized by reacting 1,12-bischalcone 3g (0.62 g,
υ
max cmÀ1: 3055 (aromatic C-H), 2937, 2849 (methylene
C-H), 1598 (C=N), 1239, 1042 (C-O); 1H-NMR (400MHz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M. Yusuf and M. Kaui
Vol 000
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[20] Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.; Carter, J. S.;
Collins, P. W.; Docter, S.; Graneto, M. J.; Lee, L. F.; Malecha, J. W.;
Miyashiro, J. M.; Rogers, R. S.; Rogier, D. J.; Yu, S. S.; Anderson,
G. D.; Burton, E. G.; Cogburn, J. N.; Gregory, S.; Koboldt, C. M.;
Perkins, W. E.; Seibert, K.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson,
P. C. J Med Chem 1997, 40, 1347.
υ
max cmÀ1: 3056 (aromatic C-H), 2943, 2852 (methylene
C-H), 1598 (C = N), 1247, 1023 (C-O); 1H-NMR
(400MHz, CDCl3): δ 7.69 (4H, d, Jo =7.1Hz, H-2″, 6″),
7.47 (2H, t, Jo =7.7Hz, H-4″), 7.32 (4H, d, Jo =6.9Hz,
H-3″, 5″), 7.21 (2H, t, Jo =7.6Hz, H-6‴), 7.15 (4H, t, Jo =7.3Hz,
H-3′, 5′), 7.06 (2H, d, Jo = 7.6 Hz, H-2‴), 6.86 (4H, d,
Jo = 7.8Hz, H-2′, 6′), 6.74 (4H, d, J =6.8 Hz, H-4‴, 5‴),
6.67 (2H, t, Jo = 7.2 Hz, H-4′), 5.16 (2H, dd, JMX = 11.8Hz,
JAX = 7.5Hz, H-X), 3.88 (6H, m, H-M & OCH2), 3.09 (2H,
dd, JAX = 7.5Hz, JAM = 17.0Hz, H-A), 1.69 (4H, brs,
OCH2CH2), 1.26 (20H, m, OCH2CH2CH2CH2CH2CH2);
13C-NMR (100 MHz, CDCl3): δ 159.90 (C-3‴), 146.89
(C-1′), 144.39 (C-3), 132.79 (C-1‴), 130.27 (C-1″),
128.98 (C-2″, 6″), 128.66 (C-4″), 128.61(C-3″, 5″),
128.42 (C-6‴), 125.50 (C-3′, 5′), 119.20 (C-4′), 117.99
(C-2′, 6′), 113.46 (C-5‴), 112.81 (C-4‴), 112.02 (C-2‴),
68.02 (OCH2), 64.67 (C-5), 42.92 (C-4), 29.69 (OCH2CH2),
29.49 (OCH2CH2CH2), 29.34 (OCH2CH2CH2CH2), 26.12
(OCH2CH2CH2CH2CH2), 18.46 (OCH2CH2CH2CH2CH2
CH2); ESI-MS: m/z 795 (M+1, 12%), 765 (32%), 680
(15%), 575 (18%), 539 (12%), 497 (21%), 359 (8%), 242
(17%), 209 (6%), 167 (6%), 151 (16%), 126 (19%), 110
(21%), 85 (13%); Anal. Calcd for C54H58N4O2: C-81.61,
H-7.30, N-7.05; Found: C-81.57, H-7.34, N-7.09%.
[21] Deng, X.; Mani, N. S. Org Lett 2008, 10, 1307.
[22] Katritzky, A. R.; Wang, M.; Zhang, S.; Voronkov, M. V. J Org
Chem 2001, 66, 6787.
[23] Deng, X.; Mani, N. S. Org Lett 2006, 8, 3505.
[24] Yusuf, M.; Jain, P. Arab J Chem 2014, 9, 525.
[25] Yusuf, M.; Jain, P. Spectrochim Acta A Mol Biomol Spectrosc
2012, 96, 295.
Acknowledgement. Authors are highly thankful to UGC, New Delhi
for providing MANF-SRF as the financial support for this
research work.
[26] Yusuf, M.; Jain, P. J Chem Sci 2013, 125, 117.
[27] Yusuf, M.; Kaur, M.; Jain, P.; Solanki, I. Spectrochim Acta A
Mol Biomol Spectrosc 2012, 97, 470.
REFERENCES AND NOTES
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet