Syntheses and biological activity of chalcones-imidazole derivatives

Article abstract of DOI:10.1007/s11164-012-0665-z

A number of novel 13-membered chalcone-imidazole derivatives were prepared and have been synthesized and characterized by IR, ¹H NMR, ¹³C NMR and elemental analysis, the results conformed well to expected structures. Substituted acetophenones and benzaldehydes were condensed using the Claisen-Schmidt base-catalyzed aldol condensation. Methyl on the aromatic ring of chalcones was brominated by NBS, and then the resulting mixture was reacted with imidazole to get the target compound. Several chalcones showed in vitro antibacterial activity against Gram-bacterial. The results showed that these are potential antibacterial compounds.

Full text of DOI:10.1007/s11164-012-0665-z

Res Chem Intermed (2013) 39:1037–1048
DOI 10.1007/s11164-012-0665-z
Syntheses and biological activity of chalcones-imidazole
derivatives
•
•
•
Yu-Ting Liu Xiao-Ming Sun Da-Wei Yin
Fang Yuan
Received: 17 December 2011 / Accepted: 26 May 2012 / Published online: 21 June 2012
Ó Springer Science+Business Media B.V. 2012
Abstract A number of novel 13-membered chalcone-imidazole derivatives were
1
prepared and have been synthesized and characterized by IR, H NMR, 13C NMR
and elemental analysis, the results conformed well to expected structures. Substi-
tuted acetophenones and benzaldehydes were condensed using the Claisen–Schmidt
base-catalyzed aldol condensation. Methyl on the aromatic ring of chalcones was
brominated by NBS, and then the resulting mixture was reacted with imidazole to
get the target compound. Several chalcones showed in vitro antibacterial activity
against Gram-bacterial. The results showed that these are potential antibacterial
compounds.
Keywords Chalcone ꢀ Imidazole ꢀ Antibacterial activity ꢀ Claisen–Schmidt
Introduction
Imidazole and its derivatives are of great significance due to their important roles in
biological systems, particularly in enzymes, as proton donors and/or acceptors,
coordination system ligands, and the base of charge–transfer processes [1, 2].
Unlike pyrrole (a proton donor) and pyridine (a proton acceptor), 1H-imidazole has
both proton donor and acceptor properties [3, 4]. Imidazole functionalities have
been used for complex reactions with different molecular components such as
carboxylic acids to obtain liquid crystalline assemblies [5]. The imidazole nucleus
appears in a number of naturally occurring products like the amino acids histidine
and purines, which comprise many of the most important bases in nucleic acids.
Imidazole derivatives possess a broad spectrum of pharmacological activities such
Y.-T. Liu (&) ꢀ X.-M. Sun ꢀ D.-W. Yin ꢀ F. Yuan
Key Laboratory of Auxiliary Chemistry and Technology for Chemical Industry, Ministry
of Education, Shaanxi University of Science and Technology, Xi’an 710021, China
e-mail: ziyounvshenyadianna@126.com
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Y.-T. Liu et al.
as anticonvulsant [6], anti-Parkinson [7] and mono-aminooxidase (MAO) inhibitory
[8] activity. Chalcones are known to exhibit various biological activities, such as
antioxidant [9], antiinflammatory [10], antimalarial [11], antileishmanial [12],
anticancer [13], and antitumor [14]. In addition, chalcones are very important
compounds as intermediates in organic syntheses, Their synthesis, characterization,
spectroscopic properties, and reactivity have been the subject of many papers
[15–21]. On the basis of these observations, and as part of our program in the search
for new antibacterial and antifungal bioorganometallics, we have designed and
synthesized a number of novel chalcone-imidazole derivatives and evaluated their
antimicrobial activity.
Experimental
Chemistry
All chemicals were commercially availabled, all the solvents were dried before use
by the literature methods [22], and moisture was excluded from the glass apparatus
using CaCl2 drying tubes. The melting points were determined in an open glass
capillary and were uncorrected. C, H, and N analyses were performed with a Fisons
EA 1108 (CHNS-O) elemental analyzer. IR spectra were recorded on a Nicolet
FT-IR-170SX instrument (KBr discs) in the 4,000–400 cm-1 region. NMR spectra
were recorded on a Varian Gemini 400 spectrometer, using DMSO-d6 as the solvent
and TMS as the internal standard. Chemical shifts are expressed in ppm.
Prepared chalcone 3a–3m
The chalcones (3a–3m) were synthesized by a base-catalyzed Claisen–Schmidt
condensation reaction21 of substituted acetophenones and aldehydes (Scheme 1).
The parallel synthesis was carried out in an Advanced ChemTech Instrument model
Vantage. In most cases, the starting materials were commercially available. An
EtOH solution of substituted acetophenones (1a–e) (1.0 equiv) and aldehydes (2a–j)
(1.0 equiv) was added with 50 % KOH (2.5 equiv). The reaction mixture was stirred
overnight at room temperature; the pH was adjusted to 3–4 with aq 2 M HCl
solution; the precipitate was collected by filtration and purified by recrystallization
in EtOH [23].
Scheme 1 Synthetic of route for chalcone 3a–m
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Syntheses and biological activity
1039
Prepared chalcones-imidazole derivatives 5a–5m
Five mmol substituted chalcones (3a–m), 6 mmol NBS, 25 mL CCl4 and 0.1 mmol
were added into a 50-mL round flask. The mixture refluxed about 11 h with an oil-
bath. The mixture was filtered after the reaction ended, and then the liquid mixture
was distilled with CCl4 in vacuum to get the residue.
Five mmol K2CO3 and 5 mmol KOH were added with stirring to a solution of the
resulting mixture and 6 mmol imidazole in anhydrous CH3CN (30 mL) at ambient
temperature under nitrogen atmosphere. The mixture was stirred for 12 h at ambient
temperature [monitored by thin layer chromatography (TLC)]. After removal of the
solvent under vacuum, the residue was purified on silica gel by a column using
petroleum ether/acetone (6:1) as the eluent to afford the title compound (Scheme 2
and Table 1).
5a: (E)-1-(4-((1H-imidazol-1-yl) methyl) phenyl)-3-phenylprop-2-en-1-one
White-solid; Yield: 16.8 %; mp: 68–70 °C; IR (KBr, cm-1): 1,649 (C=C); 1,581
(C=O); 1,610 (C=N); 3,034, 923 (ArH); 1H-NMR (400 MHz, DMSO-d6), d (ppm):
7.56 (d, 1H, Ha); 8.06 (d, 1H, Hb); 7.17–7.21 (d, 2H, H2, H6); 7.01–7.05 (d, 2H, H3,
H5); 7.54–7.46 (m, 3H, H30, H40, H50); 7.81–7.85 (d, 2H, H20, H60); 5, 08 (s, 2H,
CH2); 7.07–7.12 (d, 2H, CH=CH–N); 7.47 (S, 1H, CH=N); 13C-NMR (400 MHz,
Scheme 2 Synthetic of route for chalcone-imidazole derivatives 5a–m
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Y.-T. Liu et al.
Table 1 Antimicrobial activity of the newly synthesized compounds (lg/mL)
Comp. No.
Microorganisms and minimal inhibition concentration values
Sa
Bc
Ec
Pa
An
Af
5a
29.5
13.8
19.5
40.5
34
[50
11.6
[50
[50
38.5
16.5
45.2
[50
[50
[50
14.8
[50
[50
[50
0.39
0.78
[50
12.5
[50
[50
[50
15.6
15.6
45.6
40.5
49.7
22.5
14.9
[50
[50
3.9
[50
10.2
12.5
[50
11.7
13.8
3.1
22.5
9.5
25.8
7.3
5b
5c
12.5
12.5
16.5
12.5
10
12.5
25
5d
5e
18.5
21.7
12.5
[50
42.5
14.5
19.5
[50
42.8
3.9
5f
18.5
23.4
[50
25
5g
5h
5i
[50
23.5
19.4
12.7
[50
[50
[50
3.9
39.7
35.5
18.5
12.5
28.5
36.9
7.8
5j
[50
17.4
34.5
[50
[50
0.7
5k
5l
5m
Ket.
Kan.
Pen.
[50
[50
[50
[50
1.5
[50
[50
Sa Staphylococcus aureus ATCC 9144, Bc Bacillus cereus ATCC 11778, Ec Escherichia coli ATCC
25922, Pa Pseudomonas aeruginosa ATCC 43288, An Aspergillus niger ATCC 9092, Af Aspergillus
fumigatus ATCC 46645, Ket. Ketoconazole, Kan. Kanamycin, Pen. Penicillin
DMSO-d6), 191.78 (C=O), 126.81 (Ca), 144.23 (Cb), 134.48 (C1), 129.81 (C2, 6),
128.92 (C3, 5), 142.17 (C4), 135.27 (C10), 126.37 (C20, 60), 128.13 (C30, 50), 127.65
(C40), 67.78 (CH2), 136.58 (C100), 128.47 (C200), 122.94 (C300); Anal. Calcd. for
C19H16N2O (228.1584): C, 79.1954; H, 5.5964; N, 9.7217; Found: C, 79.1876; H,
5.5627; N, 9.7181.
5b: (E)-1-(4-((1H-imidazol-1-yl)methyl)phenyl)-3-(2-nitrophenyl)prop-2-en-1-one
White-Solid; Yield: 15.4 %; mp: 101–103 °C; IR (KBr, cm-1): 1,678 (C=C); 1,581
(C=O); 1,612 (C=N); 3,029, 848 (ArH); 1H-NMR (400 MHz, DMSO-d6), d (ppm):
5.05 (s, 2H, CH2); 7.01–7.09 (d, 2H, CH=CH–N); 7.25 (d, 2H, H3, H5); 7.40 (t, 1H,
H30); 7.51–7.63 (m, 4H, Ha, H50, H60, CH=N); 7.70 (d, 2H, H2, H6); 8.43 (d, 1H,
Hb); 8.14 (t, 1H, H30); 13C-NMR (400 MHz, DMSO-d6), 192.56 (C=O), 127.63
(Ca), 148.23 (Cb), 127.33 (C1), 145.18 (C2), 123.83 (C3), 128.96 (C4), 134.85
(C5), 127.38 (C6), 134.96 (C10), 129.87 (C20, 60), 129.35 (C30, 50), 127.93 (C40),
65.73 (CH2), 137.84 (C100), 128.67 (C200), 123.43 (C300); Anal. Calcd. for
C19H15N3O3 (333.3455): C, 68.4032; H, 4.5354; N, 12.6058; Found: C, 68.4077;
H, 4.5279; N, 12.6013.
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Syntheses and biological activity
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5c: (E)-1-(4-((1H-imidazol-1-yl)methyl)phenyl)-3-(3-nitrophenyl)prop-2-en-1-one
White-Solid; Yield: 23.7 %; mp: 143–145 °C; IR (KBr, cm-1): 1,678 (C=C); 1,567
(C=O); 1,611 (C=N); 3,025, 871, (ArH); 1H-NMR (400 MHz, DMSO-d6), d (ppm):
5.13 (s, 2H, CH2); 7.01–7.09 (d, 2H, CH=CH–N); 7.24 (d, 2H, H3, H5); 7.47–7.69
(m, 5H, H2, H6, H50, H60, CH=N); 7.79 (d, 1H, Ha); 8.07 (t, 1H, H30); 8.15 (d, 1H,
Hb); 8.26 (s, 1H, H20); 13C-NMR (400 MHz, DMSO-d6), 192.71 (C=O), 127.45
(Ca), 145.37 (Cb), 136.15 (C1), 120.13 (C2), 147.58 (C3), 123.17 (C4), 129.61
(C5), 132.54 (C6), 134.62 (C10), 129.73 (C20, 60), 129.82 (C30, 50), 128.27 (C40),
65.28 (CH2), 137.49 (C100), 128.34 (C200), 123.51 (C300); Anal. Calcd. for
C19H15N3O3 (333.3455): C, 68.4032; H, 4.5354; N, 12.6058; Found: C, 68.3984;
H, 4.5387; N, 12.6021.
5d: (E)-1-(4-((1H-imidazol-1-yl)methyl)phenyl)-3-(4-nitrophenyl)prop-2-en-1-one
Yellow-solid; Yield: 18.3 %; mp: 147–149 °C; IR (KBr, cm-1): 1,701 (C=C); 1,588
(C=O); 1,612 (C=N); 3,032, 865, (ArH); 1HNMR (DMSO-d6), d (ppm): 5.03 (s, 2H,
CH2); 7.01–7.08 (d, 2H, CH=CH–N); 7.28 (d, 2H, H3, H4); 7.56 (s, 1H, CH=N);
7.68 (d, 2H, H2, H6); 7.85 (d, 1H, Ha); 8.14 (d, 2H, H20, H60); 8.23 (d, 1H, Hb); 8,
56 (d, 2H, H30, H50); 13C-NMR (400 MHz, DMSO-d6), 192.77 (C=O), 127.22 (Ca),
148.12 (Cb), 141.35 (C1), 127.56 (C2, 6), 123.81 (C3, 5), 147.26 (C4), 134.95
(C10), 129.74 (C20, 60), 129.43 (C30, 50), 147.26 (C40), 66.38 (CH2), 138.58 (C100),
128.41 (C200), 123.47 (C300); Anal. Calcd. for C19H15N3O3 (333.3454): C, 68.4032;
H, 4.5354; N, 12.6058; Found: C, 68.3943; H, 4.5298; N, 9.7181.
5e: (E)-1-(4-((1H-imidazol-1-yl)methyl)phenyl)-3-(4-methoxyphenyl)
prop-2-en-1-one
Yellow-solid; Yield: 20.7 %; mp: 157–159 °C; IR (KBr, cm-1): 1,689 (C=C); 1,603
(C=O); 1,654 (C=N); 3,017, 831 (ArH); 1H-NMR (400 MHz, DMSO-d6), d (ppm):
3.81 (S, 3H, OCH3); 4.96 (S, 2H, CH2); 7.26–7.20 (m, 6H, Ha, Hb, H2, H3.H5.H6);
7.20 (d, 2H, N–CH=CH); 7.38 (d, 2H, H3, H5); 7.52 (d, 2H, H2, H5); 7.63 (S, 1H,
HC=N); 7.81–7.90 (m, 4H, H20, H30, H40, H60); 13C-NMR (400 MHz, DMSO-d6),
192.64 (C=O), 126.77 (Ca), 145.48 (Cb), 127.63 (C1), 127.56 (C2, 6), 114.85 (C3,
5), 159.91 (C4), 134.45 (C10), 129.82 (C20, 60), 129.65 (C30, 50), 142.15 (C40), 65.84
(CH2), 55.98 (OCH3), 137.62 (C100), 128.14 (C200), 123.47 (C300); Anal. Calcd. for
C20H18N2O2 (318.3742): C, 75.4521; H, 5.6984; N, 8.7991; Found: C, 75.4493; H,
5.6921; N, 8.8041.
5f: (E)-1-(4-((1H-imidazol-1-yl)methyl)phenyl)-3-(4-fluorophenyl)prop-2-en-1-one
Brown-solid; Yield: 17.5 %; mp: 163–165 °C; IR (KBr, cm-1): 1,697 (C=C); 1,573
(C=O); 1,639 (C=N); 3,017, 875 (ArH); 1H-NMR (400 MHz, DMSO-d6), d (ppm):
5.06 (s, 2H, CH2); 6.94 (d, 2H, H30, H40); 7.01–7.07 (d, 2H, CH=CH–N); 7.23 (d,
2H, H3, H5); 7.28 (d, 2H, H20, H60); 7.45 (d, 1H, Ha); 7.52 (s, 1H, CH=N); 8.09 (d,
1H, Hb); 7.68 (dd, 2H, H2, H6); 13C-NMR (400 MHz, DMSO-d6), 192.38 (C=O),
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126.92 (Ca), 144.67 (Cb), 130.81 (C1), 128.37 (C2, 6), 115.47 (C3, 5), 168.74 (C4),
135.48 (C10), 126.72 (C20, 60), 129.25 (C30, 50), 127.56 (C40), 66.89 (CH2), 137.21
(C100), 128.47 (C200), 123.16 (C300); Anal. Calcd. for C19H15N2OF (306.3385): C,
74.4957; H, 4.9352; N, 9.1448; F: 6.2016; Found: C, 74.4873; H, 4.9294; N, 9.1508;
F: 6.1943.
5g: (E)-1-(4-((1H-imidazol-1-yl)methyl)phenyl)-3-(4-chlorophenyl)prop-2-en-1-one
Brown-solid; Yield: 25.6 %; mp: 178–180 °C; IR (KBr, cm-1): 1,715 (C=C); 1,609
1
(C=O); 1,651 (C=N); 3,034, 895, 837 (ArH); H-NMR (400 MHz, DMSO-d6), d
(ppm): 5.11 (s, 2H, CH2); 7.02–7.08 (d, 2H, CH=CH–N); 7.22 (d, 2H, H30, H40);
7.26 (d, 2H, H20, H60); 7.39 (d, 1H, Ha); 7.31 (d, 2H, H3, H5); 7.58 (s, 1H, CH=N);
7.63 (dd, 2H, H2, H6); 8.07 (d, 1H, Hb); 13C-NMR (400 MHz, DMSO-d6), 191.94
(C=O), 126.92 (Ca), 143.85 (Cb), 129.14 (C1), 127.78 (C2, 6), 112.89 (C3, 5),
138.63 (C4), 135.84 (C10), 126.91 (C20, 60), 128.78 (C30, 50), 127.69 (C40), 66.48
(CH2), 137.67 (C100), 128.14 (C200), 123.68 (C300); Anal. Calcd. for C19H15N2OCl
(322.7935): C, 70.6981; H, 4.6836; N, 8.6786; Cl: 10.6734; Found: C, 70.6897; H,
4.6874; N, 8.6731; Cl: 10.6682.
5h: (E)-1-(4-((1H-imidazol-1-yl)methyl)phenyl)-3-(4-bromophenyl)prop-2-en-1-one
Light-brown-Solid; Yield: 28.4 %; mp: 111–113 °C; IR (KBr, cm-1): 1,679 (C=C);
1
1,583 (C=O); 1,621 (C=N); 3,009, 895 (ArH); H-NMR (400 MHz, DMSO-d6), d
(ppm): 4.94 (s, 2H, CH2); 7.01–7.09 (d, 2H, CH=CH–N); 7.19 (d, 2H, H20, H60);
7.28 (d, 2H, H20, H60); 7.29 (d, 2H, H3, H5); 7.38 (d, 2H, H30, H40); 7.47 (d, 1H,
Ha); 7.59 (s, 1H, CH=N); 7.71 (dd, 2H, H2, H6); 8.11 (d, 1H, Hb); 13C-NMR
(400 MHz, DMSO-d6), 192.56 (C=O), 126.23 (Ca), 145.48 (Cb), 129.08 (C1),
125.67 (C2, 6), 111.87 (C3, 5), 121.63 (C4), 136.08 (C10), 127.05 (C20, 60), 128.46
(C30, 50), 127.37 (C40), 65.89 (CH2), 137.48 (C100), 128.63 (C200), 123.56 (C300);
Anal. Calcd. for C19H15N2OBr (367.2445): C, 62.1409; H, 4.1167; N, 7.6282; Br:
21.7577; Found: C, 62.1367; H, 4.1103; N, 7.6199; Br: 21.7524.
5i: (E)-1-(4-((1H-imidazol-1-yl)methyl)phenyl)-3-(furan-2-yl)prop-2-en-1-one
Brown-solid; Yield: 16.9 %; mp: 116–118 °C; IR (KBr, cm-1): 1,711 (C=C); 1,603
(C=O); 1,631 (C=N); 3,004, 895, (ArH); 1H-NMR (400 MHz, DMSO-d6), d (ppm):
4.78 (S, 2H, CH2); 7.20 (d, 2H, NCH=CH); 7.28 (d, 1H, Ha); 7.30–7.63 (m, 3H, H2,
H3, H4); 7.65 (S, 1H, CH=N); 7.60–7.95 (m, 4H, H20, H30, H40, H60); 8.02 (d, 1H,
Hb); 13C-NMR (400 MHz, DMSO-d6), 187.48 (C=O), 127.41 (Ca), 131.54 (Cb),
151.62 (C1), 111.42 (C2), 112.76 (C3), 145.94 (C4), 134.85 (C10), 131.83 (C20, 60),
129.49 (C30, 50), 127.48 (C40), 66.75 (CH2), 138.13 (C100), 128.48 (C200), 123.51
(C300); Anal. Calcd. for C17H14N2O2 (278.1396): C, 73.4117; H, 5.0732; N,
10.0719; Found: C, 73.4318; H, 5.0692; N, 10.0631.
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Syntheses and biological activity
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5j: (E)-1-phenylprop-3-(4-((1H-imidazol-1-yl)methyl)phenyl)-2-en-1-one
White-solid; Yield: 23.5 %; mp: 84–86 °C; IR (KBr, cm-1): 1,689 (C=C); 1,593
(C=O); 1,631 (C=N); 3,034, 913 (ArH); 1H-NMR (400 MHz, DMSO-d6), d (ppm):
5.07 (S, 2H, CH2); 7.43–7.62 (m, 6H, Ha, Hb, H20, H30, H40, H50); 7.24 (d, 2H,
NCH=CH); 7.67 (s, 1H, CH=N), 7.85–7.93 (m, 4H, H2, H3, H5, H6); 8.01 (d, 1H,
H60); 13C-NMR (400 MHz, DMSO-d6), 192.55 (C=O), 125.43 (Ca), 143.78 (Cb),
127.17 (C1), 130.40 (C2, 6), 129.08 (C3, 5), 141.22 (C4), 137.92 (C10), 132.48 (C20,
60), 129.31 (C30, 50), 134.61 (C40), 69.34 (CH2), 136.84 (C100), 128.17 (C200), 120.74
(C300); Anal. Calcd. for C19H16N2O (288.1584): C, 79.1954; H, 5.5964; N, 9.7217;
Found: C, 79. 1903; H, 5.5921; N, 9.7195; N, 12.6058; Found: C, 68.3957; H,
4.5394; N, 12.6013.
5k: (E)-1-(4-fluorophenyl)phenylprop-3-(4-((1H-imidazol-1-yl)methyl)phenyl)-
2-en-1-one
White-solid; Yield: 19.4 %; mp: 79–81; IR (KBr, cm-1): 1,705 (C=C); 1,607
1
(C=O); 1,627 (C=N); 3,034, 895, 837 (ArH); H-NMR (400 MHz, DMSO-d6), d
(ppm): 4.98 (s, 1H, CH2); 7.08–7.16 (m, 4H, H20, H30, H50, H60); 7.24 (d, 2H,
NCH=CH); 7.49 (d, 1H, Hb); 7.61 (d, 1H, Ha); 7.65 (s, 1H, CH=N); 7.85–7.86 (m,
4H, H2, H3, H5, H6); 13C-NMR (400 MHz, DMSO-d6), 191.67 (C=O), 126.13
(Ca), 142.97 (Cb), 126.88 (C1), 131.18 (C2, 6), 128.92 (C3, 5), 140.79 (C4), 139.24
(C10), 133.88 (C20, 60), 129.35 (C30, 50), 165.37 (C40), 68.84 (CH2), 135.97 (C100),
128.58 (C200), 121.22 (C300); Anal. Calcd. for C19H15N2OF (306.3385): C, 74.4957;
H, 4.9352; N, 9.1448; F: 6.2016; Found: C, 74.4872; H, 4.9247; N, 9.1403; F:
6.1937.
5l: (E)-1-(4-bromophenyl)phenylprop-3-(4-((1H-imidazol-1-yl)methyl)phenyl)-
2-en-1-one
Yellow-Solid; Yield: 16.1 %; mp: 144–146 °C; IR (KBr, cm-1): 1,631 (C=C);
1,583 (C=O); 1,610 (C=N); 3,034, 895, 837 (ArH); H-NMR (400 MHz, DMSO-
1
d6), d (ppm): 5.08 (s, 1H, CH2); 7.15–7.57 (m, 8H, Ha, Hb, H2, H3, H5, H6,
NCH=CH); 7.68 (s, 1H, CH=N); 7.86–7.94 (m, 4H, H2, H3, H5, H6); 13C-NMR
(400 MHz, DMSO-d6), 192.43 (C=O), 127.13 (Ca), 144.35 (Cb), 126.48 (C1),
131.43 (C2, 6), 129.37 (C3, 5), 141.25 (C4), 138.53 (C10), 132.48 (C20, 60), 128.83
(C30, 50), 124.75 (C40), 69.27 (CH2), 136.62 (C100), 128.73 (C200), 123.35 (C300);
Anal. Calcd. for C19H15N2OBr (367.2445): C, 62.1409; H, 4.1167; N, 7.6282; Br:
21.7577; C, 62.1335; H, 4.1113; N, 7.6146; Br: 21.7597.
5m: (E)-1-(4-methoxyphenyl)phenylprop-3-(4-((1H-imidazol-1-yl)methyl)phenyl)-
2-en-1-one
Yellow-Solid; Yield: 22.5 %; mp: 124–126 °C; IR (KBr, cm-1): 1,721 (C=C);
1
1,613 (C=O); 1,632 (C=N); 3,034, 837 (ArH); H-NMR (400 MHz, DMSO-d6), d
(ppm): 3, 83 (s, 3H, OCH3); 4.82 (s, 1H, CH2); 7.21 (d, 2H, NCH=CH); 7.32–7.61
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Y.-T. Liu et al.
(m, 6H, Ha, Hb, H2, H3, H5, H6); 7.82–7.91 (m, 4H, H2, H3, H5, H6); 7.67 (s, 1H,
CH=N); 13C-NMR (400 MHz, DMSO-d6), 193.13 (C=O), 126.78 (Ca), 142.67
(Cb), 126.88 (C1), 131.35 (C2, 6), 129.43 (C3, 5), 142.19 (C4), 138.31 (C10),
133.57 (C20, 60), 120.14 (C30, 50), 168.45 (C40), 69.27 (CH2), 136.41 (C100), 127.92
(C200), 120.26 (C300), 53.18 (OCH3); Anal. Calcd. for C19H16N2O (318.3742): C,
75.4521; H, 5.6984; N, 8.7991; Found: C, 75.4467; H, 5.6932; N, 8.7914.
Antimicrobial activity
The antibacterial activity of the synthesized compounds was tested against
S. aureus, B. cereus, E. coli and P. aeruginosa using MH medium (Mueller–
Hinton medium: casein hydrolysate 18.5 g, soluble starch 1.5 g, beef extract
1,000 mL), and the antifungal activity of the compounds was tested against A. niger
and A. fumigatus using RPMI-1640 medium [RPMI-1640 (GIBCO BRL) 10 g,
NaHCO3 2.0 g, 0.15 mol/L morpholinepropanesulfonic acid (Sigma) 35 g, triple-
distilled water 900 mL, buffered to pH 7.0 with 1 mol/L NaOH (25 °C), metered
volume to 1,000 mL, filtered sterilization, conservation in 4 °C]. The MICs of the
test compounds were determined by a colorimetric method using the dye MTT [24].
A stock solution of the synthesized compound (50 lg/mL) in DMSO was prepared
and graded quantities of the test compounds were incorporated in a specified
quantity of sterilized liquid medium (MH medium for antibacterial activity and
RPMI-1640 medium for antifungal activity). A specified quantity of the medium
containing the compound was poured into microtitration plates. Suspension of the
microorganism was prepared to contain about 105 cfu/mL and applied to
microtitration plates with serially diluted compounds in DMSO to be tested and
incubated at 37 °C for 18 h and 36 h for bacteria and fungi, respectively. After the
MICs were visually determined on each of the microtitration plates, 50 lL of PBS
(phosphate buffered saline 0.01 mol/L, pH 7.5, Na2HPO4ꢀ12H2O 2.5 g, KH2PO4
0.2 g, NaCl 8.0 g, KCl 0.2 g, distilled water 1,000 mL) containing 2 mg of MTT/
mL was added to each well. Incubation was continued at room temperature for
5–6 h. The content of each well was removed, and 100 lL of isopropanol
containing 5 % 1 mol/L HCl was added to extract the dye. After 12 h of incubation
at room temperature, the optical density was measured with a microplate reader at
550 nm. The observed MICs are presented in Table 2.
Results
Chalcone (3a–m) synthesis by condensation of acetophenones and aldehydes under
the chosen conditions [25–28] (Scheme 1) is attractive since it especially generates
(E)-isomer, normally in high yield. As observed from 1H NMR spectra, all chalcones
were geometrically pure and with trans-configuration (J Ha–Hb = 15.5–16.0 Hz).
Using this method, 13 substituted chalcones (3a–m) were obtained in satisfactory
yields. Methyl on the aromatic ring of chalcones was brominated by NBS, and then the
123

Syntheses and biological activity
1045
Table 2 Prepared calcone-imidazole derivatives
Reagents
Products
Color
Yielda
(%)
mp (°C)
White solid
16.8
68–70
O
O
N
N
H
C
3
3a
5a
O
White solid
White solid
15.4
23.7
101–103
143–145
O
N
N
F
H
C
3
F
3b
5b
O
O
N
N
Cl
H
C
Cl
3
5c
3c
O
Yellow solid 19.4
Yellow solid 20.7
147–149
157–159
O
N
N
Br
H
C
Br
3
5d
3d
O
NO
2
O
NO
2
N
N
H C
3
5e
3e
O
Brown solid
Brown solid
17.5
25.6
163–165
178–180
O
NO2
NO2
N
N
H3
C
5f
3f
O
O
N
N
NO
2
H C
NO
2
3
5g
3g
O
Light-brown
solid
28.4
16.9
111–113
116–118
O
N
N
OCH
3
H3
C
OCH3
5h
3h
Brown solid
O
O
N
N
O
O
H3
C
5i
3i
123

1046
Y.-T. Liu et al.
Table 2 continued
Reagents
Products
Color
Yielda
(%)
mp (°C)
White solid
23.5
84–86
O
O
CH
3
N
3j
5j
N
White solid
18.3
79–81
O
O
F
CH
3
F
3k
N
5k
N
Yellow solid 16.1
144–146
124–126
O
O
Br
Br
CH
3
N
3l
5l
N
O
O
Yellow solid 22.5
H
CO
CH
3
H
CO
3
3
N
3m
5m
N
a
Isolated yield
resulting mixture was reacted with imidazole to get the target compounds. A novel
series of chalcone-imidazole derivatives were obtained in yields of 15.4–28.6 %.
The solid state IR (KBr, cm-1) spectra of these compounds showed C=N group
1
stretching vibrations are seen around 1,610 cm-1. The H NMR (DMSO-d6, ppm)
data of all compounds showed that the vibration of PhC-H 2.35 shifted to 4.90–5.1
confirming Ph–CH3 substituted by imidazole.
A problem was found in the process of synthesized compounds 4a–m that those
could not be purified in the traditional way, hence they are used in the subsequent
synthesis without purification. So, we used one-pot synthesis methods to get the title
compounds (5a–m). Steps were shown in chemistry.
The antibacterial activity results presented in Table 2 show the newly synthe-
sized compounds. These new derivatives were screened for their antibacterial
activity against E coli, P aeruginosa, S typhi, B subtilis and S aureus, in which these
compounds were tested against one or more bacterial strains. Compounds 5-b and
5-k showed higher activity against Gram-negative bacterial and Gram-positive
bacterial compared with others; meanwhile compound 5g showed higher activity
against Gram-negative bacterial strains while exhibited lower active against
123

Syntheses and biological activity
1047
Gram-positive bacterial strains, which might be due to the presence of a –F or –NO2
group. The potent activities of these chalcone-imidazole derivatives suggest that
they are potential candidates for the development of new antibacterial drugs.
The antifungal activity of the compounds was studied with two fungal strains
(Aspergillus niger ATCC 9092 and A. fumigatus ATCC 46645) by the MTT
method. The results are summarized in Table 2. Ketoconazole was used as reference
for inhibitory activity against fungi. All synthesized compounds exhibited anti-
fungal activity. These results revealed that some of the synthesized compounds
exhibited significant antibacterial activity and most of the synthesized compounds
showed better antifungal activity.
Conclusions
A novel series of chalcone-imidazole derivatives were characterized by IR,
1HNMR, 13C-NMR and elemental analyses. All the compounds were screened for
their antibacterial and antifungal activity. Most of the synthesized compounds
showed better antifungal activity. The antibacterial activity of compounds 5b, 5k
and 5g against Gram bacterial strains was found to be higher than that for the
standard drug.
Acknowledgment We are grateful to the Microbiology Institute of the Fourth Military Medical
University of China for providing the experiment strains.
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