J. Rojas et al. / European Journal of Medicinal Chemistry 37 (2002) 699–705
703
expression of those inducible enzymes involved in their
production, could be an important strategy to obtain
promising anti-inflammatory agents.
4.1.3. 4-Dimethylamino-4%-methylchalcone (3)
Yield 94%, m.p.: 80–81 °C. IR (KBr): 1654 (CꢀO),
1
1595 (CꢀC) cm−1. H-NMR (CDCl3) l: 7.94 (dd, 2H,
J=8.11, 2.02 Hz, H-2%, H-6%), 7.42 (d, 1H, J=15.83
Hz, H-b), 7.60 (d, 1H, J=15.83 Hz, H-a), 7.34 (dd,
2H, J=8.11, 2.2 Hz, H-3%, H-5%), 6.75 (dd, 1H, J=8.7,
1.88 Hz, H-6), 6.72 (dd, 1H, J=8.7, 1.88 Hz, H-2),
6.55 (dd, 2H, J=8.7, 2.6 Hz, H-3, H-5), 2.83 (s, 6H,
N(CH3)2), 2.45 (s, 3H, CH3). m/z 266 [M+1]. Anal.
C18H19NO.
4. Experimental
4.1. General procedure for the synthesis of dimethy-
lamino-chalcone deri6ati6es
Melting points were measured on a Thomas–Hoover
Unimelt apparatus and are uncorrected. Thin layer
chromatography (TLC, silica gel 60 GF254, Merck,
Darmstadt) was used to monitor reactions and check
product homogeneity. IR spectra were recorded as KBr
pellets using a Shimadzu model 470 spectrometer. Nu-
clear Magnetic Resonance 1H-NMR spectra were
recorded on a JEOL GSX 270 MHz spectrometer (te-
tramethylsilane as internal standard). Splitting patterns
are described as singlet (s), doublet (d), triplet (t),
quartet (q) and multiplet (m). NMR values are given in
l units relative to CDCl3. Mass spectrometry (m/z)
spectra were obtained using a Hewlett Packard HP
5971A with Mass Selective Detector. Elemental analy-
ses were performed by Atlantic Microlab Inc., Nor-
cross, GA. Results were within 90.4% of predicted
values for all compounds.
A substituted methyl ketone (1 mmol), and a substi-
tuted aldehyde (1 mmol) were dissolved in a minimum
amount of methanol (normally 2–4 ml). A single
NaOH pellet (about 100 mg) was then added to this
solution. The reaction mixture was stirred at r.t. In
most cases, off-white to bright yellow solids were
formed within a few minutes to 24 h (Table 1). The
solids were collected on a filter and washed with cold
methanol. Chalcones were recrystallized using EtOAc/
hexane (3:7).
4.1.4. 4-Dimethylamino-2%,4%-dimethoxychalcone (4)
Yield 80%, m.p.: 84–85 °C. IR (KBr): 1644 (CꢀO),
1
1590 (CꢀC) cm−1. H-NMR (CDCl3) l:7.68 (d, 2H,
J=8.66, H-3, H-5), 7.64 (d, 1H, J=15.59 Hz, H-b),
7.47 (d, 2H, J=8.91 Hz, H-2, H-6), 7.26 (d, 1H,
J=15.83 Hz, H-a), 6.64 (d, 1H, 8.91 Hz, H-6%), 6.51
(dd, 1H, J=2.99, 2.23 Hz, H-3%), 6.48 (dd, 1H, J=
8.91, 2.2 Hz, H-5%), 3.86 (s, 3H, OCH3), 3.84 (s, 3H,
OCH3), 3.00 (s, 6H, N(CH3)2). m/z 312 [M+1]. Anal.
C19H21NO3.
4.1.5. 4-Dimethylamino-2%,6%-dimethoxychalcone (5)
Yield 85%, m.p.: 190–101 °C. IR (KBr): 1644
(CꢀO), 1590 (CꢀC) cm−1. 1H-NMR (CDCl3) l: 7.39 (d,
2H, J=8.9 Hz, H-3, H-5), 7.30 (t, 1H, J=8.41 Hz,
H-4%), 7.26 (d, 1H, J=16.82 Hz, H-b), 6.76 (d, 1H,
J=16.82 Hz, H-a), 6.62 (d, 2H, J=10.64 Hz, H-5%,
H-3%), 6.58 (d, 2H, J=8.41 Hz, H-2, H-6), 3.7 (s, 6H,
(OCH3)2, 2.98 (s, 6H, N(CH3)2). m/z 312 [M+1]. Anal.
C19H21NO3.
4.1.6. 4-Dimethylamino-2%,5%-dimethoxychalcone (6)
Yield 90%, m.p.: 190–101 °C. IR (KBr): 1644
1
(CꢀO), 1590 (CꢀC) cm−1. H-NMR (CDCl3) l: 7.55
(d, 1H, J=15.83 Hz, H-b), 7.46 (d, 2H, J=8.66 Hz,
H-3%, H-4%), 7.30 (d, 1H, J=15.83 Hz, H-a), 7.11 (d, H,
J=2.2 Hz, H-6%), 6.96 (dd, 2H, J=8.91, 3.22 Hz, H-2,
H-6),), 6.92 (d, 1H, J=8.91 Hz, H-3), 6.65 (d, 1H,
J=8.91 Hz, H-5), 3.81 (s, 3H, OCH3), 3.78 (s, 3H,
OCH3), 2.98 (s, 6H, N(CH3)2. m/z 312 [M+1]. Anal.
C19H21NO3.
4.1.1. 4-Dimethylamino-chalcone (1)
Yield 90%, m.p.: 58–59 °C. IR (KBr): 1644 (CꢀO),
1
1568 (CꢀC) cm−1. H-NMR (CDCl3) l: 7.96 (m, 2H,
H-2%, H-6%), 7.55 (m, 3H, H-3%, H-4%, H-5%) 7.43 (d, 1H,
J=16 Hz, H-b), 7.29 (d, 1H, J=16 Hz, H-a), 6.75 (dd,
1H, J=8.7, 1.8 Hz, H-6), 6.72 (dd, 1H, J=8.7, 1.8 Hz,
H-2), 6.57 (dd, 1H, J=8.7, 2.6 Hz, H-5), 6.55 (dd, 1H,
J=8.7, 2.6 Hz, H-3), 2.83 (s, 6H, N(CH3)2). m/z 252
[M+1]. Anal. C17H17NO.
4.1.7. 4-Dimethylamino-3%,4%-dichlorochalcone (7)
Yield 98%, m.p.: 118–119 °C. IR (KBr): 1644
(CꢀO), 1590 (CꢀC) cm−1. 1H-NMR (CDCl3) l: 8.06 (d,
1H, J=1.98 Hz, H-2%), 7.82-7.76 (m, 2H, H-b, H-6%),
7.52 (d, 4H, J=9.40, H-2, H-3, H-6, H-5), 7,21 (d, 1H,
J=15.59, H-a), 6.67 (d, 1H, J=8.91 Hz, H-5%), 2.98 (s,
6H, N(CH3)2). Anal. C17H15Cl2NO.
4.1.2. 4-Dimethylamino-3%,4%,5%-trimethoxychalcone (2)
Yield 80%, m.p.: 128–129 °C. IR (KBr): 1644
1
(CꢀO), 1590 (CꢀC) cm−1. H-NMR (CDCl3) l:7.46 (d,
1H, 15.59 Hz, H-b), 7.29 (d, 1H, J=15.59 Hz, H-a),
7.13 (d, 2H, H-2%, H-5%), 6.72 (dd, 1H, J=8.7, 1.88 Hz,
H-6), 6.71 (dd, 1H, J=8.7, 1.88 Hz, H-2), 6.55 (dd,
2H, J=8.7, 2.67 Hz, H-3, H-5), 3.93 (s, 9H, (OCH3)2).
m/z 342 [M+1]. Anal. C20H23NO4.
4.1.8. 4-Dimethylamino-2%,5%-dichlorochalcone (8)
Yield 88%, m.p.: 100–101 °C. IR (KBr): 1644
1
(CꢀO), 1590 (CꢀC) cm−1. H-NMR (CDCl3) l: 7.93 (s,
1H, H.6%), 7.42–7.35 (m, 4H, H-2, H-3, H-5, H-b), 7.32
(d, 2H, J=8.1 Hz, H-3%, H-4%), 7.31–6.62 (m, 3H, H-a,