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A.M. Balan et al. / European Journal of Medicinal Chemistry 44 (2009) 2275e2279
(Caution: It is hazardous to heat rapidly the reactions with
microwave irradiation. Therefore, caution should be exercised
when conducting reactions of this type).
H5, J ¼ 5.6, J ¼ 8.0; 8.76e8.73, td, 1H: H4, J ¼ 5.2, J ¼ 8.0;
7.53e7.49, m, 2H: H10, H14; 7.04e7.02, d, 1H: H13, J ¼ 8.4;
6.68, s, 2H: CH2; 13C NMR (DMSO-d6): dppm: 188.08 (CO),
154.53 (C3), 152.63 (C12), 151.75 (C6), 145.76 (C11), 137.24
(C4), 135.80 (C5), 124.88 (C9), 122.09 (C10), 115.59 (C13),
115.17 (C14), 69.72 (CH2).
2-Chloro-30,40-dihydroxyacetophenone (1.86 g, 10 mmol, in
10 mL anhydrous methanol) was placed in the reaction vessel
(Pyrex glass or quartz). Diazine compound (10.5 mmol), dis-
solved/suspended in anhydrous benzene [2 mL (for 3b),
50 mL (for 3a) and 20 mL (for the rest)] was then added. The
tube is then placed in the microwave cell and heated for the ap-
propriate time. Stirring of the reaction mixture is desirable.
When the stirring device is not accessible, it could be replaced
with continuously babbling nitrogen into the reaction system.
Once the heating cycle is complete and tube was cooled to am-
bient temperature, the tube was removed, and the cycloimmo-
nium salts were filtered off, washed 2 times with 10 mL of dry
acetone and dried in vacuo. No other purification required.
4.1.3.2. 1-[2-(3,4-Dihydroxyphenyl)-2-oxo-ethyl]-3-methylpyr-
idazin-1-ium chloride (2b). White crystals; mp 243e245 ꢁC;
Anal. C13H13ClN2O3 (C, H, N); IR (KBr): n/cmꢂ1: 3431
(eOeH), 3061 (CeHarom), 2981 (CeHalif), 1682 (COcet),
1
1598, 1526, 1451 (C]C, C]Narom); H NMR (DMSO-d6):
dppm: 10.46, s (broaded), 1H: OH (12); 9.81e9.80, d, 1H:
H6, J ¼ 5.6; 9.67, s (broaded), 1H: OH (11); 8.74e8.71, td,
1H: H5, J ¼ 5.6, J ¼ 8.4; 8.63e8.61, d, 1H: H4, J ¼ 8.4;
7.53e7.50, dd, 1H: H14, J ¼ 8.4, J ¼ 2.0; 7.466e7.461, d,
1H: H10, J ¼ 2.0; 7.01e6.99, d, 1H: H13, J ¼ 8.4; 6.57, s,
2H: CH2; 2.80, s, 3H: CH3; 13C NMR (DMSO-d6): dppm
:
4.1.3. General procedure for the syntheses of
188.05 (CO), 164.59 (C3), 152.56 (C12), 149.52 (C6), 145.53
(C11), 138.03 (C4), 134.79 (C5), 124.91 (C9), 122.09 (C10),
115.52 (C13), 115.02 (C14), 69.05 (CH2), 21.47 (CH3).
cycloimmonium salts (2, 3) under ultrasounds irradiation
Ultrasound assisted reactions were carried out using a Sonics
reactor (Sonics VCX-130, USA), and, the best results were obtained
applying a pulse irradiation (5 s pulse/5 s pause, 50% from the
full power of the generator). A typical device is presented below.
4.1.3.3. 3-(4-Bromophenyl)-1-[2-(3,4-dihydroxyphenyl)-2-oxo-
ethyl]-pyridazin-1-ium chloride (2c). Brownish crystals; mp
246e248 ꢁC; Anal. C18H14BrClN2O3 (C, H, N); IR (KBr):
n/cmꢂ1: 3438 (eOeH), 3014 (CeHarom), 2943 (CeHalif),
1683 (COcet), 1595, 1515, 1432 (C]C, C]Narom); 1H
NMR (DMSO-d6): dppm: 9.91e9.90, d, 1H: H6, J ¼ 5.6;
9.28e9.26, d, 1H: H4, J ¼ 8.8; 8.92e8.89, td, 1H: H5,
0
J ¼ 5.6, J ¼ 8.8; 8.17e8.15, d, 2H: H2 , J ¼ 8.4; 7.89e7.87,
0
d, 2H: H3 , J ¼ 8.4; 7.58e7.55, dd, 1H: H14, J ¼ 8.4, J ¼ 2.0;
7.496e7.491, d, 1H: H10, J ¼ 2.0; 7.03e7.01, d, 1H: H13,
J ¼ 8.4; 6.59, s, 2H: CH2; 13C NMR (DMSO-d6): dppm
:
187.79 (CO), 160.18 (C3), 152.29 (C12), 149.89 (C6), 145.49
0
(C11), 136.16 (C4), 134.41 (C5), 132.55 (C3 ), 130.86 (C1 ),
0
0
0
129.81 (C2 ), 126.73 (C4 ), 124.95 (C9), 122.24 (C10), 115.43
(C13), 114.87 (C14), 69.12 (CH2).
4.1.3.4. 3-(4-Methylphenyl)-1-[2-(3,4-dihydroxyphenyl)-2-oxo-
ethyl]-pyridazin-1-ium chloride (2d). Cream-coloured crys-
tals; mp 236e238 ꢁC; Anal. C19H17ClN2O3 (C, H, N); IR
(KBr): n/cmꢂ1: 3432 (eOeH), 3064 (CeHarom), 2984 (Ce
Halif), 1684 (COcet), 1596, 1521, 1450 (C]C, C]Narom);
1H NMR (DMSO-d6): dppm: 10.50, s (broaded), 1H: OH
(12); 9.94e9.92, d, 1H: H6, J ¼ 5.6; 9.70, s (broaded), 1H:
OH (11); 9.28e9.27, d, 1H: H4, J ¼ 8.4; 8.91e8.89, td, 1H:
A
solution of 2-chloro-30,40-dihydroxyacetophenone
(10 mmol, in 10 mL methanol) and diazine compound
(10.5 mmol) in dry acetone [2 mL (for 3b), 50 mL (for 3a)
and 20 mL (for the rest)], was exposed to ultrasounds for the
appropriate time. The obtained diazine salts were filtered
off, washed 2 times with 10 mL of dry acetone and dried in
vacuo. No other purification required.
0
H5, J ¼ 5.6, J ¼ 8.4; 8.14e8.12, d, 2H: H2 , J ¼ 8.4; 7.56e
0
7.37, m, 4H: H10, H14, 2H3 ; 7.05e7.03, d, 1H: H13, J ¼ 8.4;
6.73, s, 2H: CH2; 2.41, s, 3H: CH3; 13C NMR (DMSO-d6):
dppm: 186.34 (CO), 160.14 (C3), 152.23 (C12), 149.84 (C6),
0
145.46 (C11), 138.49 (C4 ), 136.11 (C4), 134.39 (C5), 133.96
4.1.3.1. 1-[2-(3,4-Dihydroxyphenyl)-2-oxo-ethyl]-pyridazin-1-
ium chloride (2a). Yellow crystals; mp 230e232 ꢁC; Anal.
C12H11ClN2O3 (C, H, N); IR (KBr): n/cmꢂ1: 3431 (eOeH),
0
(C1 ), 130.14 (C3 ), 126.12 (C2 ), 124.91 (C9), 122.19 (C10),
0
0
115.37 (C13), 114.82 (C14), 69.01 (CH2), 21.23 (CH3).
3087 (CeHarom), 2977 (CeHalif), 1679 (C]O), 1652, 1596,
:
10.50, s (broaded), 1H: OH (12); 10.03e10.02, d, 1H: H6,
J ¼ 5.6; 9.73e9.72, m, 2H: H3, OH (11); 8.90e8.97, td, 1H:
1
1521, 1456 (C]C, C]Narom); H NMR (DMSO-d6): dppm
4.1.3.5. 1-[2-(3,4-Dihydroxyphenyl)-2-oxo-ethyl]-3-hydroxy-
pyrimidin-1-ium chloride (3a). Beige crystals; mp 242e
244 ꢁC; Anal. C12H11ClN2O4 (C, H, N); IR (KBr): n/cmꢂ1: 3419