May 2009
Reaction of 4,5-Dichloro-2-Chloromethylpyridazin-3(2H)-one with Phenols
413
(CDCl3): d 81.58, 124.51, 129.94, 134.90, 136.66, 137.53,
144.20, 155.33, 156.82 ppm; Elemental analysis calcd. for
C12H7Cl4N3O4: C, 36.12; H, 1.77; N, 10.53. Found: C, 36.17;
H, 1.79; N, 10.57.
2-[(4,5-Dichloro-6-oxopyridazin-l(6H)-yl)methoxy]-3-metho-
xybenzaldehyde (4a). Prepared by the Method 1 and 2. mp
143ꢁC. IR (KBr) 3077, 3011, 2993, 2885, 2846, 1695, 1666,
1615, 1581, 1481, 1460, 1392, 1278, 1250,1217 cmꢂ1 1H
;
the reaction is effected by the base, the solvent, and/or
the substitutes of phenols. Further work including the
theoretical study on the regiochemistry and the biologi-
cal activity are under way in our laboratory.
EXPERIMENTAL
Melting points were determined with a capillary apparatus
1
NMR (CDCl3): d 3.91 (s, 3H), 6.09 (s, 2H, N-CH2), 7.16 (d,
2H, J ¼ 3 Hz), 7.34 (t, 1H, J ¼ 5.1 Hz), 7.72 (s, 1H), 10.16
ppm (s, 1H); 13C NMR (CDCl3): d 56.21, 81.44, 117.99,
119.41, 125.34, 129.93, 134.87, 136.33, 137.20, 148.32,
152.35, 156.58, 189.73 ppm; Elemental analysis calcd. for
C13H10Cl2N2O4: C,47.44; H,3.06; N, 8.51; Found: C, 47.49;
H, 3.11; N, 8.58.
4,5-Dichloro-2-[(2,6-dichlorophenoxy)methyl]pyridazin-
3(2H)-one (4c). Prepared by the Method 1. mp 142ꢁC. IR
(KBr) 3093, 3053, 1676, 1663, 1584, 1456, 1440, 1402, 1297,
1242, 1224, 1003, 990, 962 cmꢂ1 1H NMR (CDCl3): d 6.03
;
(s, 2H), 7.05 (t, 1H, J ¼ 8.15 Hz), 7.29 (m, 2H), 7.72 ppm (s,
1H); 13C NMR (CDCl3): d 81.46, 126.17, 129.07, 129.14,
134.84, 136.12, 137.17, 149.68, 156.80 ppm; Elemental analy-
sis calcd. for C11H6Cl4N2O2: C, 38.86; H, 1.78; N, 8.24.
Found: C, 38.90; H, 1.82; N, 8.27.
4,5-Dichloro-2-((2,4-dinitrophenoxy)methyl)pyridazin-
3(2H)-one (4j). Prepared by the Method 1. mp 147–149ꢁC. IR
(KBr) 3095, 3062, 1681, 1607, 1586, 1525, 1349, 1273, 1249,
;
987, 964 cmꢂ1 1H NMR (CDCl3): d 6.24 (s, 2H), 7.75 (d,
and uncorrected. H and 13C NMR spectra were recorded on a
300 MHz spectrophotometer with chemical shift values
reported in d units (ppm) relative to an internal standard
(TMS). IR spectra were obtained on an IR spectrophotometer.
Elemental analyses were performed with a CHNS-932 (Leco).
2-Chloromethyl-4,5-dichloropyridazin-3(2H)-one was synthe-
sized by the literature method [2]. Microwave reaction was
carried out by using a CEM, Discover microwave apparatus.
General procedure for the reaction of 2-chloromethyl-4,5-
dichloropyridazin-3(2H)-one (1) with phenols (2).
Method 1. A solution of 2-hydroxy-3-methoxybenzaldehyde
(2.8 g, 2 equiv.) and base (2 equiv.), 2-chloromethyl-4,5-
dichloro-pyridazin-3(2H)-one (2) (2 g, 1 equiv.), and solvent
(30 mL) was refluxed until 2 disappeared by TLC monitoring.
After cooling the mixture to room temperature, the mixture
was filtered and concentrated. The distribution of products was
1
analyzed by H NMR quantitative analysis. The products 3, 4,
and 5 were also isolated by column chromatography on silica
gel (2.5 ꢀ 8 cm) with n-hexane/EtOAc (2:1, v/v).
Method 2. 2-Chloromethyl-4,5-dichloropyridazin-3(2H)-one
(2) (0.1 g, 1 equiv.) was dissolved in solvent (7 mL) in a 10
mL microwave vessel. 2-Hydroxy-3-methoxybenzaldehyde
(0.14 g, 2 equiv.) and base (2 equiv.) were added. The vessel
was closed and placed into a microwave apparatus. The mix-
ture was irradiated per 10 min at 120ꢁC with a set power of
300 W. After cooling, the mixture was filtered on a glass filter
under vacuum. The distribution of products was analyzed by
1H NMR quantitative analysis.
1H, J ¼ 9.24 Hz), 7.90 (s, 1H), 8.47 (dd, 1H, J ¼ 2.77, 6.45
Hz), 8.70 ppm (d, 1H, J ¼ 2.74 Hz); 13C NMR (CDCl3): d
79.10, 117.90, 121.72, 128.99, 135.14, 137.46, 137.85, 140.17,
141.90, 154.30, 156.62 ppm; Elemental analysis calcd. for
C11H6Cl2N4O6: C, 36.59; H, 1.67; N, 15.52. Found: C, 36.63;
H, 1.70; N, 15.58.
2-(5-Chloro-l-((2-formyl-6-methoxyphenoxy)methyl)-6-oxo-
l,6-dihydropyridazin-4-yloxy)-3-methoxybenzaldehyde (5a).
Prepared by the Method 1 and 2. mp 165ꢁC. IR (KBr): 3085,
3021, 2988, 2946, 2843, 1694, 1663, 1617, 1584, 1482, 1461,
2-(5-Chloro-l-chloromethyl-6-oxo-l,6-dihydropyridazin-4-
yloxy)-3-methoxybenzaldehyde (3a). Prepared by the Method
1 and 2. mp; 145ꢁC. IR (KBr) 3081, 3045, 2935, 2878, 1663,
1394, 1377, 1312, 1271, 1248, 990 cmꢂ1 1H NMR (CDCl3):
;
1
1581, 1479, 1452, 1387, 1254, 1213 cmꢂ1; H NMR (CDCl3):
d 3.86 (s, 3H), 3.96 (s, 3H), 6.15 (s, 2H), 7.19 (d, 2H, J ¼ 6
Hz), 7.28 (t, 1H, J ¼ 4.5 Hz), 7.33 (s, 1H), 7.38 (t, 1H, J ¼
3.8 Hz), 7.43 (s, 1H, J ¼ 8.1 Hz), 7.56 (dd, 1H, J ¼ 1.2, 7.7
Hz), 10.19 (s, 1H, CHO), 10.31 ppm (s, 1H, CHO); 13C NMR
(CDCl3): d 56.20, 56.44, 80.85, 117.91, 118.21, 119.00,
120.74, 125.27, 127.52, 129.15, 129.41, 142.98, 151.15,
152.49, 153.71, 187.80, 189.82 ppm; Elemental analysis calcd.
for C21H17ClN2O7: C, 56.70; H, 3.85; N, 6.30; Found: C,
56.75; H, 3.87; N, 6.34.
4-Chloro-5-(2,6-dichlorophenoxy)-2-[(2,6-dichloro-phen-
oxy)-methyl]pyridazin-3(2H)-one (5c). Prepared by the
Method 1. mp 145–147ꢁC. IR (KBr): 3074, 3054, 2923, 1674,
1445, 1270 1237 cmꢂ1 1H NMR (CDCl3): d 6.04 (s, 2H),
;
7.05 (m, 1H), 7.29 (m, 3H), 7.44 (d, 2H, J ¼ 8.11 Hz), 7.72
ppm (s, 1H); 13C NMR (CDCl3): d 81.15, 126.04, 126.17,
128.11, 128.16, 128.98, 129.07, 129.25, 129.47, 136.12,
145.21, 152.46, 158.90 ppm; Elemental analysis calcd. for
C17H9Cl5N2O3: C, 43.77; H, 1.94; N, 6.00. Found: C, 43.79;
H, 2.00; N, 6.07.
4-Chloro-5-(2,5-dichlorophenoxy)-2-[(2,5-dichlorophenoxy)-
methyl]pyridazin-3(2H)-one (5d). Prepared by the Method 1.
mp 143ꢁC. IR (KBr): 3073, 3057, 3018, 1659, 1612, 1578,
d 3.87 (s, 3H), 5.86 (s, 2H, N-CH2), 7.35 (d, 1H, J ¼ 6 Hz),
7.42 (s, 1H), 7.46 (t, 1H, J ¼ 6 Hz), 7.58 (d, 1H, J ¼ 6 Hz),
10.30 ppm (s, CHO 1H); 13C NMR (CDCl3): d 56.55, 58.29,
118.31, 121.12, 127.71, 129.26, 130.17, 142.79, 151.25,
153.83, 157.77, 187.75 ppm; Elemental analysis calcd. for
C13H10Cl2N2O4: C,47.44; H,3.06; N, 8.51; Found: C, 47.50;
H, 3.10; N, 8.57.
4-Chloro-2-(chloromethyl)-5-phenoxypyridazin-3-(2H)-one
(3b). Prepared by the Method 1. mp 78ꢁC. IR (KBr) 3067,
3011, 1660, 1609, 1585, 1487, 1393, 1311, 1278, 1216, 1155
cmꢂ1
;
1H NMR (CDCl3): d 5.85 (s, 2H), 7.11 (d, 2H, J ¼
7.64 Hz), 7.32 (m, 1H), 7.48 (m, 2H), 7.53 ppm (s, 1H); 13C
NMR (CDCl3): d 58.29, 115.99, 119.79, 126.42, 130.55,
130.62, 131.23, 153.31, 153.72 ppm; Elemental analysis calcd.
for C11H8Cl2N2O2: C, 48.73; H, 2.97; N, 10.33. Found: C,
48.80; H, 3.00; N, 10.37.
4-Chloro-2-chloromethyl-5-[(2,6-dichloro-4-nitrophenoxy)
methyl]pyridazin-3(2H)-one (3e). Prepared by the Method 1.
mp 152ꢁC. IR(KBr) 3086, 3054, 1678, 1588, 1523, 1506,
1
1349, 1293, 1249, 1215, 973, 956 cmꢂ1; H NMR (CDCl3): d
6.11 (s, 2H), 7.77 (s, 1H), 8.21 ppm (s. 2H); 13C NMR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet