Molecules 2021, 26, 2907
12 of 15
(12), 167 (14), 165 (11), 155 (11), 152 (11), 151 (26), 150 (14), 149 (23), 147 (11), 141 (12), 139
(15), 137 (13), 135 (11), 127 (12), 125 (21), 123 (19), 121 (11), 119 (11), 115 (14), 113 (14), 112
(14), 111 (36), 110 (11), 109 (27), 107 (15), 106 (16), 105 (16), 99 (17), 98 (13), 97 (52), 96 (16),
95 (36), 93 (12), 91 (27); HRMS m/z: [M]+calcd for C9H9N5O2: 219.0756; found: 219.0748.
N’-(1,3-Dioxo-5,6-dihydro-2H-benzo[f]isoindol-2-yl)-N,N-dimethylformimidamide (10): Light
yellow solid; 77% yield; mp 199–201 ◦C; 1H NMR (CDCl3, 400 MHz)
δ
3.05 (s, 3H, NMe),
3.07 (s, 3H, NMe), 7.64–7.69 (m, 2H, ArH), 7.84 (s, 1H), 7.99–8.02 (m, 2H, ArH), 8.28 (s, 2H,
ArH); 13C NMR (CDCl3, 100 MHz)
34.89, 41.10, 124.33 (2 C), 126.68 (2 C), 128.99 (2
C), 130.20 (2 C), 135.45 (2 C), 161.23, 166.00 (2
C) cm−1; FT-IR (KBr): 2918, 2807,
δ
×
×
×
×
×
×
1757, 1693, 1621, 1521, 1425, 1411, 1321, 1154, 1118, 1004, 900, 754, 479 cm−1; EIMS m/z: 268
(19), 267 (M+, 100), 225 (13), 210 (10), 198 (26), 197 (49), 180 (28), 155 (64), 154 (24), 153 (20),
152 (13), 140 (21), 127 (26), 126 (74), 71 (17), 57 (11); HRMS m/z: [M]+calcd for C15H13N3O2:
267.1008; found: 267.1015.
3.5. Standard Procedure for Preparation of Chlorination Products 5, and 11–15 from Phthalazine
1,4-Diones 3a–f with Vilsmeier Reagent (POCl3/DMF)
The reliable procedure that involved phthalazine 1,4-diones 3a–f (1.0 equiv.) was
individually treated with ~3.0 equivalent amount of POCl3 in N, N-dimethylformamide
solution (DMF, 2.0 mL) at 65 ◦C or 80 ◦C for 2–4 h. When the reaction was completed, the
reaction mixture was added to saturate sodium bicarbonate (15 mL) and extracted with
dichloromethane (15 mL). The organic extracts were dried over MgSO4, filtered, and con-
centrated under reduced pressure. The residues were purified by column chromatography
on silica gel to give the corresponding chlorinated products
5
in 80% yield and 11
–15 in
6,9-Dichloro-1,3-diphenyl-3H-pyrazolo[4’,3’:5,6]pyrido[3,4-d]pyridazine (
80% yield; mp 196–197 ◦C; 1H NMR (CDCl3, 500 MHz)
7.46 (t, J = 7.43 Hz, 1H, ArH),
7.49–7.51 (m, 3H, ArH), 7.57–7.60 (m, 4H, ArH), 8.17 (dd, J = 8.60, 1.09 Hz, 2H, ArH), 9.68
(s, 1H, ArH); 13C NMR (CDCl3, 125 MHz)
103.92, 118.46, 123.39 (2 C), 127.91, 127.95 (2
C), 128.19, 129.13, 129.33 (2 C), 130.01 (2 C), 135.22, 137.87, 147.79, 149.88, 151.00,
5): Light yellow solid;
δ
δ
×
×
×
×
152.05, 153.49; FT-IR (KBr): 3064, 2923, 2846, 1571, 1501, 1413, 1243, 1119, 863 cm−1; EIMS
m/z: 395 (12), 394 (17), 393 (M+ + 2, 65), 392 (36), 391 (M+, 99), 390 (20), 356 (20), 321 (35), 320
(60), 288 (14), 263 (12), 244 (33), 218 (17), 91 (19), 77 (100); HRMS calcd. For C20H11Cl2N5:
391.0392; found: 391.0397.
1,4-Dichlorophthalazine (11): Yellow solid; 90% yield; mp 162–164 ◦C; 1H NMR (CDCl3, 400
MHz)
δ δ
7.74–7.76 (m, 2H, ArH), 7.85–7.7.87 (m, 2H, ArH); 13C NMR (CDCl3, 100 MHz)
125.86 (2
×
C), 127.21 (2
×
C), 134.49 (2
×
C), 155.03 (2
×
C); IR (KBr): 3157, 3000, 2896,
2875, 1671, 1346, 1289, 1157, 993, 775, 664 cm−1; EIMS m/z: 202 (M+ + 4, 10), 200 (M+ + 2,
63), 198 (M+, 100), 182 (25), 180 (77), 172 (17), 170 (26), 151 (17), 135 (20), 128 (14), 125 (11),
123 (29), 102 (17), 101 (11), 99 (20), 90 (11). HRMS calcd. For C8H4Cl2N2: 197.9752; found:
197.9746.
◦
1
1,4-Dichloro-2,3-difluorophthalazine (12): White solid; 82% yield; mp 75–76 C; H NMR
(CDCl3, 400 MHz) 113.97
8.09 (t, J = 8.34 Hz, 2H, ArH); 13C NMR (CDCl3, 100 MHz)
(dd, J = 14.25, 7.66 Hz, 2 C), 125.19 (t, J = 5.23 Hz, 2 C), 153.50 (d, J = 16.46 Hz), 153.68
153.50 (2
δ
δ
×
×
×
C), 156.15 (d, J = 16.39 Hz); IR (KBr): 3143, 3068, 2836, 2782, 2718, 2611, 1625,
1571, 1539, 1511, 1389, 1218, 1161, 1104, 893, 814 cm−1; EIMS m/z: 238 (M+ + 4, 11), 236 (M+
+ 2, 78), 234 (M+, 100), 234 (30), 218 (12), 216 (36), 208 (24), 206 (38), 171 (27), 164 (30), 159
(18), 138 (11), 136 (16), 124 (10), 88 (15), 75 (11); HRMS calcd. For C8H2Cl2F2N2: 233.9563;
found: 233.9568.
1,4,6,7-Tetrachlorophthalazine (13): Light orange solid; 84% yield; mp 135–136 ◦C; 1H NMR
(CDCl3, 400 MHz)
(2 C), 140.2 (2
1242, 1130, 1035, 702, 663 cm−1; EIMS m/z: 270 (M+ + 2, 26), 270 (M+ + 2, 16), 268 (M+, 100),
δ
8.40 (s, 2H, ArH); 13C NMR (CDCl3, 100 MHz)
δ
126.07 (2
×
C), 127.39
×
×
C), 153.45 (2
×
C); IR (KBr): 3094, 1596, 1535, 1453, 1501, 1380, 1268,