PAPER
One-Pot Synthesis of Phthalazinones
1805
MS: m/z (%) = 252 (100) [M+], 237 (36), 207 (15), 130 (15), 122
(19), 121 (39), 76 (17).
7,8-Dimethoxy-2-(2,5-dimethylphenyl)-1(2H)-phthalazinone
(Table 3, Entry 6)
Orange solid; mp 93–95 °C (CH2Cl2–MeOH, 99:1).
7,8-Dimethoxy-1(2H)-phthalazinone (Table 3, Entry 1)
Yellow-orange crystals; mp 162–164 °C (CH2Cl2–MeOH, 95:5).
1H NMR (300 MHz, CDCl3): d = 8.07 (s, 1 H, Ar), 7.48 (d, J = 8.7
Hz, 1 H, Ar), 7.43 (d, J = 8.7 Hz, 1 H, Ar), 7.08–7.21 (m, 3 H, Ar),
3.97 (s, 3 H, CH3), 3.96 (s, 3 H, CH3), 2.32 (s, 3 H, CH3), 2.13 (s,
3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 157.2, 155.7, 148.8, 140.8, 137.7,
136.5, 131.8, 130.7, 129.4, 127.8, 124.8, 123.1, 122.5, 118.3, 61.9,
56.5, 20.8, 17.1.
1H NMR (300 MHz, CDCl3): d = 10.3 (s, 1 H, NH), 8.01 (s, 1 H,
Ar), 7.48 (d, J = 8.7 Hz, 1 H, Ar), 7.46 (d, J = 8.7 Hz, 1 H, Ar), 4.01
(s, 3 H, CH3), 4.00 (s, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 158.9, 155.4, 148.5, 138.6, 123.2
(2×), 122.2, 118.5, 62.1, 56.5.
MS: m/z (%) = 206 (32) [M+], 191 (100), 189 (49), 177 (42), 160
MS: m/z (%) = 310 (76) [M+], 293 (100), 277 (25), 251 (19), 205
(41), 146 (47), 118 (25), 63 (97).
(37), 190 (20), 77 (73).
7,8-Dimethoxy-2-phenyl-1(2H)-phthalazinone (Table 3, Entry
2)
7,8-Dimethoxy-2-(2-ethylphenyl)-1(2H)-phthalazinone (Table
3, Entry 7)
Orange solid; mp 174–176 °C (CH2Cl2–MeOH, 95:5).
Light-yellow crystals; mp 94–96 °C (CH2Cl2–MeOH, 99:1).
1H NMR (300 MHz, CDCl3): d = 8.42 (d, J = 7.8 Hz, 1 H, Ar), 8.11
(s, 1 H, Ar), 7.45–7.80 (m, 6 H, Ar), 4.01 (s, 3 H, CH3), 3.99 (s, 3 H,
CH3).
13C NMR (75 MHz, CDCl3): d = 159.8, 154.9, 137.9, 135.6, 132.7,
131.0, 129.3, 128.7, 126.5, 126.0, 125.2, 118.3, 61.9, 56.5.
MS: m/z (%) = 282 (48) [M+], 267 (100), 253 (18), 235 (22), 149
(21), 91 (23), 77 (90).
1H NMR (300 MHz, CDCl3): d = 8.10 (s, 1 H, Ar), 7.52 (d, J = 8.7
Hz, 1 H, Ar), 7.46 (d, J = 8.7 Hz, 1 H, Ar), 7.31–7.40 (m, 4 H, Ar),
4.01 (s, 3 H, CH3), 3.98 (s, 3 H, CH3), 2.55 (q, J = 7.5 Hz, 2 H,
CH2), 1.16 (t, J = 7.5 Hz, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 157.5, 155.8, 149.0, 140.8, 137.6,
129.0, 128.9, 127.7, 126.8, 125.0, 123.1, 122.6, 118.4, 116.4, 62.0,
56.5, 24.0, 14.0.
MS: m/z (%) = 310 (36) [M+], 295 (100), 293 (83), 281 (40), 263
7,8-Dimethoxy-2-(3-methylphenyl)-1(2H)-phthalazinone
(Table 3, Entry 3)
(38), 190 (28), 118 (45), 104 (34).
Orange solid; mp 78–80 °C (CH2Cl2–MeOH, 99:1).
7,8-Dimethoxy-2-(tert-butyl)-1(2H)-phthalazinone (Table 3,
Entry 8)
Colorless oil; (CH2Cl2–MeOH, 95:5).
1H NMR (300 MHz, CDCl3): d = 7.77 (s, 1 H, Ar), 7.03–7.15 (m,
2 H, Ar), 3.85 (s, 3 H, CH3), 3.83 (s, 3 H, CH3), 1.57 (s, 9 H, 3CH3).
1H NMR (300 MHz, CDCl3): d = 8.10 (s, 1 H, Ar), 7.50 (d, J = 8.7
Hz, 1 H, Ar), 7.45 (d, J = 8.7 Hz, 1 H, Ar), 7.32–7.43 (m, 3 H, Ar),
7.17 (d, J = 7.2 Hz, 1 H, Ar), 4.01 (s, 3 H, CH3), 3.99 (s, 3 H, CH3),
2.41 (s, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 157.5, 155.8, 149.0, 142.0, 138.7,
137.8, 128.6, 128.5, 126.7, 124.7, 123.2, 123.1, 118.3, 116.4, 61.9,
56.5, 21.4.
13C NMR (75 MHz, CDCl3): d = 158.2, 154.9, 148.1, 134.8, 129.0,
128.2, 122.0, 118.0, 61.7, 56.5, 31.6, 28.4.
MS: m/z (%) = 262 (22) [M+], 207 (35), 191 (100), 177 (54), 160
(37), 149 (44), 89 (54).
MS: m/z (%) = 296 (64) [M+], 281 (100), 265 (16), 249 (20), 237
(18), 207 (39), 91 (41), 77 (20).
Acknowledgment
7,8-Dimethoxy-2-methyl-1(2H)-phthalazinone (Table 3, Entry
4)
The financial support provided by the University of Massachusetts
Boston is gratefully acknowledged.
Yellow crystals; mp 131–133 °C (CH2Cl2–MeOH, 99:1).
1H NMR (300 MHz, CDCl3): d = 7.97 (s, 1 H, Ar), 7.45 (d, J = 8.7
Hz, 1 H, Ar), 7.42 (d, J = 8.7 Hz, 1 H, Ar), 4.01 (s, 3 H, CH3), 3.99
(s, 3 H, CH3), 3.80 (s, 3 H, CH3).
References
13C NMR (75 MHz, CDCl3): d = 158.0, 155.4, 137.0, 130.9, 128.8,
125.1, 122.9, 118.0, 61.9, 56.5, 39.4.
MS: m/z (%) = 220 (55) [M+], 205 (100), 191 (67), 177 (45), 160
(42), 146 (42), 119 (46), 77 (50).
(1) (a) Gilchrist, T. L. Heterocyclic Chemistry, 3rd ed.;
Longman: NJ, 1997. (b) Török, M.; Jakab, G.; Bérczi, A.;
Dux, L.; Horváth, L. I. Biochim. Biophys. Acta 1997, 1326,
193. (c) Horváth, L. I.; Török, M.; Hideg, K.; Dux, L. J. Mol.
Recog. 1997, 10, 188. (d) Gilchrist, T. A. J. Chem. Soc.,
Perkin Trans. 1 1998, 615. (e) Nobuyoshi, A.; Akihiko, O.;
Chikara, M.; Tatsuya, T.; Masami, O.; Hiromitsu, S. J. Med.
Chem. 1999, 42, 2946. (f) Kohling, P.; Schmidt, A. M.;
Eilbracht, P. Org. Lett. 2003, 5, 3213. (g) Caron, S.;
Vazquez, E. J. Org. Chem. 2003, 68, 4104. (h) Bringmann,
G.; Tasler, S.; Endress, H.; Muhlbacher, J. Chem. Commun.
2001, 761. (i) Baran, P. S.; Richter, J. M.; Lin, D. W. Angew.
Chem. Int. Ed. 2005, 44, 609. (j) Török, B.; Abid, M.;
London, G.; Esquibel, J.; Török, M.; Mhadgut, S. C.; Yan,
P.; Prakash, G. K. S. Angew. Chem. Int. Ed. 2005, 44, 3086.
(k) Török, M.; Abid, M.; Mhadgut, S. C.; Török, B.
Biochemistry 2006, 45, 5377.
7,8-Dimethoxy-2-(2-methoxyphenyl)-1(2H)-phthalazinone
(Table 3, Entry 5)
Orange crystals; mp 140–142 °C (CH2Cl2–MeOH, 99:1).
1H NMR (300 MHz, CDCl3): d = 8.06 (s, 1 H, Ar), 7.34–7.48 (m,
4 H, Ar), 7.00–7.07 (m, 2 H, Ar), 3.97 (s, 3 H, CH3), 3.96 (s, 3 H,
CH3), 3.78 (s, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 157.3, 155.7, 154.7, 148.9, 137.7,
131.0, 129.9, 128.8, 125.0, 123.1, 122.7, 120.8, 118.2, 112.1, 61.9,
56.5, 55.8.
MS: m/z (%) = 312 (22) [M+], 297 (40), 281 (70), 265 (18), 204 (25),
174 (24), 120 (82), 78 (100).
Synthesis 2009, No. 11, 1801–1806 © Thieme Stuttgart · New York