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【结 构 式】 
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【分子编号】55219 【品名】1,4,5,8-tetrahydroxy-2,3-dihydro-9,10-anthracenedione 【CA登记号】 |
【 分 子 式 】C14H10O6 【 分 子 量 】274.2298 【元素组成】C 61.32% H 3.68% O 35.01% |
合成路线1
该中间体在本合成路线中的序号：(III)This compound has been obtained by two different methods: The reduction of 1,4-diamino-5,8-dihydroxyanthraquinone (I) or 1,5-diamino-4,8-dihydroxyanthraquinone (II) with Na2S2O4 and NaOH in water gives the leuco derivative (III), which is condensed with N,N-dimethylethylene-1,2-diamine (IV) in refluxing ethanol and reoxidized by air to yield 1,4-bis[2-(dimethylamino)ethylamino]-5,8-dihydroxyanthraquinone (V). Finally, this compound is treated with MCPBA in dichloromethane to afford the target bis-N-oxide. Alternatively, the reduction of tetrachlorophthalic anhydride (VI) with Zn and NaOH in water at 50-60 C gives 3,4,6-trichlorophthalic anhydride (VII), which is further reduced with Zn and NaOH in refluxing water to yield 3,6-dichlorophthalic anhydride (VIII). The reaction of (VIII) with KF and NaF at 260-27 ?C affords 3,6-difluorophthalic anhydride (IX), which is cyclized with hydroquinone (X) by means of AlCl3 and NaCl at 200 +/- 5 C to provide 1,4-difluoro-5,8-dihydroxyanthraquinone (XI). Finally, this compound is condensed with N,N-dimethylethylene-1,2-diamine (IV) in pyridine to afford the already reported 1,4-bis[2-(dimethylamino)ethylamino]-5,8-dihydroxyanthraquinone (V), which is oxidized with MCPBA as before.
| 【1】 Chang, P.; Chang, C.C.; An improved practical synthesis of leuco-1,4,5,8-tetrahydroxyanthraquinone. Synth. Commun. 1995, 25, 3, 1893. |
| 【2】 Denny, W.A.; Lee, H.H.; A large-scale synthesis of the bioreductive drug 1,4-bis[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione bis-N-oxide (AQ4N). J Chem Soc - Perkins Trans I 1999, 19, 2755. |
| 【3】 Patterson, L.H. (National Research Development Corp.); Anti-cancer cpds.. US 5132327; WO 9105824 . |
| 【4】 Denny, W.A.; Lee, H.H. (BTG International Ltd.); Process for the preparation of 1,4-bis[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione. WO 0005194 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 55217 | 1,4-diamino-5,8-dihydroxyanthra-9,10-quinone | C14H10N2O4 | 详情 | 详情 | |
| (II) | 55218 | 1,5-diamino-4,8-dihydroxyanthra-9,10-quinone | C14H10N2O4 | 详情 | 详情 | |
| (III) | 55219 | 1,4,5,8-tetrahydroxy-2,3-dihydro-9,10-anthracenedione | C14H10O6 | 详情 | 详情 | |
| (IV) | 14881 | N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine | 108-00-9 | C4H12N2 | 详情 | 详情 |
| (V) | 55220 | 1,4-bis{[2-(dimethylamino)ethyl]amino}-5,8-dihydroxyanthra-9,10-quinone | C22H28N4O4 | 详情 | 详情 | |
| (VI) | 51351 | Tetrachlorophthalic anhydride; 4,5,6,7-Tetrachloro-1,3-isobenzofurandione | 117-08-8 | C8Cl4O3 | 详情 | 详情 |
| (VII) | 55221 | 4,5,7-trichloro-2-benzofuran-1,3-dione | C8HCl3O3 | 详情 | 详情 | |
| (VIII) | 55222 | 3,6-Dichlorophthalic anhydride | C8H2Cl2O3 | 详情 | 详情 | |
| (IX) | 55223 | 3,6-Difluorophthalic anhydride | C8H2F2O3 | 详情 | 详情 | |
| (X) | 13163 | p-Dihydrobenzene; Hydroquinone | 123-31-9 | C6H6O2 | 详情 | 详情 |
| (XI) | 55224 | 1,4-difluoro-5,8-dihydroxyanthra-9,10-quinone | C14H6F2O4 | 详情 | 详情 |