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【结 构 式】 
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【分子编号】16845 【品名】2-methoxy-1,4-benzenediol 【CA登记号】824-46-4 |
【 分 子 式 】C7H8O3 【 分 子 量 】140.13872 【元素组成】C 60% H 5.75% O 34.25% |
合成路线1
该中间体在本合成路线中的序号：(I)As shown in Scheme 21591401a, the Pechmann reaction of 2-methoxy-hydroquinone (I) with 2-methyl-3-oxobutanoic acid ethyl ester (II) in 75% sulfuric acid gives 6-hydroxy-7-methoxy-3,4-dimethyl-2H-1-benzopyran-2-one (III), which is condensed with 1-(3-chloropropyl)-4-(2-methoxyphenyl)piperazin (IV) in the presence of K2CO3 and KI in ethanol yielding the target product as free base.
| 【1】 Noldner, M.; Hauer, H.; Chatterjee, S.S.; Anseculin Hydrochloride. Drugs Fut 1996, 21, 8, 779. |
| 【2】 Chatterjee, S.S.; Noldner, M.; Hauer, H. (Willmar Schwabe GmbH); Benzopyranones, a method for producing them and uses therefor. DE 4111861; JP 1994506922; US 5428038; WO 9218493 . |
| 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) | 16845 | 2-methoxy-1,4-benzenediol | 824-46-4 | C7H8O3 | 详情 | 详情 |
| (II) | 10362 | ethyl 2-methyl-3-oxobutanoate; ethyl 2-methylacetoacetate | 609-14-3 | C7H12O3 | 详情 | 详情 |
| (III) | 16847 | 6-hydroxy-7-methoxy-3,4-dimethyl-2H-chromen-2-one | C12H12O4 | 详情 | 详情 | |
| (IV) | 16848 | 1-(3-chloropropyl)-4-(2-methoxyphenyl)piperazine; 2-[4-(3-chloropropyl)piperazino]phenyl methyl ether | C14H21ClN2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)The reduction of 1,4-dihydroxy-9,10-anthraquinone (I) with NaBH4 in methanol gives 1,4-anthraquinone (II), which is reduced with Na2S2O4 in dioxane/water to yield 1,4-anthracenediol (III). The methylation of (III) with NaH and Me-I in DMF affords 1,4-dimethoxyanthracene (IV), which is condensed with 2-methoxy-1,4-benzoquinone (V) (obtained by oxidation of 2-methoxyhydroquinone (VI) with Ag2O and K2CO3 in benzene) by heating at 150 C with toluene in a sealed tube to provide the triptycene derivative (VII). The reaction of (VII) with KOH in dioxane/water gives the triptycenediol (VIII), which is oxidized with Ag2O in refluxing acetone to yield the triptycenequinone (IX). Finally, this compound is oxidized with Ce(NH4)2(NO3)6 to afford the target triptycenediquinone.
| 【1】 Hua, D.H.; Perchellet, J.-P. (Kansas State University); Triptycene analogs. WO 0228808 . |
| 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) | 53467 | 1,4-Dihydroxy-9,10-anthracenedione; 1,4-Dihydroxyanthraquinone; Chinizarin; Quinazarin; Quinizarin | 81-64-1 | C14H8O4 | 详情 | 详情 |
| (II) | 53468 | 1,4-Anthracenedione; 1,4-Anthraquinone | 635-12-1 | C14H8O2 | 详情 | 详情 |
| (III) | 53469 | 1,4-anthracenediol | 7218-35-1 | C14H10O2 | 详情 | 详情 |
| (IV) | 53470 | 1,4-dimethoxyanthracene; 4-methoxy-1-anthryl methyl ether | 13076-29-4 | C16H14O2 | 详情 | 详情 |
| (V) | 53471 | Methoxybenzoquinone | 2880-58-2 | C7H6O3 | 详情 | 详情 |
| (VI) | 16845 | 2-methoxy-1,4-benzenediol | 824-46-4 | C7H8O3 | 详情 | 详情 |
| (VII) | 53472 | 4,10,13-trimethoxypentacyclo[6.6.6.0~2,7~.0~9,14~.0~15,20~]icosa-4,9,11,13,15,17,19-heptaene-3,6-dione | n/a | C23H20O5 | 详情 | 详情 |
| (VIII) | 53473 | 4,10,13-trimethoxypentacyclo[6.6.6.02,7.09,14.015,20]icosa-2,4,6,9,11,13,15,17,19-nonaene-3,6-diol | n/a | C23H20O5 | 详情 | 详情 |
| (IX) | 53474 | 4,10,13-trimethoxypentacyclo[6.6.6.02,7.09,14.015,20]icosa-2(7),4,9,11,13,15,17,19-octaene-3,6-dione | n/a | C23H18O5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VI)The reduction of 1,4-dihydroxy-9,10-anthraquinone (I) with NaBH4 in methanol gives 1,4-anthraquinone (II), which is reduced with Na2S2O4 in dioxane/water to yield 1,4-anthracenediol (III). The methylation of (III) with NaH and Me-I in DMF affords 1,4-dimethoxyanthracene (IV), which is condensed with 2-methoxy-1,4-benzoquinone (V) (obtained by oxidation of 2-methoxyhydroquinone (VI) with Ag2O and K2CO3 in benzene) by heating at 150 C with toluene in a sealed tube to provide the triptycene derivative (VII). The reaction of (VII) with KOH in dioxane/water gives the triptycenediol (VIII), which is oxidized with Ag2O in refluxing acetone to yield the triptycenequinone (IX). The bromination of (IX) with NBS in hot DMF affords the bromo derivative (X), which is finally oxidized with Ce(NH4)2(NO3)6 to afford the target triptycenediquinone.
| 【1】 Hua, D.H.; Perchellet, J.-P. (Kansas State University); Triptycene analogs. WO 0228808 . |
| 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) | 53467 | 1,4-Dihydroxy-9,10-anthracenedione; 1,4-Dihydroxyanthraquinone; Chinizarin; Quinazarin; Quinizarin | 81-64-1 | C14H8O4 | 详情 | 详情 |
| (II) | 53468 | 1,4-Anthracenedione; 1,4-Anthraquinone | 635-12-1 | C14H8O2 | 详情 | 详情 |
| (III) | 53469 | 1,4-anthracenediol | 7218-35-1 | C14H10O2 | 详情 | 详情 |
| (IV) | 53470 | 1,4-dimethoxyanthracene; 4-methoxy-1-anthryl methyl ether | 13076-29-4 | C16H14O2 | 详情 | 详情 |
| (V) | 53471 | Methoxybenzoquinone | 2880-58-2 | C7H6O3 | 详情 | 详情 |
| (VI) | 16845 | 2-methoxy-1,4-benzenediol | 824-46-4 | C7H8O3 | 详情 | 详情 |
| (VII) | 53472 | 4,10,13-trimethoxypentacyclo[6.6.6.0~2,7~.0~9,14~.0~15,20~]icosa-4,9,11,13,15,17,19-heptaene-3,6-dione | n/a | C23H20O5 | 详情 | 详情 |
| (VIII) | 53473 | 4,10,13-trimethoxypentacyclo[6.6.6.02,7.09,14.015,20]icosa-2,4,6,9,11,13,15,17,19-nonaene-3,6-diol | n/a | C23H20O5 | 详情 | 详情 |
| (IX) | 53474 | 4,10,13-trimethoxypentacyclo[6.6.6.02,7.09,14.015,20]icosa-2(7),4,9,11,13,15,17,19-octaene-3,6-dione | n/a | C23H18O5 | 详情 | 详情 |
| (X) | 53475 | 4-bromo-5,10,13-trimethoxypentacyclo[6.6.6.02,7.09,14.015,20]icosa-2(7),4,9,11,13,15,17,19-octaene-3,6-dione | n/a | C23H17BrO5 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(V)The Diels-Alder cycloaddition between 1,4-dimethoxyanthracene (IV) and methoxyhydroquinone (V) in the presence of Ag2O and ZnI2 yields the triptycene quinone (VI). This compound has also been obtained by stepwise oxidation of (V) to methoxybenzoquinone (VII) with Ag2O, followed by Diels-Alder condensation with 1,4-dimethoxyanthracene (IV) to produce adduct (VIII) as a mixture of two stereoisomers. After isomerization of ketones (VIII) with KOH, oxidation with Ag2O leads to quinone (VI). Mono-quinone (VI) is oxidized to the bis-quinone (IX) employing ceric ammonium nitrate. Then, regioselective bromination of (IX) with N-bromosuccinimide (NBS) furnishes bromoquinone (X). Alternatively, compound (XI) is obtained from the bromination of (VI) with NBS, followed by oxidation with ceric ammonium nitrate). When bis-quinone (X) in THF solution is treated with dimethylamine gas (containing small amounts of methylamine), the title compound is obtained a regioisomeric mixture of methylamino derivatives, along with the expected dimethylamino analogues, which are separated by column chromatography.
| 【1】 Hua, D.H.; et al.; Syntheses and bioactivities of substituted 9,10-dihydro-9,10[1,2]benzenoanthracene-1,4,5,8-tetrones. Unusual reactivities with amines. J Org Chem 2002, 67, 9, 2907. |
| 【2】 Hua, D.H.; Perchellet, J.-P. (Kansas State University); Triptycene analogs. WO 0228808 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 53470 | 1,4-dimethoxyanthracene; 4-methoxy-1-anthryl methyl ether | 13076-29-4 | C16H14O2 | 详情 | 详情 |
| (V) | 16845 | 2-methoxy-1,4-benzenediol | 824-46-4 | C7H8O3 | 详情 | 详情 |
| (VI) | 53474 | 4,10,13-trimethoxypentacyclo[6.6.6.02,7.09,14.015,20]icosa-2(7),4,9,11,13,15,17,19-octaene-3,6-dione | n/a | C23H18O5 | 详情 | 详情 |
| (VII) | 53471 | Methoxybenzoquinone | 2880-58-2 | C7H6O3 | 详情 | 详情 |
| (VIII) | 53472 | 4,10,13-trimethoxypentacyclo[6.6.6.0~2,7~.0~9,14~.0~15,20~]icosa-4,9,11,13,15,17,19-heptaene-3,6-dione | n/a | C23H20O5 | 详情 | 详情 |
| (IX) | 57853 | 4-methoxypentacyclo[6.6.6.0~2,7~.0~9,14~.0~15,20~]icosa-2(7),4,9(14),11,15,17,19-heptaene-3,6,10,13-tetrone | C21H12O5 | 详情 | 详情 | |
| (X) | 57854 | 4-bromo-5-methoxypentacyclo[6.6.6.0~2,7~.0~9,14~.0~15,20~]icosa-2(7),4,9(14),11,15,17,19-heptaene-3,6,10,13-tetrone | C21H11BrO5 | 详情 | 详情 |