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【结 构 式】 
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【分子编号】11658 【品名】3,4-Dihydroxybenzoic acid 【CA登记号】99-50-3 |
【 分 子 式 】C7H6O4 【 分 子 量 】154.12224 【元素组成】C 54.55% H 3.92% O 41.52% |
合成路线1
该中间体在本合成路线中的序号：(I)The esterification of 3,4-dihydroxybenzoic acid (I) with refluxing methanol - H2SO4 gives the corresponding methyl ester (II), which is then treated with hydroxylamine in water containing NaOH.
| 【1】 Van't Riet, B.; Elford, H.L.; Wampler, G.L. (Molecules for Health, Inc.); Hydroxy benzohydroxamic acids and benzamides. US 4263322 . |
| 【2】 Prous, J.; Castaner, J.; DIDOX. Drugs Fut 1990, 15, 1, 22. |
| 【3】 Van't Riet, B.; Wampler, G.L.; Elford, H.W.; Synthesis of hydroxy- and amino-substituted benzohydroxamic acids: Inhibition of ribonucleotide reductase and antitumor activity. J Med Chem 1979, 22, 5, 589-92. |
合成路线2
该中间体在本合成路线中的序号：(I)The synthesis of amidox starting from 3,4-dihydroxybenzoic acid (I) is outlined: The first reaction is between the carboxylic acid (I) and thionyl chloride in ethyl acetate as a solvent under reflux conditions for 24 hours. After removal of excess thionyl chloride by evaporation, the residue is dissolved in ethyl acetate and added to aqueous ammonia under cooling. Excess of ammonia is evaporated. Acidification with hydrochloric acid to pH = 4.5 causes 3,4-dihydroxybenzamide (II) to precipitate. The amide is dried and treated with thionyl chloride in ethyl acetate under reflux overnight. The solvent is removed and the residue is heated in water to 95 C until the evolution of sulfur dioxide ceases. On cooling, 4-cyanocatechol (III) precipitates. It is recrystallized from water after charcoal treatment. An aqueous solution of hydroxylamine is prepared from hydroxylamine sulfate and sodium hydroxide. To this solution a small quantity of sodium sulfite is added with (III) and the solution is heated at 45 C overnight. The solution should not be in direct contact with air under alkaline conditions. The free base of amidox precipitates. It is filtered off, washed with water, then dissolved in dilute hydrochloric acid (pH = 1.5). After charcoal treatment and filtration, the solution is evaporated under reduced pressure. The dry residue is dissolved in a small volume of methanol. After addition of ethyl acetate, no precipitate is formed, but on heating pure amidox precipitates.
