【摘要】 本文报告脱二甲胺地霉红(Ⅰ)合成工作中两种有用中间体4-甲基-8-甲氧基萘酚-[1](Ⅵ)和1,8-二甲氧基-4-甲基萘甲酸-[2](Ⅶ)的合成以及其结构的证明。 4-甲基-8-甲氧基萘酚-[1](Ⅳ)可从两条途径合成:其一由8-甲氧基萘酚-[1](Ⅱ)经Gattermann醛合成及黄鸣龙改良Kishner-Wolff还原法而得。另一途径由2-氯-5-甲氧基苯甲酰氯(Ⅷ)经八步反应,首先获得4-甲基-5-氯-8-甲氧基四氢萘酮-[1](ⅩⅥ),其中每步反应都分离得到纯粹的产物。将ⅩⅥ经溴化,脱溴化氢及氢解反应便生成化合物(Ⅳ)。从这两途径所得的最后产物(Ⅳ)性质完全相同。 1,8-二甲氧基-4-甲基萘甲酸-[2](Ⅶ)乃由化合物Ⅳ引入溴原子,甲基化后,经金属-卤素的交换及羧基化而得。Ⅶ的结构证明如下;化合物(ⅩⅥ)经二溴化及脱溴化氢、甲基化后,生成1,8-二甲氧基-2-溴-4-甲基-5-氯萘(ⅩⅩ),另一方面,将Ⅵ氯化以期获得ⅩⅩ,却得到2,4-二氯-5-甲基-7-溴-8-甲氧基萘酚-[1](ⅩⅪ)。由于将ⅩⅩ氯化亦得到ⅩⅪ,化合物Ⅵ中溴的位置得到证明,因此Ⅶ的结构也予以肯定。更多还原

【Abstract】 (1) Two useful intermediates for the synthesis of desdimethylaminoterrarubein（Ⅰ）, namely 4-methyl-8-methoxynaphthol-[1] （Ⅳ） and 1, 8-dimethoxy-4-methyl-2-naphthoic acid （Ⅶ） were prepared and their structures ascertained. （2） The synthesis of 4-methyl-8-methoxynaphthol-[1] （Ⅳ） was accomplishedby two different routes. One consists of three stages of reactions: 1, 8-naphthalenediolwas mothylated to give 8-methoxynaphthol-[1] （Ⅱ）, m. p. 55°, which was convertedinto 4-hydroxy-5-methexynaphthadehyde-[1] （Ⅲ）, m. p. 112.5--113°, by Gatter-mann aldehyde synthesis and （Ⅲ） was then reduced into the requisite compound（Ⅳ）, m. p. 75--76°, by Huang-Minlonmodified Woelff-Kishner reduction. Another route to the synthesis of Ⅳ consists of the following sequence ofreactions: 2-Chloro-5-aminobenzoic acid was diazotized in dilute acetic acid insteadof in dilute HCl or H₂SO₄ as reported in literature, giving 2-chloro-5-hydroxyben-zcic acid in satisfactory yield. Its methylether was converted into the correspondingchloride （Ⅷ）, b. p. 126--128°/5 mm. and m. p. 24--25°, which was caused tocondense with diazomethame to give the diazoketone （Ⅸ）, m .p. 46--47°. Ⅸ wasthen treated with HCl or HBr to form 2 chloro-5-methexyphenacyl chloride （Ⅹa）,m. p. 40° or the bromide （Ⅹb）, m. p. 14°, respectively. Either Ⅹa or ,Ⅹb was allowed to condense with diethyl sodiomalonaio giving, after hydrolysis of the resulting ester,2-chloro-5-methoxyphenacyl malonic acid （Ⅺ）, m. p. 170°, which, in turn, producedβ-（2-chloro-5-methoxybonzoyl）-propionic acid （Ⅻ）, m. p. 92--93°, by pyrolysis.γ-Hydroxy-γ-（2-chloro-5-methoxyphenyl）-valerolaetono （ⅩⅢ）, b. p. 133--134°/ca.0.03 mm, was obtained by treating Ⅻ with methyl magnesium bromide. It affordedan unsaturated ester （ⅩⅠⅤ）, b. p. 120°/ca. 0.02mm, by successive treatment withthionyl chloride, ethanol and finally by pyrolysis. Hydrogenation in the presenceof Adams’ catalyst followed by hydrolysis converted ⅩⅠⅤ into γ-（2-chloro-5-methoxyphenyl）-valeric acid （ⅩⅤ）, m. p. 82-83°, the chloride of which was cyelizedto 4-mothyl-5-chloro-8-methoxyletralone-[1] （ⅩⅤⅠ）, m. p. 76--77°. Bromination ofⅩⅤⅠ witb one mole of bromine gave 2-bromo-4-methyl-5-chloro-methoxytetralone-[1] （ⅩⅤⅡ）, m. p. 85--86°. Dehydrobromination of ⅩⅤⅡ was effected readily byheating with morpholine on water--bath for 3 minutes giving 4-methyl-5-chloro-8-methoxynaphthol-[1] （ⅩⅤⅢ）, m. p. 122--123°. Finally it was converted intoⅣ by hydrogenolysis in the plesence of Pd-SrCO₃ catalyst. The behaviors of the final product （Ⅳ） obtained by two different routes wereshown to be identical in all respects. （3） 1, 8 Dimethoxy-4-methy-2-Inaphthoic acid was synthesised by the followingreactions: Ⅳ was first brominated to form 2-bromo-4-methyl-8-methoxynaphthol-[1] （Ⅴ）, m. p. 104--105.5°, which was then methylated, giving 2-bromo-4-mothyl-1, 8-dimethoxynaphthalene （Ⅵ）, m. p. 44--46°. Successive treatmentwith n-butyl lithium and carbon dioxide converted Ⅵ into Ⅶ, m. p. 121--122.5°. The structure of Ⅶ was proved as follows: Bromination of ⅩⅤⅠ with twomoles of bromine afforded 2, 2-dibromo-4-methyl-5-chloro-8-methoxytetralonel-[1]（ⅪⅩ）, m. p. 129--130°. It was converted into 1, 8-dimethoxy-2-bromo-4-methyl--chlcro-naphthalene （ⅩⅩ）, m. p. 87--88°, when treated with sodium methoxide andlimethyl sulfate simultaneously. On the other hand, chlorination of Ⅵ, produced2, 4-dichloro-5-methyl-7-bromo-8-mothoxynaphthol--[1] （ⅩⅩⅩⅠ）, m. p. 156--157°nstead of tine expected ⅩⅩ. Since ⅩⅩⅠ could also be obtained by chlorination ofⅩⅩ, the position of bromine in Ⅵ was thus demonstrates and therefore the strua-ature of Ⅷ ascertained.更多还原