经典合成反应标准操作— 醛酮的合成 药明康德新药开发有限公司

Reference: J. Am. Chem. Soc. 1959, 4113

3.1.2用硝基化合物氧化（Hass反应）

将卤甲基化合物与硝基烷烃的钠盐反应，可得相应的醛。

25-80oCArCH2X + (CH3)2C=NO2-Na+ ArCH2ON=C(CH3)2 ArCHOabs. EtOH70-80%OAr = C6H5, C6H4CH3, C6H4COCH3, C6H4COOCH3, C6H4CF3, C6H4CN, C6H4Br X = Cl, Br, I

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3.1.3用乌洛托品氧化（Sommelet反应）

将卤甲基化合物与乌洛托品（六甲基四胺，HMT）反应，然后用酸水解可得相应的醛。这是将芳香族甲基变成醛的一个有效方法。

M. Sommelet, Compt. Rend. 157, 852 (1913); Bull. Soc. Chim. France [4] 23, 95 (1918). Early reviews: S. J. Angyal, Org. React. 8, 197-217 (1954); Bayer, Houben-Weyl 7/1, 194 (1954). Synthetic applications: S. Miyano et al., Bull. Chem. Soc. Japan 59, 3285 (1986); D. Evans et al., Heterocycles 26, 1569 (1987).

3.1.3用乌洛托品氧化（Sommelet反应）反应示例：

A. 2-Thienylmethylhexamethylenetetrammonium chloride. In a 1-l. round-bottomed flask are placed 67 g. (0.5 mole) of 2-chloromethylthiophene, 400 mL. of chloroform, and 70 g. (0.5 mole) of hexamethylenetetramine. The flask is fitted with a reflux condenser, and the mixture is boiled gently for 30 minutes. The mixture is cooled, and filtered on a Büchner funnel. The precipitate is washed with 100 mL. of cold chloroform, drained thoroughly, and air-dried. The yield is 128–136 g. (94–99%) of a white powder.

B. 2-Thiophenealdehyde. The hexamethylenetetrammonium salt is placed in a 2-l. round-bottomed flask containing 400 mL. of warm water. The flask is fitted for steam

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distillation, and steam is passed in until all the aldehyde has distilled. The distillate is cooled, 10 mL. of 6 N acetic acid is added, and the aldehyde is extracted with two 100-mL. portions of ether. The ether solution is dried over anhydrous calcium chloride, and the ether is evaporated on a steam bath until the volume of the solution has decreased to about 50 mL. The solution is placed in a 100-mL. Claisen flask, the ether is removed by distillation, and the aldehyde distilling at 89–91°/21 mm., n25D 1.5880, is collected. The yield is 27–30 g. (48–53%) of a colorless oily liquid which darkens slowly on standing. Reference: Organic Syntheses, CV 3, 811

3.1.4用对亚硝基二甲苯胺氧化吡啶翁盐氧化（Kr?hnke反应） F. Kr?hnke et al., Ber. 69, 2006 (1936); 71, 2583 (1938); 72, 440 (1939).

A. A. Goldberg, H. A. Walker, J. Chem. Soc. 1954, 2540; F. Kr?hnke, Angew. Chem. Int. Ed. 2, 380 (1963); A. Markovac et al., Heterocyclic Chem. 14, 19 (1977); I. Maeba et al., J. Chem. Soc. Perkin Trans. I 1991, 939; S. N. Kilenyi, Comp. Org. Syn. 7, 657-659 (1991).

3.1.5用胺氧化物氧化

胺氧化物与卤化氧化物盐，将该盐用碱处理或热分解变可得醛。

ONCH2Br+CH2ON+NaOH95%CHO

3.2 由二卤甲基或二卤亚甲基合成醛酮

将二卤甲基或二卤亚甲基化合物在酸性或碱性条件下水解，则生成相应的醛酮。比如9，9-二溴芴在醋酸中，于醋酸钠存在下加热回流即可以良好的收率生成芴酮。

NaOAc/HOAc refluxBrBr90%O

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3.2.1 由二卤甲基合成醛反应示例：

Cl2, PCl5, light, heatClClCHCl2H2SO4, H2OClCHO

p-Clorobenzal cloride was added to a 4-l. wide-mouthed bottle containing 400 cc. of concentrated sulfuric acid, and stirred vigorously (Hood) for five hours. The viscous mixture is then transferred to a separatory funnel and allowed to stand overnight, after which the lower layer is run slowly, with stirring, into a 3-l. beaker three-quarters filled with cracked ice. The cream-colored solid obtained when the ice has melted is filtered by suction, washed with water, pressed dry on the funnel, and divided into three equal parts. Each portion is dissolved in a minimum of ether, and the ether solution is repeatedly shaken with 2 per cent sodium hydroxide solution until acidification of the washings gives no precipitate of p-chlorobenzoic acid. After removal of the ether by distillation on a steam bath, the residue is distilled under diminished pressure from a Claisen flask. The yield of p-chlorobenzaldehyde distilling at 108–111°/25 mm. and melting at 46–47° is 76–84 g. (54–60 per cent of the theoretical amount).

Reference: Organic Syntheses, Coll. Vol. 2, p.133; Vol. 12, p.12

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