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
6,7-Dichloro-5-methoxy-2,3-dihydro-1H-inden-1-one.
4,5-Dichloro-6-methoxy-2,3-dihydro-1H-indene (21 g, 0.097 mole) is dissolved in acetic acid (280 mL) and chromium trioxide (14 g, 0.14 mol) in a mixture of water (15 mL) and acetic acid (40 mL) is added dropwise with stirring over a period of one hour.. The mixture is poured, with stirring into cold water (1200 mL) and the solid that separates is removed by filtration, washed with water and dried. The product is subjected to column chromatographic separation using 225 g of silica gel and chloroform is used for elution. Evaporation of the solvent gives 6,7-dichloro-5-methoxy- 2,3-dihydro-1H- inden-1-one, 5.2 g, m.p. 154-156 oC Reference:US4316043
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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
4.4用高锰酸盐氧化合成酮
使用高锰酸钾，在温和的条件下，能合成酮。
OKMnO4, H2ON 70-80oCN
4.5 用醌氧化合成酮
用2，3-二氯-5，6-二氰基对苯醌（DDQ）氧化富电子的芳环苄位，能生成酮。
ODDQ (2 eq)NHEthanol83%NH
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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
5．由羧酸及其衍生物合成醛酮 5.1由羧酸合成醛 5.1.1用金属氢化物还原
一般不用金属氢化物直接部分还原羧酸得醛，而是先将羧酸还原至醇后再氧化比较可靠。但化学家也开发出了一些比较有用的直接还原方法，如用有机硼氢化物2，3-二甲基-2-丁基甲硼烷、1，1，2-三甲基丙基卤代甲硼烷、9-BBN及叔丁基锂等还原羧酸为醛。这些方法用于脂肪羧酸还原时非常有效。对于含有氨基、硝基及卤素等取代基的芳族羧酸，也可得到很高的收率。
虽然有报道用氢化二异丁基铝（DIBAL）在低温下还原羧酸可得到醛，但并不适用于合成。但氢化氨基铝是一种很好的羧酸还原试剂，可高收率地得到醛。氢化氨基铝可由LAH与N-甲基哌嗪制取。
5.1.1用金属氢化物还原羧酸为醛示例：
A.
N,N-Dimethylchloromethylenammonium
chloride.
A
500-mL,
three-necked,
round-bottomed flask is equipped with a magnetic stirring bar, a thermometer, and a three-way stopcock fitted with a drying tube containing anhydrous calcium chloride and a rubber septum. The flask is charged with 50 mL of dichloromethane and 3.07 (0.042 mol) of N,N-dimethylformamide added through the septum from a syringe, and cooled in an ice bath. To the cooled mixture is slowly added 5.23 mL (0.06 mol) of oxalyl chloride by means of a syringe. The addition is accompanied by gas evolution and formation of a white precipitate. The reaction mixture is stirred for an additional hour at 0°C. Excess oxalyl chloride and solvent are removed under reduced pressure by first using a water aspirator and then a rotary pump at room temperature through the drying tube. The white solid remaining in the flask is N,N-dimethylchloromethylenammonium chloride, which is used directly in Part B.
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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
B. 6-Oxodecanal. The drying tube is removed and the flask is flushed with nitrogen. A nitrogen atmosphere is maintained throughout the subsequent reaction. A dropping funnel is attached and charged with 7.45 g (0.04 mol) of 6-oxodecanoic acid, 3.32 g of pyridine, and 80 mL of tetrahydrofuran, which are mixed well by shaking. The flask is charged with 45 mL of acetonitrile and 80 mL of tetrahydrofuran and cooled (methanol–liquid nitrogen) to ?30°C. The contents of the funnel are added to the flask at ?30°C over 30 min. The reaction mixture is stirred at ?30°C for an additional hour and at ?20°C for 30 min. After the mixture is cooled to ?90°C, 34 mL (0.046 mol) of a 1.35 M solution of lithium tri(tert-butoxy)aluminum hydride in tetrahydrofuran is injected through the septum by means of a syringe over 30 min, while the internal temperature is kept below ?85°C. Stirring is continued for an additional 30 min at ?90°C. To the flask is added 50 mL of 2 M hydrochloric acid solution, and the cooling bath is immediately removed. The organic layer is separated and the aqueous layer is extracted with three 50-mL portions of ether. The combined organic extracts are washed with two 50-mL portions of saturated sodium hydrogen carbonate solution and 50 mL of brine, dried over anhydrous sodium sulfate, and filtered. The solvent is removed with a rotary evaporator and the residual liquid is distilled under reduced pressure to yield 5.78–6.35 g (85–93%) of 6-oxodecanal as a fragrant liquid, bp 85–90°C (1.4 mm). Reference: Organic Syntheses, Coll. Vol. 8, p.498; Vol. 66, p.121
5.1.2由脱CO2合成醛
α-酮酸及α，β-环氧酸（缩水甘油酸）加热时易脱羧成醛。如为α-酮酸，则加入苯胺或吗啉，脱羧后以亚胺或烯胺形式存在，难发生副反应。反应停止后用酸处理即可高收率的得到醛。
ORCOOHOH+BenzeneNRCOOH-CO2RNOH+84-100%RO
5.1.3由羧酸合成酮
Preparation of Methyl (5-methoxy-2-nitrophenylacetyl)acetoacetate
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