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 isequipped with a magnetic stirring bar, a thermometer, and a three-waystopcock fitted with a drying tube containinganhydrous 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, andcooled in an ice bath. To the cooled mixture isslowly added 5.23 mL (0.06 mol) of oxalyl chloride by means of a syringe. The addition isaccompanied by gas evolution and formation of a white precipitate. The reactionmixture is stirred for an additional hour at 0°C. Excess oxalyl chlorideand solvent are removed under reduced pressure by first using a water aspirator and then a rotarypump at room temperature through the drying tube. The white solidremaining in the flask is N,N-dimethylchloromethylenammoniumchloride, which is used directly in Part B.

B. 6-Oxodecanal. The drying tube is removed and theflask is flushed with nitrogen. A nitrogen atmosphere is maintained throughout thesubsequent reaction. A dropping funnel is attachedand 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. Theflask is charged with 45 mL of acetonitrile  and 80 mL of tetrahydrofuran andcooled (methanol–liquid nitrogen)to −30°C. The contents ofthe funnel are added to the flask at −30°Cover 30 min. The reaction mixture is stirred at −30°C for an additional hour and at −20°C for 30 min. After the mixture iscooled to −90°C, 34 mL (0.046 mol) of a 1.35 M solution of lithium tri(tert-butoxy)aluminumhydride in tetrahydrofuran  is injected through the septum by means of asyringe over 30 min, while the internal temperature is kept below −85°C. Stirring is continued for anadditional 30 min at −90°C.To the flask is added 50 mL of 2 M hydrochloricacid solution, and the cooling bath is immediately removed. The organiclayer is separated and the aqueous layer is extracted with three 50-mL portions of ether. Thecombined organic extracts are washed with two 50-mLportions of saturated sodium hydrogen carbonatesolution and 50 mL of brine,dried over anhydrous sodium sulfate, and filtered.The solvent is removed with a rotary evaporatorand the residual liquid is distilled under reduced pressure to yield 5.78–6.35 g(85–93%) of 6-oxodecanalas 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。

5.1.3由羧酸合成酮

Preparation of Methyl(5-methoxy-2-nitrophenylacetyl)acetoacetate

A 2-L, three-necked, round-bottomedflask equipped with a magnetic stirring bar, inert gas inlet, and two stoppersis flame dried and cooled to room temperature under an atmosphere of argon. The flask is charged with 42.5 g(0.20 mol) of (5-methoxy-2-nitro-phenyl)-acetic acid in 480 mL ofanhydrous toluene. To the resulting suspension isadded 15.3 mL (0.21 mol) of thionyl chloridefollowed by 2 mL of anhydrous N,N-dimethylformamide(DMF). As soon as the DMF is added the color of the mixture turns light red.The mixture is stirred at room temperature overnight.  A 1-L, three-necked, round-bottomed flaskequipped with a magnetic stirring bar, 250-mL pressure-equalizing funnel, andan inert gas inlet is flame dried and allowed to cool to room temperature underargon. The flask is charged with 10.1 g(0.49 mol) of 97% sodium hydride in280 mL of dry tetrahydrofuran (THF) and thencooled to 0°C in anice bath. A solution of 45.3 mL (0.42 mol) of methylacetoacetate in 160 mL of dry THF is placed in the addition funneland added dropwise to the reaction flask over a period of 45–50 min. Afterthe addition is complete the light gray-colored solution is quickly transferredto a dried, 500-mL addition funnel. The funnel is mounted on the flaskcontaining the acid chloride solution. The solution of methylacetoacetate anion is added to the crude acid chloride solution over5 min and the resulting mixture is stirred overnight at room temperature.Water (350 mL) is added to the reaction mixture and the mixture is stirredfor 15 min before being poured into a 2-L separatory funnel. The layersare separated and the aqueous layer is extracted with ether(2 × 150 mL). The combined organic layers are washed with brineand dried over sodium sulfate. The filtered organiclayer is concentrated under reduced pressure and the residue is dissolved in100 mL of methanol. After cooling in thefreezer overnight, the yellow crystals that separate are collected and dried togive 34.8–37.3 g (56–60%) of methyl (5-methoxy-2- nitrophenylacetyl)acetoacetate,suitable for use in the next step.