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
2.2 用活性MnO2氧化
活性MnO2广泛用于氧化α,β-不饱和基团（三键，双键、芳香环）的醇，可选择性氧化烯丙式醇，条件温和，不会引起双键的异构化MnO2的活性及溶剂的选择对反应至关重要，常用的溶剂有二氯甲烷、乙醚、石油醚、己烷、丙酮等。
2.2.1 用活性MnO2氧化示例一:
TBSOOHMnO2, CH2Cl2TBSOO
A 500-mL, round-bottomed flask, equipped with a Teflon-coated magnetic stirring bar, is charged with the 11.2 g of allylic alcohol and 300 mL of dichloromethane, and the resulting vigorously stirred solution is treated with 33 g of active manganese dioxide (380 mmol). Additional 2–5 g lots of the oxidant are added every 2–3 hr until the reaction is complete. The reaction mixture is vacuum-filtered through a pad of diatomaceous earth, and the pad is washed with 200 mL of dichloromethane. The resulting clear filtrate is concentrated carefully using a rotary evaporator, and the residual oil is purified by bulb-to-bulb distillation at 0.3 mm (pot temperature 100 °C) affording 8.43–8.71 g (87–90%) of enone as a pale yellow oil that solidifies when cooled below 15°C. Crystallization of the crude product from pentane at ?70 °C gives (4S)-(?)-tert-butyldimethylsiloxy-2-cyclopenten-1-one as colorless needles having mp 32–33 °C, [α]D23 ?65.1° (CH3OH, c 0.94). Reference: Organic Syntheses, Coll. Vol. 9, p.136; Vol. 73, p.44
2.2.2 用活性MnO2氧化示例二:
HOMnO2NNO A 100-mL, one-necked, round-bottomed flask is fitted with an efficient reflux condenser and arranged for magnetic stirring and heating. The flask is charged with 50 mL of pentane and 2.0 g (13 mmol) of alcohol. To the rapidly stirred solution is added 16 g (180 mmol) of activated manganese (IV) oxide in small portions over 5 min. The solution is heated at reflux for 18 hr and then an additional 8 g (90 mmol) of activated manganese (IV) oxide is added in
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portions. After being heated at reflux for 24 hr, the reaction mixture is filtered through a 2-cm Celite filter pad. The filtered manganese oxides are thoroughly washed with about 200–300 mL of dichloromethane. Evaporation of solvent from the combined filtrates leaves 1.4–1.6 g of a light yellow oil. Bulb-to-bulb distillation at 100°C/0.1 mm gives 1.27–1.40 g (8.4–9.3 mmol, 64–71% yield) of an oil 3-Butyroyl-1-methylpyrrole. Reference: Organic Syntheses, Coll. Vol. 7, p.102; Vol. 62, p.111
2.3用DMSO氧化
DMSO可由各种亲电试剂（E）活化后与醇反应，生成烷氧基硫盐，接着发生消除，生成醛或酮。
SO + ESOER1R2CHOHSOR1R2S+OR2 R1亲电试剂有DCC，(CH3CO)2O， (CF3CO)2O， SOCl2，(COCl)2等.
2.3.1 DMSO-(COCl)2氧化（Swern Oxidation）
Reference: K. Omura, D. Swern, Tetrahedron 34, 1651 (1978).
Reactivity/selectivity studies: M. Marx, T. T. Tidwell, J. Org. Chem. 49, 788 (1984). Reviews: A. J. Mancuso, D. Swern, Synthesis 1981, 165-185 passim; T. T. Tidwell, Org. React. 39, 297-572 passim (1990).
各种酰氯及亚硫酰氯作为DMSO的活化剂是有效的，而由草酰氯活化的DMSO对醇的氧化最为合适。
2.3.1.1 DMSO-(COCl)2氧化示例
BocOHDMSO, (COCl)2i-Pr2NEtOBocNCHO
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A 250-mL, three-necked, round-bottomed flask, containing a magnetic stirring bar is equipped with a low-temperature thermometer and two equalizing dropping funnels. One of these is connected to a nitrogen flow line and is charged with a solution of N-Boc-L-serinol (8.0 g, 34.6 mmol) in methylene chloride (60 mL), the other is charged with a solution of dimethyl sulfoxide (8.10 g, 103.71 mmol) in 10 mL of dried methylene chloride. The flask is charged with a solution of oxalyl chloride (6.58 g, 51.9 mmol) in 80 mL of methylene chloride, then cooled to ?78°C in a CryoCool bath. When the solution in the flask is at ?78°C, dimethyl sulfoxide is added dropwise over 25 min, while the temperature of the reaction mixture rises to ?70°C. At the end of the addition the reaction solution is warmed to ?60°C over a period of 20 min, then the N-Boc-L-serinol is added dropwise over 50 min and the reaction temperature rises to ?55°C. The dropping funnel is washed with two 5-mL portions of methylene chloride, then charged with a solution of N,N-diisopropylethylamine (36 mL, 200 mmol) in 5 mL of methylene chloride and the reaction solution is warmed to ?45°C over a period of 30 min. N,N-Diisopropylethylamine is added over 5 min, then the reaction flask is removed from the CryoCool bath and allowed to warm to 0°C over 10 min. The reaction solution is transferred to a 500-mL separatory funnel charged with 130 mL of ice-cold 1 M hydrochloric acid solution. The two phases are separated, the aqueous phase is extracted with methylene chloride (3 × 30 mL), and the combined organic phases are washed with pH 7 aqueous phosphate buffer (4 × 80 mL), then dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 7.89 g (99% crude yield) of the aldehyde as a clear yellow oil. Analysis of crude aldehyde by 1H NMR indicates a chemical purity of > 95%.
Reference: Organic Syntheses, Coll. Vol. 10, p.320; Vol. 77, p.64
2.3.2 DMSO-SO3-Pyridine
在常温条件下，DMSO 和 SO3-pyridine 混合，和有机碱（如三乙胺和吡啶）反应生成的中间体可以快速氧化伯醇和仲醇生成醛或酮，且收率较高。可有效的氧化烯丙醇类化合物为 a , ?-不饱和羰基化合物。还可以用来氧化生物碱类的醇化合物为酮类化合物。DMSO-SO3-pyridine试剂还用来氧化部分乙酰化的糖类化合物，得到新的不饱和的糖类化合物。
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Preparation of 1,2,3,4-tetramethoxy-5-methyl-6-(3-formylpropyl)-benzene
OOOOOHSO3.pyridine complexOOOOO
In anhydrous dimethyl sulfoxide (75 ml) were dissolved, 1,2,3,4-tetramethoxy-5-methyl-6- (4-hydroxybutyl)benzene (14.2 g, 50 mmole) and triethylamine (56.0 ml), and the solution was stirred at room temperature. A solution of sulfur trioxide pyridine complex (31.8 g, 200 mmole) in anhydrous dimethyl sulfoxide (75 ml) was added dropwise to the solution over a 25-minute period, followed by stirring at room temperature for 35 minutes. The reaction solution was poured into ice-water (300 g), and the product was extracted with isopropyl ether (500 ml). The isopropyl ether layer was washed with 10percent aqueous phosphoric acid solution and aqueous sodium chloride solution, successively, and dried (over MgSO4), and the solvent was distilled off. The residue was distilled under reduced pressure, thereby yielding 1,2,3,4-tetramethoxy-5-methyl-6-(3-formylpropyl)-benzene (11.3 g, 80%, bp 137 to 140oC 0.7mmHg). Reference: US4393075;
2.4 用氧铵盐氧化
用氧铵盐氧化醇即可得到相应的醛酮。
2.4.1 用氧铵盐氧化示例：
OHCH2Cl2, aq. NaOCl, pH 9.5KBr (cat.)0-15oCONO
A 1-L, three-necked, round-bottomed flask is fitted with a mechanical stirrer, pressure-equalizing dropping funnel, and a thermometer. The flask is charged with 44.05 g (0.50
mol)
of
(S)-(?)-2-methyl-1-butanol,
0.78
g
(5
mmol)
of
2,2,6,6-tetramethylpiperidin-1-oxyl, 170 mL of dichloromethane, and a solution of 5.95 g (0.050 mol) of potassium bromide in 25 mL of water. The reaction mixture is vigorously
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stirred and cooled to ?10°C with a salt–ice bath, then 550 mL (0.55 mol) of 1 M aqueous sodium hypochlorite at pH 9.5 is added over 15–20 min, keeping the temperature of the reaction mixture between 10 and 15°C. The mixture is stirred for a further 3 min. The orange organic phase is separated and the aqueous phase is extracted with 50 mL of dichloromethane. The combined organic extracts are washed with 100 mL of 10% aqueous hydrochloric acid containing 1.6 g (0.010 mol) of potassium iodide, 60 mL of 10% aqueous sodium thiosulfate, and 60 mL of water. The organic phase is dried over anhydrous magnesium sulfate and then distilled at atmospheric pressure through a 20-cm Vigreux distilling column to give 35.3–36.3 g (82–84%) of (S)-(+)-2-methylbutanal as a colorless oil, bp 90–92°C (GC purity >99%), [α]D22 +36.8° (acetone, c 2.5).
Reference: Organic Syntheses, Coll. Vol. 8, p.367; Vol. 69, p.212 2.5 用高价碘试剂氧化
高价碘氧化剂可以在中性或接近中性的条件下，在室温很温和的将伯醇和仲醇氧化为醛酮。一般用二氯甲烷作溶剂。
常用的高价碘氧化剂有三种，即 (Diacetoxyiodo)benzene (DIB)， o-iodoxybenzoic acid (IBX) 和Dess-Martin periodinane (DMP)。
DMP可由邻碘苯甲酸通过两步反应制得。(Dess, D. B.; Martin J.C., J. Org. Chem., 1983, 48, 4188)
ICOOHKBrO3H2SO4 93%OH-+IOOOAcOH, Ac2O 100 oC 93?OOAcIOAcOODMP
2.5 .1 Dess-Martin氧化反应示例：
OHDMPO
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