经典化学合成反应标准操作醛酮的合成

经典化学合成反应标准操作醛酮的经典合成
目录
1．前言 (4)
2．由醇合成醛酮 (4)
2.1铬（VI）试剂 (4)
2.1.1 Jones氧化（Cr2O3/H2SO4/acetone） (4)
2.1.2 Collins氧化（Cr2O3.2Py） (5)
2.1.3 PCC（Pyrindium Chlorochromate）氧化 (8)
2.1.4 PDC（Pyrindium Dichromate）氧化 (9)
2.2 用活性MnO2氧化 (10)
2.2.1 用活性MnO2氧化示例一: (10)
2.3用DMSO氧化 (11)
2.3.1 DMSO-(COCl)2氧化（Swern Oxidation） (11)
2.3.2 DMSO-SO3-Pyridine (12)
2.4 用氧铵盐氧化 (13)
2.4.1 用氧铵盐氧化示例： (13)
2.5 用高价碘试剂氧化 (14)
2.5 .1 Dess-Martin氧化反应示例： (14)
2.5.2 IBX氧化反应示例： (15)
2.6 亚硝酸钠和醋酐氧化 (15)
2.6.1 亚硝酸钠和醋酐氧化示例 (15)
2.6 TPAP-NMO 氧化 (16)
2.6.1 TPAP-NMO 氧化示例 (16)
2.7 1,2-二醇的氧化 (16)
2.7.1 1,2-二醇的氧化示例一： (17)
2.7.1 其他1,2-二醇的氧化相关文献： (18)
3．由卤化物合成醛酮 (18)
3.1 由伯卤甲基和仲卤甲基的氧化合成醛酮 (18)
3.1.1 用DMSO氧化（Kornblum反应） (18)
3.1.2用硝基化合物氧化（Hass反应） (20)
3.1.3用乌洛托品氧化（Sommelet反应） (21)
3.1.4用对亚硝基二甲苯胺氧化吡啶翁盐氧化（Kröhnke反应） (22)
3.1.5用胺氧化物氧化 (22)
3.2 由二卤甲基或二卤亚甲基合成醛酮 (23)
3.2.1 由二卤甲基合成醛反应示例： (23)
3.3 由有机金属化合物的酰化合成醛酮 (24)
3.3.1 由有机金属化合物的酰化合成醛酮示例 (25)
3.4 由Pd催化反应合成醛 (25)
4．由活泼甲基或活泼亚甲基烷烃合成醛酮 (25)
4.1 用SeO2氧化合成醛酮 (26)
4.1.1 用SeO2氧化合成醛酮示例 (26)
4.2用空气氧化合成酮 (26)
4.2.1用空气氧化合成酮反应示例： (27)
4.3 用铬酸氧化合成酮 (27)
4.3.1 用铬酸氧化合成酮示例 (27)
4.4用高锰酸盐氧化合成酮 (29)
4.5 用醌氧化合成酮 (29)
5．由羧酸及其衍生物合成醛酮 (30)
5.1由羧酸合成醛 (30)
5.1.1用金属氢化物还原 (30)
5.1.2由脱CO2合成醛 (31)
5.1.3由羧酸合成酮 (31)
5.2由酰氯及酸酐合成醛酮 (33)
5.2.1用Rosenmund法合成 (33)
5.2.2用金属氢化物还原 (34)
5.3由酯及内酯合成醛 (35)
5.3.1 酯通过DIBAL还原为醛示例： (36)
5.4由酰胺合成醛酮 (36)
5.4.1 由酰胺合成醛酮 (37)
5.4.2 McFadyen-Stevens Reaction (38)
5.5由酯或酰氯经Weinreb酰胺合成醛酮 (39)
5.5.1 由Weinreb酰胺还原合成醛反应示例一 (40)
5.5.2由Weinreb酰胺还原合成酮反应示例: (41)
5.6由氰合成醛酮 (41)
5.6.1DIBAL 还原腈到醛示例（最重要的方法） (42)
5.6.2Li(EtO)3AlH 还原腈到醛示例（较重要的方法） (43)
5.6.3Ranney Ni 加氢还原氰到合成醛示例 (43)
5.6.4有机金属试剂对腈加成合成酮示例 (44)
6. 由烯烃、芳环合成醛酮 (46)
6.1 由烯烃臭氧氧化合成醛 (46)
6.2 烯烃用OsO4/NaIO4氧化合成醛 (47)
6.3 烯烃经由有机硼化合物中间体的烯烃甲酰化合成醛 (47)
6.5 由烯烃的甲酰化合成醛 (48)
6.5.1 Vilsmeyer反应 (48)
6.5.2 Duff’s 甲酰化 (51)
6.5.3 Reimer-Tiemann 甲酰化 (52)
6.5.4 Gattermann甲酰化 (53)
6.5.5 多聚甲醛/甲醇镁苯酚甲酰化 (53)
6.5.6氯化锡/多聚甲醛苯酚甲酰化 (54)
6.5.7重氮化后甲酰化 (54)
6.6烯烃经加成-氧化反应合成酮 (56)
6.6.1 烯烃经加成-氧化反应合成酮示例 (56)
7. 由炔烃合成醛酮 (57)
7.1 由加成-氧化反应合成醛酮 (57)
7.2 由氧化反应合成酮 (57)
7.3 由加成-水解反应合成酮 (58)
7.4 由加成-还原反应合成酮 (59)
7.5 由加成-烷基化，酰化等反应合成酮 (59)
8. 由醚及环氧化合物合成醛酮 (59)
8.1 Claisen重排 (59)
8.2酸催化下环氧化物重排 (61)
8.2.1 酸催化下环氧化物重排合成醛酮示例一 (61)
8.3氧化法 (61)
8.4 水解法缩醛或酮合成醛酮 (61)
9. 由胺合成醛 (62)
9.1胺的氧化 (62)
9.1.1 胺的氧化合成醛反应示例： (63)
9.2 由胺经由西佛碱的方法 (64)
9.2.1 由胺经由西佛碱合成醛示例 (64)
9.3 自苯胺衍生物合成 (64)
10. 由硝基化合物合成醛酮 (64)
11. 由Friedel-Crafts反应合成芳基酮 (65)
11.1 由Friedel-Crafts反应合成芳基酮示例 (68)
12. Dieckmann 缩合脱酸 (69)
13. 由合成子合成醛酮 (71)
14. 由砜合成醛酮 (71)
15. Michael 反应和类似反应(Addition, Condensation) (71)
1．前言
醛和酮是一类重要的有机化合物，其合成在有机合成中占有非常重要的地位。

醛和酮的合成方法繁多，新合成途径也层出不穷。

本部分主要以官能团的转换为主线，依次讨论了由醇、卤化物，甲基、亚甲基、羧酸及其衍生物、烯烃、炔烃、醚及环氧化合物、胺、硝基化合物等转换为醛酮的一些非常实用的方法，一些少用或罕见的反应并没有收录进去。

2．由醇合成醛酮
由醇合成醛酮是有机合成中的一类非常重要的反应。

由伯醇的氧化可以得到醛。

由于醛处于醇与羧酸的中间氧化状态，就必须选择适当的氧化剂加以控制，不致氧化过度而生成羧酸。

由仲醇的氧化可以得到酮。

但仲醇过度氧化可以导致分子开裂。

由叔醇的氧化开裂、转位等反应也能合成酮，但实用范围不大。

由此可见，要讨论由醇的氧化就必须从所使用氧化剂氧化性的强弱、醇分子的结构以及反应条件等多个方面入手。

本部分由讨论最常用的铬（VI）氧化剂开始，依次讨论了活性MnO2，DMSO试剂，氧铵盐，高价碘化物等氧化剂在醇氧化合成醛酮反应中的应用。

2.1铬（VI）试剂
常用的铬（VI）试剂主要有三氧化铬（CrO3）、重铬酸、铬酸酯[CrO2(OCOR)2]、铬酰氯（CrO2Cl2）等。

为了控制醇不被过度氧化，化学家已经开发了种种氧化方法，最常用的方法有Jones氧化法（Cr2O3/H2SO4/acetone）、Collins氧化法（Cr2O3·2Py）、PCC （Pyrindium Chlorochromate）及PDC（Pyrindium Dichromate）氧化法等。

2.1.1 Jones氧化（Cr2O3/H2SO4/acetone）
Jones试剂通常可以将伯醇氧化成酸，把仲醇氧化成酮
2.1.1.1（Cr2O3/H2SO4/acetone）合成方法示例
A 1-L, round-bottomed flask equipped with a magnetic stirring bar and pressure-equalizing dropping funnel is charged with ethyl 3-hydroxy-4-pentenoate and 400 mL of acetone. The mixture is cooled in an ice bath and Jones reagent (175 mL) is added dropwise via the dropping funnel (addition time is approximately 30–40 min). When addition of the Jones reagent is complete, the reaction mixture is allowed to warm slowly to room temperature and is stirred overnight (10–20 hr). Methanol (20 mL) is added to quench excess Jones reagent and the reaction mixture is poured into a 2-L separatory funnel containing diethyl ether (800 mL). After thorough mixing, the layers are separated and the aqueous layer is extracted with diethyl ether (three 200-mL portions). The combined organic layers are washed with brine (two 200-mL portions), dried over MgSO4, filtered, and the solvent is removed by simple distillation. Final purification is accomplished by Kugelrohr distillation at 0.60 mm (oven temp 45°C) with a 250-mL receiving bulb cooled to −78°C using a dry ice/isopropyl alcohol cold bath. The purified product (14.9 g, 52%) can be stored at −20°C for several months without decomposition.
Notes：Jones reagent is prepared by dissolving chromium oxide (CrO3) (23.5 g) in con. sulfuric acid (21 mL) with cooling and then diluting with distilled water to give a total volume of 175 mL.
Reference: Organic Syntheses, Coll. Vol. 9, p.432; Vol. 71, p.236
2.1.2 Collins氧化（Cr2O3·2Py）
Collins氧化法是利用CrO3-pyridine配合物将伯醇和仲醇依次氧化成醛（和/或酸）和酮的方法。

（G. I. Poos, G. E. Arth, R. E. Beyler, L. H. Sarett, J. Am. Chem. Soc.75, 422 (1953).）
Collins氧化法是在Sarett氧化法（以吡啶为溶剂）基础上的改进，以二氯甲烷为溶剂氧化伯醇为醛（J. C. Collins, Tetrahedron Letters1968, 3363; J. C. Collins, W. W. Hess, Org. Syn.52, 5 (1972); R. W. Ratcliffe, ibid.55, 84 (1976).）.
2.1.2.1 Dipyridine chromium(VI) oxide的制备方法
A dry, 1-l., three-necked flask fitted with a sealed mechanical stirrer, a thermometer, and a drying tube, is charged with 500 ml. of anhydrous pyridine, which is stirred and cooled to approximately 15 °C with an ice bath. The drying tube is periodically removed and 68 g. (0.68 mole) of anhydrous chromium (VI) oxide is added in portions through the neck of the flask over a 30-minute period. The chromium trioxide should be added at such a rate that the temperature does not exceed 20 °C and in such a manner that the oxide mixes rapidly with the pyridine and does not adhere to the side of the flask. As the chromium trioxide is added, an intensely yellow, flocculent precipitate separates from the pyridine and the viscosity of the mixture increases. When the addition is complete, the mixture is allowed to warm slowly to room temperature with stirring. Within one hour the viscosity of the mixture decreases and the initially yellow product changes to a deep red, macrocrystalline form that settles to the bottom of the flask when stirring is discontinued. The supernatant pyridine is decanted from the complex and the crystals are washed several times by decantation with 250-ml. portions of anhydrous petroleum ether. The product is collected by filtration on a sintered glass funnel
and washed with anhydrous petroleum ether, avoiding contact with the atmosphere as much as possible. The complex is dried at 10 mm. until it is free-flowing, leaving 150–160 g. (85–91%) of dipyridine chromium (VI) oxide as red crystals. The product is extremely hygroscopic; contact with moisture converts it rapidly to the yellow dipyridinium dichromate. It is stored at 0° in a brown bottle.
Reference: Organic Syntheses, Coll. Vol. 6, p.644; Vol. 52, p.5
2.1.2.2 Collins氧化标准操作
A sufficient quantity of a 5% solution of dipyridine chromium (VI) oxide in anhydrous dichloromethane is prepared to provide a sixfold molar ratio of complex to alcohol, an excess usually required for complete oxidation to the aldehyde. The freshly prepared, pure complex dissolves completely in dichloromethane at 25 °C at 5% concentration, giving a deep red solution, but solutions usually contain small amounts of brown, insoluble material when prepared from crude complex. The alcohol, either pure or as a solution in anhydrous dichloromethane, is added to the red solution in one portion with stirring at room temperature or lower. The oxidation of unhindered primary (and secondary) alcohols proceeds to completion within 5 to 15 minutes at 25 °C with deposition of brownish-black, polymeric, reduced chromium–pyridine products. When deposition of reduced chromium compounds is complete (monitoring the reaction by GC or TLC is helpful), the supernatant liquid is decanted from the (usually tarry) precipitate, which is rinsed thoroughly with dichloromethane.
The combined dichloromethane solutions may be washed with dilute hydrochloric acid, sodium hydrogen carbonate solution, and water, or filtered directly through a filter aid, or passed through a chromatographic column to remove traces of pyridine and chromium salts. The product is obtained by removal of dichloromethane; any pyridine that remains can often be removed under reduced pressure.
2.1.3 PCC（Pyrindium Chlorochromate）氧化
PCC易于合成和保存，操作简单，是将伯醇和仲醇氧化成醛和酮的应用最广的氧化方法。

PCC中所用的碱除吡啶外，也可以是其它碱，且随着碱性部分碱性的增强，氧化的选择性也提高。

其中，DMAP·HCrO3Cl为适用于烯丙醇类及苄醇类的选择性氧化试剂。

OH HO
O
HO
DMAP, HCrO3Cl
PCC的氧化以均相反应为主，但有的方法是将催化剂吸附于硅胶、氧化铝等无机载体或离子交换树脂等有机高分子载体上，对醇作非均相催化氧化。

后处理简单并可控制反应的选择性。

2.1.
3.1 PCC氧化合成方法示例:
Preparation of 1,2:4,5-Di-O-isopropylidene-D-erythro-2,3-hexodiulo-2,6-pyranose
A 500-mL, round-bottomed flask equipped with a 4.5-cm, egg-shaped Teflon-coated magnetic stir bar is charged with 130 mL of CH2Cl2, the alcohol prepared in Step A (10.4 g, 40.0 mmol), and 15 g of freshly powdered 3 Å molecular sieves. Pyridinium chlorochromate (21.5 g, 100 mmol) is added portionwise over 10 min and the resulting mixture is stirred at room temperature for 15 hr. Ether (200 mL) is added slowly with vigorous stirring and the solution is filtered under vacuum through a pad of 35 g of Celite. The solids remaining in the reaction flask are transferred to the Celite pad by scraping with a spatula and washing with three 50-mL portions of ether. The resulting cloudy brown filtrate is concentrated by rotary evaporation at room temperature to give a brown solid. To this solid is added 25 mL of 1:1 ether:hexane and the solids are scraped with a spatula. The mixture is then poured onto 60 g of Whatman 60 Å (230-400 mesh) silica gel packed in a 4-cm diameter chromatography column and the liquid is adsorbed onto the silica gel by gravity. The material remaining in the
flask is further washed with 1:1 ether:hexane and transferred onto the silica gel; this process is repeated until all the material has been loaded onto the silica gel. The ketone is eluted using 500 mL of 1:1 ether:hexane and the eluent is concentrated by rotary evaporation to afford the crude ketone as a white solid. This material is dissolved in 40-45 mL of boiling hexane. Upon cooling the solution to room temperature, the ketone begins to crystallize. The flask is then cooled to −25 °C for 2 hr. The resulting solids are collected by filtration, washed with three 25-mL portions of cold (−25°C) hexane, and dried to afford 8.84-9.08 g, (86-88%) of the ketone as a white solid.
Notes：PCC is prepared by addition of pyridine to a solution of chromium trioxide (CrO3) in aqueous HCl and crystallization.
Reference:Organic Syntheses, Vol. 80, p.1
PCC的合成方法
100 g of Chromium trioxide (CrO3) was dissolved in 100 ml of water and 80.6 ml of pyridine was added (keep the temperature under 30 o C), followed by 400 ml of acetone. Reaction mixture was cooled to -20 o C and yellow crystall was collected and washed with acetone and dried to give 127.2 g of PCC. Yield: 68%.
2.1.4 PDC（Pyrindium Dichromate）氧化
PDC的氧化能力较PCC强，其氧化作用一般在中性条件下进行，而PCC则需在酸性中进行。

因此，对酸不稳定的化合物用PCC氧化时，必须在醋酸钠存在下进行。

PDC 的氧化一般在二氯甲烷中进行，如在DMF中进行时，氧化性增强，能将伯醇最终氧化成酸。

PDC的氧化操作基本和PCC相同，这里不再举例说明。

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:
MnO, CH Cl
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:
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
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。

S O + E S O E S O 2R 1
S O R 2R 1
+12 亲电试剂有DCC ，(CH 3CO)2O ， (CF 3CO)2O ， SOCl 2，(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 OH N O
Boc CHO N O Boc 2i-Pr 2NEt
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 , ß-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。

Preparation of 1,2,3,4-tetramethoxy-5-methyl-6-(3-formylpropyl)-benzene
O
O O
O
SO 3.pyridine complex O O O O O
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 140o C 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：
CH Cl , aq. NaOCl, pH 9.5N O KBr (cat.)
0-15o C
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
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)
I COOH
I+
O
O
OH
O-I
O
O
OAc
OAc
AcO
KBrO
3
24
93%
2
100 o C
93%
DMP
2.5 .1 Dess-Martin氧化反应示例：
O
To a solution of (Z)-hex-3-enol (9.55 g, 9.55 mmol) in CH2Cl2 (100 mL) under argon was added at 0 °C the DMP (4.85 g, 11.46 mmol). After 5 min, the reaction mixture was allowed to warm to r.t. and stirred for 1 h. The mixture was cooled down to 0 °C and washed with a satarate solution (80 mL) of NaHCO3/Na2S2O3 (1:1). After decantation the organic layer was washed once again (20 mL). The combined aqueous layers were extracted with CH2Cl2(30 mL). After drying over MgSO4for 2 min, the organic phase was concentrated by slow distillation of CH2Cl2at 760 mm Hg. Addition and distillation of anhydrous benzene allowed obtaining an anhydrous solution of hex-3-enal (Yield: 95%). Reference: Synthesis2002, No. 3, 326–330
2.5.2 IBX氧化反应示例：
O O O
IBX
DMSO
76%
General procedure oxidation of alcohols with IBX: A sample of 11 mmol of recrystallised IBX and 10 mmol of general alcohols were added to (27.5mL) DMSO to form 0.4 M of solution and this mixture was stirred at room temperature for 4 h. Water (20mL) was then added to the reaction mixture to precipitate 2-iodobenzoicacid crystals, and these crystals were decanted. The mother liquid was extracted with ether (3 x 25mL), washed with NaHCO3 solution, and dried over MgSO4 to obtain aldehydes or ketones.
Reference: Turk. J. Chem. 2003, 27, 713-716
2.6 亚硝酸钠和醋酐氧化
一个较实用的合成醛的方法，反应一般在室温下进行，反应时间较短，可氧化大部分伯醇、烯丙醇和苄醇，而且产率较高，副反应较少。

2.6.1 亚硝酸钠和醋酐氧化示例
O2N O2N O
NaNO2,Ac2O
A typical procedure for oxidation of 4-nitrobenzyl alcohol: a mixture of NaNO2(1035 mg, 15
mmol) and 4-nitrobenzyl alcohol (5 mmol) in acetic anhydride (2 mmol) was stirred. A spontaneous exothermic reaction took place which was controlled by cooling the mixture in ice. After completion of the reaction (TLC), the product was extracted with ether (2 × 10 ml). Removal of the solvent under reduced pressure a.orded crude 4-nitrobenzaldehyde which was further puri.ed by column chromatography (petroleum ether –ethyl acetate, 9 : 1). Reference: J. Chem. Soc ., Perkin Trans. 1, 2000, 3559–3560
2.6 TPAP-NMO 氧化
TPAP ([n-Pr 4N][RuO 4])是比较温和的将醇氧化为醛酮的方法(Reviews: Ley, Synthesis, 1994, 639)，反应为均相，收率较高，常用于对复杂分子的氧化。

OSi t BuMe 2OH
OSi t BuMe 2
OSi t BuMe 2O OSi t BuMe 2
2.6.1 TPAP-NMO 氧化示例
Tetrapropylammonium perruthenate (16 mg, 0.0468 mmol), N-methylmorpholine -N-oxide (0.16 g, 1.4 mmol), and 3Å molecular sieves (0.47 g) were added to a solution of alcohol (400 mg, 0.94 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 30 min then filtered through a Celite pad and the solvent evaporated in vacuo. Flash chromatography of the residue using 10% diethylether - hexane as eluent afforded 2,8-Bis(tert-butyldimethylsilyloxy) undec-10-en-6-yn-5-one (385 mg, 98%) as colorless oil. Reference:ARKIVOC 2001 (i) 74-87
2.7 1,2-二醇的氧化
氧化1,2-二醇的氧化剂一般为过碘酸及四醋酸铅。

用过碘酸氧化的反应虽然选择性好且有意义，但因氧化剂不溶于有机溶，应用受到了限制。

为了弥补这个缺点，可用相转移催化剂的双相体系氧化的改良法或使用硅胶的非均相反应，二者都很有效。

乙酸钴，硝酸铊也可氧化1,2-二醇类化合物。

2.7.1 1,2-二醇的氧化示例一：
NaIO4, NaHCO3
A large, magnetic stir bar is added to the flask that contains the crude solid diacetonide from procedure A above and 700–800 mL of dichloromethane (10 mL/g of diacetonide) is added. The flask is equipped with a condenser and heating mantle, and the slurry is stirred vigorously and heated to reflux until the solids are digested to an even consistency. The mantle is removed, the slurry is allowed to cool below reflux, and Celite (10 g) is added with stirring. The contents are further cooled to room temperature and vacuum-filtered through a pad of Celite on a glass frit filter into a three-necked, 2-L vessel. The flask is rinsed with 50 mL of dichloromethane and the rinse is filtered through the funnel. The 2-L vessel is then equipped with an overhead stirrer, thermometer, and water bath, and stirring is begun at 300–350 rpm. A solution of 30–40 mL of saturated aqueous sodium bicarbonate (0.4 mL/g of diacetonide) is added with stirring, followed by 130–140 g of sodium metaperiodate (2.0 mol equiv), added portionwise over 2–3 min. The resulting mixture is stirred while the internal temperature is maintained below 35°C with water bath cooling. After the solution is stirred for 2 hr, 35–50 g of magnesium sulfate (0.5 g/g of diacetonide) is added and stirring is continued for 20 min. The slurry is vacuum-filtered through a glass frit filter into a 2-L, one-necked, round-bottomed flask. The filter cake is removed, transferred back into the three-necked vessel, 200 mL of dichloromethane is added, and the resulting slurry is stirred for 10 min. The slurry is vacuum-filtered and the filtrate is added to the one-necked flask.
The filtrate-containing flask is equipped with a 12"-Vigreux column, distillation head, receiver, and heating mantle, and dichloromethane is removed by distillation (head temperature to 40°C). The residual oil is cooled and transferred to a 250-mL, round-bottomed flask and the flask is equipped with a simple distillation head, cow receiver, and heating mantle. After a brief forerun (2–3 g), product is collected by distillation at 30 mm (65–120°C)
into a chilled receiver (5°C) to afford 54–68 g (75–85%) of crude 2,3-O-isopropylidene-D-glyceraldehyde. The crude product is transferred to a 100-mL, round-bottomed flask equipped with a 6"-Vigreux column, cow receiver, and heating mantle, and redistilled at 30 mm, collecting the fraction distilling at 67–73°C into a chilled receiver to afford 50–64 g of product (70–80%, 34–45% overall).
Reference: Organic Syntheses, Coll. Vol. 9, p.450; Vol. 72, p.6
2.7.1 其他
1,2-二醇的氧化相关文献： 1,2-二醇可以通过甲磺酰化然后碱消除合成酮。

3
31.MsCl/Et 3N
Reference:Tetrahedron Letters ，1990, Pages 463-464
DMDO(dimethyldioxirane)a ，NaOCl/HAC b 可选择性氧化仲醇
OH
O
Reference: a ）Tetrahedron Letters 1994, 8477-8480
b ）Tetrahedron Letters 1982, 4647-4650
3．由卤化物合成醛酮
3.1 由伯卤甲基和仲卤甲基的氧化合成醛酮
伯卤甲基和仲卤甲基可以通过多种方法的氧化成醛酮。

通常所用的氧化剂有DMSO （Kornblum 反应）、硝基化合物（Hass 反应）、乌洛托品（Sommelet 反应）、对亚硝基二甲苯胺氧化吡啶翁盐（Krohnke 反应）、胺氧化物等。

3.1.1 用DMSO 氧化（Kornblum 反应）
将反应活性好的卤甲基化合物与DMSO 反应，生成烷氧基锍基，然后起β-消除反
应而得醛。

本法对于活性较高的卤甲基化合物收率很好，对于活性低的卤甲基化合物，可先将其变成碘化物，然后再进行反应可得较高收率。

（N. Kornblum., J. Am. Chem. Soc., 1959, 81, 4113.）
84%Br O O O
对于仲卤代物经常发生消除反应，酮的收率低下。

但对α-卤代酮或α-卤代酯等活性较高的仲卤代物而言，酮的收率也较高。

（N. Kornblum., J. Am. Chem. Soc., 1957, 79, 6562.） O Br O O DMSO
150 C
95%
3.1.1 .1 Kornblum 反应示例：
DMSO, 150 o C
I O
To a flask, protected from light, containing 11 g (0.0394 mol) of silver tosylate in 100 mL of acetonitrile at 0-5℃ is added 7.0 g (0.0309 mol) of 1-indoheptane. The product is allowed to come to room temperature overnight, added to ice water, and then extracted with ether. The dried ether solution is concentrated under reduced pressure to yield an aily residue which is added to a flask containing 150 mL of dimethyl sulfoxide and 20 g of sodium bicarbonate at 150℃. Nitrogen is bubbled through the mixture. After 3 min at 150℃ the reaction mixture is cooled rapidly to room temperature and the product, 6.9 g (70%), is isolated as the 2,4-dinitrophenylhydrazine, mp 106-107℃. For benzyl halides the same procedure is used except that tosylate is heated for 5 min at 100℃ in the DMSO-sodium bicarbonate mixture. For example, p-methylbenzyl bromide gives a 65% yield of p-tolualdehyde.
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。

ArCH 2X + (CH 3)2C=NO 2-Na + ArCH 2ON=C(CH 3
)2 ArCHO
25-80o C abs. EtOH Ar = C 6H 5, C 6H 4CH 3, C 6H 4COCH 3, C 6H 4COOCH 3, C 6H 4CF 3, C 6H 4CN, C 6H 4Br
X = Cl, Br, I 70-80%
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-Weyl7/1,194 (1954). Synthetic applications: S. Miyano et al.,Bull. Chem. Soc. Japan59, 3285 (1986); D. Evans et al.,Heterocycles26, 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。