发布时间 : 星期三 文章醛酮的合成-060331更新完毕开始阅读
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
a vacuum oven at 50°C, yielding 25.6–28.0 g. (62.9–68.8%) of 4-formylbenzenesulfonamide, m.p. 117–118°C.
Reference: Organic Syntheses, Coll. Vol. 6, p.631; Vol. 51, p.20
5.6.4有机金属试剂对腈加成合成酮示例
CN1. MeMgI2. H+O
To a flask containing 0.11 mol of methyl magnesium iodide (prepared from 7 mL of methyl iodide in 30 mL of ether containing 2.7 g of magnesium) is added 25 mL of benzene followed by 15 g (0.074 mol) of 9-cyanophenanthrene. The reaction mixture is refluxed for 3 h, cooled, and hydrolyzed with cold ammonium chloride solution. The benzene-ether layer is separated, shaken with cold dilute hydrochloric acid, and then refluxed for 1 h in order to hydrolyze the ketimine hydrochloride to the ketone. The ketone, which precipitates as an oil, is seperated, distilled under pressure, and then recrystallized from ethanol to yield 9.5 g (58%), mp 73-74℃.
Reference: E. Bachman, J. Am Chem. Soc., 1936, 58, 2098
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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
6. 由烯烃、芳环合成醛酮
烯烃及芳环的C=C双键经臭氧、氧化锇等作用而氧化断裂生成醛，是醛的重要合成法之一。此外，将烯烃变为醛的方法尚有用在Rh及Co催化下与氢及一氧化碳起反应的加氢甲酰化，硼氢化反应以及将芳环上的C-H直接转化为Li而起甲酰化反应等。
烯烃经加成-氧化、加成-还原、加成-水解、加成异构化以及一氧化碳插入反应等则能合成酮。
6.1 由烯烃臭氧氧化合成醛
烯烃及芳香环等与臭氧反应，先生成过氧化物，由于有爆炸危险不予分离，直接将其还原为醛。还原可用催化氢化、锌、碘化钠、磷化氢类化合物、亚磷酸、甲硫醚等方法。要是不予还原则经氧化分解得酸。
(CH3O)3PO3-50~ -70oCOOOCH3CO3HCHOCHO85%COOHCOOH90%
有多个双键共存时，臭氧化的选择性一般在电子密度高而位阻小的双键。芳香环的反应较迟钝，有不饱和侧链存在时优先选择氧化侧链双键。含杂原子的芳环对臭氧的稳定性大于苯环。
6.1.1由烯烃臭氧氧化合成醛示例： 5-formylvaleraldehyde
O3OO
To a stirred -78 oC solution of cyclohexene (15 mL) in 100 mL of dichloromethane was bubbled in ozone until light blue color appeared. Excessive ozone was removed by a nitrogen flow, then 60 mL of dimethyl sulfide was added. The mixture was left overnight, dried over sodium sulfate. The solvent and DMS were removed under low vacuum to afford 5-formylvaleraldehyde. The crude product could be used in other reactions without further purification.
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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
Reference:WO2004/94371
6.2 烯烃用OsO4/NaIO4氧化合成醛
与臭氧化法相比，OsO4/NaIO4是一种温和的烯烃氧化开裂法，在天然产物合成中很有用。烯烃先与OsO4反应生成锇酸酯，再用过碘酸钠氧化，发生开裂，在生成羰基化合物的同时，OsO4再生，所以OsO4用催化量即可。当生成的醛易于分子内缩合时，反应最好在两相系统中进行。
6.2.1 烯烃用OsO4/NaIO4氧化合成醛反应示例：
OAcOOAcONHNHOOAcCHOOAcO1ONHOAcCHOOAc3OsO4, NaIO42NHO
To a solution of 1 (1.8 mg) in THF (1 mL) was added OsO4 (excess) and then a solution of NaIO4, (excess) in H2O (1 mL). After a period of 1 hr, H2O (5 mL) was added and the aq. solution was extracted with three 5ml portions of CHCl3. The combined CHCl3 layers were dried over Na2SO4, and concentrated to give a residue, which was separated by preparation TLC (SiO2, 5% MeOH-CHCl3). Compounds 2 and 3 were obtained. Reference: Tetrahedron; 41; 6; 1985; 1007-1018.
6.3 烯烃经由有机硼化合物中间体的烯烃甲酰化合成醛
烯烃与甲硼烷反应所得的有机硼化合物能用各种方法转变为醛。用铬酸氧化时，所得醛的碳原子数不变。如与一氧化碳反应再进行氧化便得多一个碳原子的醛。要是与重氮乙醛反应，即可得增长二个碳原子的醛。通过与丙烯醛的加成，碳原子数可增加三个。
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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
PCC1. CO, MH2. H2O2RCH2CHORCH2CH2CHORCH2CH2CH2CHORCH2CH2CH2CH2CHO
RCH=CH2BH3(RCH2CH2)3BN2CHCHOCH2=CHCHO
6.5 由烯烃的甲酰化合成醛 6.5.1 Vilsmeyer 反应
此方法广泛应用于活性芳环，杂环，不饱和脂肪上（富电子）引入甲醛，-OH,-OR,-NR1R2,CH(OR)不影响反应，可用二氯甲烷，二氯乙烷或二氯苯作溶剂，也可不用反应溶剂。（A. Vilsmeier and A. Haack, Ber. 1937 119)
6.5.1.1 Vilsmeyer 反应示例一
POCl3,DMFNHCHO
In a 1-l. round-bottomed, three-necked flask fitted with an efficient mechanical stirrer, a drying tube containing drierite and a 125 mL dropping funnel is placed 288 mL (274g, 3.74 moles) of freshly distilled dimethylformamide. The flask and its contents are cooled in an ice-salt bath for about 0.5 hour, and 86 mL (144g, 0.94 moles) of freshly distilled phosphorous oxychloride is subsequently added with stirring to the dimethylformamide over a period of 0.5 hour. The pinkish color of the formylation complex may be observed during this step. The 125-mL dropping funnel is replaced with a 200 mL dropping funnel, and a solution of 100g (0.85 mole) of indole in 100 mL of dimethylformamide is added to the yellow solution over a period of 1 hour during which time the temperature should not rise above 10 ℃. Once the solution is well mixed, the dropping funnel is replaced with a thermometer, and the temperature of the viscous solution is brought to 35 ℃. The syrup is stirred efficiently at this temperature for 1 hour, or for 15 minutes longer than is necessary for the clear yellow solution to become opaque, canary-yellow paste. At the end of the reaction
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NH