用TosMIC 直接從酮轉(zhuǎn)化為氰基
對甲苯磺酰甲基異氰(TosMIC) 是有機(jī)化學(xué)官能團(tuán)轉(zhuǎn)換反應(yīng)中最有用的多功能試劑和合成子之一。TosMIC 在雜環(huán)合成中可以用來方便地制備咪唑、噻唑、 惡唑、三氮唑、吲哚、吡咯等。TosMIC 參與的增加一個碳原子的還原氰基化反應(yīng)和二烷基化反應(yīng)具有獨到之處。
TosMIC與酮生成腈的還原氰基化反應(yīng)是該試劑最特征的反應(yīng)之一。反應(yīng)的機(jī)理是TosMIC在堿的存在下生成碳負(fù)離子與酮羰基發(fā)生親核加成反應(yīng)，然后失去磺?；图柞；呻鎇2]。該反應(yīng)需要使用過量的堿，常用的堿為t-BuOK。反應(yīng)一般在室溫下數(shù)小時內(nèi)完成，產(chǎn)率中等到較高水平 (式1，式2)[3,4]。TosMIC與甾體17-酮反應(yīng)時，生成兩種異構(gòu)體的混合產(chǎn)物 (式3)[5]。
TosMIC 與鹵代烴發(fā)生烷基化反應(yīng)，生成多一節(jié)碳的酮[6,7]。分子間的烷基化反應(yīng)生成對稱或者不對稱的鏈狀酮，分子內(nèi)的烷基化反應(yīng)生成相應(yīng)的環(huán)狀酮 (式4，式5)[6,7]。
TosMIC 與α,β-不飽和羰基化合物反應(yīng)生成吡咯環(huán)的反應(yīng)一般給出較好的產(chǎn)率，羰基或者其它拉電子基團(tuán)的存在對反應(yīng)活性的影響非常大 (式6，式7)[8,9]。最近有人報道簡單的芳基乙烯就可以與TosMIC 發(fā)生形成吡咯環(huán)的反應(yīng) (式8)[10]。
酮轉(zhuǎn)化為氰基示例
To a 250 mL round-bottomed flask equipped with condenser and nitrogen inlet were added 4.34 g (23.49 mmol) N-carboethoxyperhydroazepin-4-one (prepared according to the procedure given by Z. G. Finney and T. N. Riley, J. Med. Chem., 23, 895, 1980), 10.53 g(54.02 mmol) tosylmethylisocyanide and 117 mL 1,2-dimethoxyethane. The solution was cooled to 0 deg C and 2.48 mL (54.02 mmol) ethanol and 9.21 g (82.2 mmol) potassium t-butoxide were added. The mixture was heated at 60 deg C for 18 hours, cooled and concentrated. The residue was taken up in ethyl acetate, washed with brine, dried over sodium sulfate and concentrated to give an oil. The oil was purified by chromatography on silica gel using hexane/ethyl acetate as eluent to afford 4.6 g (100percent) of oil.
用2,4,6- 三異丙基磺酰肼-KCN 將酮轉(zhuǎn)化為氰基
3-Quinuclidinone (24.2 g, 0.19 mol) and 2,4,6-triisopropylbenzenesulphonohydrazide (72g, 0.24 mol) were stirred together in anhydrous MeOH (250 mL) for 3 h. Potassium cyanide (33.8 g, 0.51 mol) was added and the mixture was heated under reflux for 5 h. The residue after evaporation of the solvent was partitioned between water and CH2C12. The organic phase was dried and evaporated and the residue was fractionally distilled under reduced pressure to give 3-cyanoquinuclidine (32, 6.1 g).
