【硝化反应】卤代烃的硝化反应

从卤代烷制备硝基烷烃已被广泛用于有机合成。许多在天然产物合成中使用的硝基化合物都是通过硝化卤代烃得来的。

卤代烃与金属亚硝酸盐反应是制备硝基烷烃的最重要方法之一。而各种金属亚硝酸盐中，亚硝酸银（Victor-Meyer反应），亚硝酸钾或亚硝酸钠（Kornblum反应）是其中比较常用的，下表中列举了一些典型的反应例子¹。

一级硝基烷烃和α,ω-二硝基烷烃很容易的有它们的卤代烃衍生物与亚硝酸银在水中反应得到。溴代烷和碘代烷使用该方法都可以得到很好的收率，而且该方法对其他活性官能团影响很小。如下面例子所示²

To a water solution (2 mL) of the iodoalkane (1 mmol) was added AgNO₂ (4 mmol) and the reaction flask was wrapped with silverpaper to protect the reaction mixture from light. After being stirred at 60 ^oC, the reaction mixture was filtered, extracted with EtOAc, and dried over Na₂SO₄ and the solved was evaporated under reduced pressure. The crude products were purified by column chromatography (hexane:EtOAc, 95:5) to give the nitrocompound with 65% yield.²

α-硝基丁酸乙酯是由α-溴代丁酸乙酯与亚硝酸银在DMF中制备得到，收率是68-75%³。亚硝酸银的溶解度在DMSO 比DMF中好很多，浓度大，因此在DMSO中的反应比在DMF中反应时间短。

Ethyl α-bromobutyrate (58.5 g., 0.30 mol) is poured into a stirred mixture of 600 mL of DMF, 36 g of sodium nitrite (0.52 mol), and 40 g of anhydrous phloroglucinol (0.32 mol). Stirring is continued for 2.5 hours at room temperature, then the reaction mixture is poured into 1.2 L of ice water layered over with 300 mL of ether. After separation of the upper layer, the aqueous phase is extracted with four 100 mL. portions of ether. The combined extracts are washed with four 100 mL portions of water and then dried over anhydrous magnesium sulfate. The ether is distilled through a small column under reduced pressure. The residual yellow liquid is transferred, with the aid of a little anhydrous ether, to a 100-ml flask, and the remaining solvent is distilled through the column under reduced pressure. Rectification of the residue yields 2–3 g. of forerun boiling in the range 33-71°/1 mm which is followed by 33-36 g (68–75%) of colorless ethyl α-nitrobutyrate. 

因此，脂肪卤化物和α-卤代酯类化合物与亚硝酸钠的反应提供了制备脂肪族硝基化合物和α-硝基酯化合物的方法。但是，溴代乙酸乙酯是个例外，该方法不能将其转化成相应的硝基乙酸乙酯化合物。⁴这是因为硝基乙酸乙酯的酸性氢可以继续跟亚硝酸钠反应生成氧化的副产物。同样，卞溴与亚硝酸钠在25°C 反应时只能得到副产物苯甲酸。而在低温反应(-16°C)时才能得到苯基硝基甲烷⁴。

最近文献报道了一些硝化脂肪卤代物的优化方法。例如, KNO₂反应中加入18-crown-6⁵，或亚硝酸阴离子负载树脂(amberlite IRA 900)都能够有效的提高硝化反应的收率⁶。

【参考文献】

2. RobertoBallini,* Luciano Barboni, and Guido Giarlo J. Org. Chem., 69, 6907-6908 (2004)

连接全球科学家与优质供应商，创建经济有效的科研用品交易平台

览博网