活潑 C-H 化合物的硝化反應
活潑亞甲基化合物在親電硝化劑如烷基硝酸酯作用下發生硝化反應，通常都會經歷碳負離子中間體的反應過程。烷基硝酸酯硝化反應方法已被廣泛用於芳香硝基甲烷的製備。帶有吸電子基團的甲苯衍生物，在氨基鉀存在下在液氨中，與烷基硝酸酯發生硝化反應，如下面例子所示1。
Into an oven-dried 500-ml round-bottom four-necked flask equipped with Dry Ice condenser, thermometer, mechanical stirrer, and addition funnel were placed, at -33oC, 250 ml of liquid ammonia, acrystal of ferric nitrate nonahydrate, and 2.95 g (0.075 g atom) of potassium. After potassium amide had formed, a solution of 5.9 g (0.05 mol) ofp-tolunitrile in 15 ml of ether was added dropwise within 2 min. The mixture was stirred 15 min at -33oC and then 10.51 g (0.1 mol) of propyl nitrate was added in 5 min [CAC"TION! The first drops of alkyl nitrate should be added slowly because a considerable exotherm might develop], while the temperature was kept at -33oC with a Dry Ice-CHC13-CC14bath. The mixture was stirred for an additional 30 min at -33oC, and the ammonia was allowed to evaporate while replacing it with anhydrous ether. Filtering and drying the solid at 25oC (0.7 mm) gave 17.8 g of crude potassiump- cyanophenylmethanenitronate.To a suspension of the crude salt in 150 ml of anhydrous ether at -40oC was added 15 g (0.25 mol) of glacial acetic acid. The mixture was stirred overnight in anice-salt bath, filtered and concentrated in uacuo to afford 3.78 g (46.6%) ofp- cyano-a-nitrotoluene, mp 94-96oC.1
在鹼性條件下使用烷基硝酸酯對離域碳負離子進行硝化反應是製備硝基化合物的有效方法。芳香族的硝基甲烷可以用這種方法方便的製備得到2。對於富電芳香類硝基甲烷化合物的製備，這是個很好的方法，這類化合物通常較難通過對應的鹵代烴硝化得到。
A solution of the methoxyphenylacetic acid (10.2 mmol) in THF (8 mL) was added to a magnetically stirred, chilled (0oC) solution of LDA (23.5 mmol of n-butyllithium and 24.5 mmol of diisopropylamine) and HMPA (10.2 mmol) in THF(20 mL) under nitrogen. The yellow solution was stirred at room temperature for 1.5 h and then chilled to -60oC. Addition of methyl nitrate (1.9 mL, 30.6 mmol) to the dianion solution produced a brownish yellow solution, which faded to the original yellow color. The reaction was stirred for 1 h, and then acetic acid(1.4 mL) was added. The mixture was allowed to warm to 0oC, at which point hydrochloric acid (12 mL, 4N) was added and evolution of carbon dioxide occurred. Water (20 mL) and ether (20 mL) were added and the layers separated. The water layer was extracted again with ether (20 mL), and the combined organic phases were successively washed with water (20 mL), aqueous bicarbonate(2×25 mL), hydrochloric acid (2×20 mL of 0.01 N), water (2×20 mL), and brine. The organic solution was dried (MgSO4), filtrered, and evaporated at reduced pressure. The crude product was purified by silica gel chromatography to give the nitro compound with 66% yield.2
環丙烷羧酸酯在鹼性條件下轉化為相應的烯醇衍生物，該烯醇化物可以被硝酸異戊酯硝化，得到1-硝基環丙烷-1-羧酸酯，它是含環丙烷的α-氨基酸的前體。3
To a solution of DBHA-ester1(4.56 g, 15 mmol) in 30 mL of THF stirred at -75oCwas added dropwise under argon tBuLi (15 mmol). After 30 min a THF solution of isopentyl nitrate (2.20g, 16.5 mmol) was added. The mixture was allowed to warm up to room temperature within 2 h and poured onto 20 mL of sat. aq. NH4Cl. After separation of the twolayers, the water phase was twice extracted with 20 mL of ether. The organicphases were combined, washed twice with sat. aq. NaCl, dried over Na2SO4and concentrated. The residue was purified by flash chromatography (pentane:acetone= 95:5) to give 3.7 g (71%) of compound2as a colorless solid.3
【參考文獻】
1. Feuer, H., and H. Friedman.J. Org. Chem., 40, 187 (1975).
2. Hauser, F. M., and V. M. Baghdanov.J. Org. Chem., 53, 2872 (1988).
3. Haner, R., and D. Seebach.Chimia, 39, 356 (1985).
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