【硝化反应】活泼 C- H 化合物的硝化反应
活泼亚甲基化合物在亲电硝化剂如烷基硝酸酯作用下发生硝化反应，通常都会经历碳负离子中间体的反应过程。烷基硝酸酯硝化反应方法已被广泛用于芳香硝基甲烷的制备。带有吸电子基团的甲苯衍生物，在氨基钾存在下在液氨中，与烷基硝酸酯发生硝化反应，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 -33 oC, 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) of p-tolunitrile in 15 ml of ether was added dropwise within 2 min. The mixture was stirred 15 min at -33 oC 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 -33 oC with a Dry Ice-CHC13-CC14 bath. The mixture was stirred for an additional 30 min at -33 oC, and the ammonia was allowed to evaporate while replacing it with anhydrous ether. Filtering and drying the solid at 25 oC (0.7 mm) gave 17.8 g of crude potassium p- cyanophenylmethanenitronate.To a suspension of the crude salt in 150 ml of anhydrous ether at -40 oC 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 94-96 oC.1
在碱性条件下使用烷基硝酸酯对离域碳负离子进行硝化反应是制备硝基化合物的有效方法。芳香族的硝基甲烷可以用这种方法方便的制备得到2。对于富电芳香类硝基甲烷化合物的制备，这是个很好的方法，这类化合物通常较难通过对应的卤代烃硝化得到。
A solution of the methoxyphenylacetic acid (10.2 mmol) in THF (8 mL) was added to a magnetically stirred, chilled (0 oC) 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 -60 oC. 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 0 oC, 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
环丙烷羧酸酯在碱性条件下转化为相应的烯醇衍生物，该烯醇化物可以被硝酸异戊酯硝化，得到1-硝基环丙烷-1-羧酸酯，它是含环丙烷的α-氨基酸的前体。3
To a solution of DBHA-ester 1(4.56 g, 15 mmol) in 30 mL of THF stirred at -75 oC was 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 Na2SO4 and concentrated. The residue was purified by flash chromatography (pentane:acetone= 95:5) to give 3.7 g (71%) of compound 2 as a colorless solid.3
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