硝基化合物，特別是芳香族硝基化合物，是具有悠久歷史的一類(lèi)化合物。硝基化合物是合成染料，香料，藥物，和炸藥的重要中間體，廣泛應(yīng)用于化學(xué)工業(yè)，制藥和有機(jī)合成的各個(gè)領(lǐng)域中。因此，硝基化合物的制備是研究地最多，應(yīng)用也最為廣泛的一類(lèi)有機(jī)反應(yīng)。
同時(shí)，由于硝化，特別是芳香類(lèi)化合物的硝化，需要過(guò)量的硝酸及硫酸等強(qiáng) 酸，產(chǎn)生大量的廢氣和廢酸，使之成為污染環(huán)境的一大因素。
硝基化合物的制備有多種途徑，烴類(lèi)的直接硝化，鹵素取代及胺，肟的氧等，如下圖所示：
其中芳烴或脂肪烴的直接硝化是制備硝基化合物最簡(jiǎn)捷的途徑。常見(jiàn)的硝化試劑歸納如下：
? 硝酸 Nitric acid
Alone or in combination with H2SO4 , H3PO4 , HClO4 , HF(BF3 ), (CH3CO)2O, (CF3 CO) 2 O,CF3CO2H, MeSO3H, CF3SO3H, FSO3 H(SbF5 ), Nafion-H, sulfonated resins, clays, molecular sieves, graphite
? 硝酸鹽 Nitrate salts
AgNO3 /BF3 , KNO3 /H2SO4 , K(Na)NO3 /TMSCl/AlCl3 , Cu(NO3 )2 /(CH3CO)2O,NH4NO3 /(CF3CO)2O, (NH4 )2Ce(NO3)
? 硝酸酯 Nitrate esters
BuONO2/Nafion-H,MeONO2/BF3, Me3SiONO2,acetone cyanohydrin nitrate
? 硝?；衔?Nitryl compounds
NO2BF4 , NO2PF6 , NO2ClO4 , NO2Cl(F), MeCO2NO2 , CF3CO2NO2 , PhCO2NO2 ,N-nitropyridinium nitrate
? 氧化氮 Nitrogen oxides
NO2－O3 , N2O3/BF3, N2O4/H2SO4 ,N2O4/AlCl3 , nBuLi/N2O4 ,N2O5 , N2O5/HNO3 ，N2O5/SO2
? 硝烷 Nitroalkanes
C(NO2)4 , CH(NO2)3 , (O2N)3CC(NO2)
在有機(jī)合成中，通過(guò)硝基化合物可以實(shí)現(xiàn)多種轉(zhuǎn)換，如下圖所示：
1、芳香族硝基化合物的合成
芳烴的直接硝化是合成芳香族硝基化合物最重要的方法?？墒狗紵N硝化的試劑很多，最常用的硝酸及其鹽、以及硝酸酯、硝酸鎓鹽、氧化氮類(lèi)等。通常，硝化試劑的選擇取決于硝化試劑及芳香族化合物的反應(yīng)活性、硝化的區(qū)域選擇性和一元硝化及多硝化的控制等因素。另外，重氮鹽、硼酸被硝基取代，苯胺氧化，也能合成芳香族硝基化合物。
HNO3作為硝化試劑反應(yīng)示例：
硝酸是最常用的硝化試劑之一，它能使許多芳香族化合物發(fā)生硝化，普通硝酸和發(fā)煙硝酸都能用于硝化。
A wide-mouth 1-L flask is supported inside a water bath. The flask is fitted with a moderate-speed stainless-steel propeller-type stirrer, and nitric acid (sp. gr. 1.4, 350 mL.) at 20° is poured into it. Veratraldehyde (70 g, 0.42 mole) is crushed at least as fine as rice grains and is slowly added in small portions to the acid. The rate of addition should be such that it requires about 1 hour to add all the aldehyde.
The internal temperature is checked from time to time and should be held between 18° and 22°. The mixture is stirred for 10 minutes after the addition of the last of the aldehyde. The mixture is then poured into 4 L of vigorously agitated cold water. From this point onward the protection of the product from light is extremely important. The stirring is continued for a few minutes; then the batch is filtered through Büchner funnel. The filter cake is recrystallized from 95% ethanol to give 55–60 g of pure material, melting at 132–133°.
2、HNO3 /H2SO4 作為硝化試劑反應(yīng)示例
硝酸與硫酸組成的混酸是比硝酸更強(qiáng)的硝化劑，根據(jù)底物活性的高低可以使用普通的硝酸或發(fā)煙硝酸，這個(gè)方法可以順利地得到多硝基取代的產(chǎn)物。
A 5-L three-necked flask fitted with an all-glass addition funnel and two condensers is charged with 770 mL of concentrated sulfuric acid and 1.3 L of 90% fuming nitric acid. The solution is heated under gentle reflux, and a solution of (73 g, 0.4 mol) of 9-fluorenone in 840 mL of concentrated sulfuric acid is added from the dropping funnel over a 1-hour period. After the fluorenone addition is complete, a solution of 950 mL of fuming nitric acid in 1120mL of concentrated sulfuric acid is added dropwise during 8.5 hours to the gently refluxing
reaction mixture. The heating jacket is turned off and the solution is allowed to stand for 10 hours. The reaction mixture is poured into 5 gallons of water in two 5-gal Crocks. The light yellow precipitate is washed with water, twice by decantation, filtered, washed several times with water and sucked dry, and finally is dried in a vacuum oven at 80° for 10 hours. The yield of crude 2,4,5,7-tetranitrofluorenone, mp 249–253°, is 105–117 g (72–80%). This solid is recrystallized from 1.6 L of acetic acid containing 100 mL of acetic anhydride. The hot solution is filtered through a fluted filter and cooled rapidly to yield 80–86 g (51–54%) of 2,4,5,7-tetranitrofluorenone, mp 253.0–254.5°
3、硝酸鹽 /H 2 SO 4 作為硝化試劑反應(yīng)示例
硝酸鹽 /H 2 SO 4 是硝化常用的試劑，通常使用的硝酸鹽是硝酸鉀，反應(yīng)條件溫和，操作方便，反應(yīng)迅速，通常在 0 o C進(jìn)行，缺點(diǎn)是選擇性不好。
4-bromo-2-tert-butylphenyl methyl carbonate (470 g, 1.67 mol) is dissolved in conc. H2SO 4 (1000 mL) at 0 ℃ . KNO 3 (253 g, 2.5 mol) was added in portions over 90 minutes to the above solution and the reaction mixture is sequentially stirred for 2 hours at 0 ℃ . The mixture is poured into 20 L ice-water. The resulting precipitate is collected and washed with water thoroughly, dried and recrystallized from ether to give the pure product (332 g, yield 60%)。
4、HNO3 /Ac2O 作為硝化試劑反應(yīng)示例
硝酸和醋酐混和，生成醋酸和硝酸的混酐（CH 3 COONO 2 ），是一個(gè)良好的硝化試劑，反應(yīng)條件比較溫和。
A 1 L three-necked round-bottomed flask, fitted with a dropping funnel and a mechanical stirrer, is cooled in an ice-salt mixture. To the flask are added freshly distilled cinnamaldehyde (55.5 g, 50 mL, 0.42 mole) and acetic anhydride (225 mL). When the temperature of the solution has reached 0–5°C, a solution of concentrated nitric acid (sp. gr. 1.42, 18 mL) in glacial acetic acid (50 mL) is added slowly through the dropping funnel while the mixture is stirred. The time of addition is 3–4 hours, during which the temperature is kept below 5°. After the addition is complete, the mixture is allowed to warm slowly to room temperature. The reaction flask is then dismantled and stoppered, and the reaction mixture is allowed to stand 2 days.
At the end of this time, hydrochloric acid (20%) is added cautiously to the cooled solution until a precipitate begins to appear. The addition of acid is then stopped, and the solution is allowed to cool in an ice bath or refrigerator until precipitation of the solid is completed. The light-yellow needles are collected on a Büchner funnel and dried in air. About 24 g of o-nitrocinnamaldehyde, mp 125–127°, is obtained. Additional product can be isolated by cautiously adding water to the mother liquor until precipitation is observed and then cooling the resultant mixture for several hours in an ice bath. Recrystallization from 95% ethanol gives 5–10 g. of o-nitrocinnamaldehyde, mp 126–127°. The total yield is 27–34g(36–46%).
5、硝酸或硝酸銨/ 三氟乙酸酐作為硝化試劑反應(yīng)示例
硝酸和三氟乙酸酐也是一個(gè)類(lèi)似的硝化試劑，硝酸也可用硝酸銨代替。
A mixture of trifluoroacetic anhydride (10 mL) and fuming nitric acid (2.4 mL) was chilled at –15oC and after 1 h a solution of furan-2-carbaldehyde (0.96 g, 10 mmol) in trifluoroacetic anhydride (2 mL) was slowly added to the reaction mixture keeping the temperature at -15oC. The reaction mixture was stirred at -15oC for 2 h and then the solvents were removed and pyridine (2 mL) was added to the reaction mixture, stirred for 15 min. And then the solvent was again removed and the oily residue was poured in ice and extracted with diethyl ether. The crude product was then purified over a silica gel column to give the pure product (0.96 g, 68 %).
5-Methylisoxazole (8.31 g, 0.1 mol) was dissolved in trifluoroacatic anhydride (74 g, 0.35mol= 50 mL, d = -1.487 g/mL), and ammonium nitrate (8.00 g, 0.100mol) was added in 0.5-gportions, keeping the reaction temperature between 25 and 30 "C. After complete addition, 'HNMR of a neat aliquot showed the mixture to contain 65% product and 35% starting isoxazole. Thus, another portion of ammonium nitrate (3.60 g, 0.045 mol) was added as above.After complete addition, 'H NMR analysis indicated that less than 5% of starting material remained. The mixture was poured onto ice water and extracted with chloroform (4 X 50 mL).The extracts were washed with water (250 mL), and this aqueous wash was extracted with chloroform (3 X 25 mL). The combined chloroform extracts were dried over magnesium sulfate and filtered, and the filtrate was concentrated giving a yellow oil [12.34 g (96%)], which was virtually pure as determined by 'H NMR. The oil was distilled to give the product (8.04 g, 63%) as a pale yellow liquid: bp 88-90 "C (18 Torr)
