Checked by J. Lazar and B. C. McKusick.
1. Procedure
A.
Nitronium tetrafluoroborate (Note 1).
Caution! Hydrogen fluoride is very hazardous. Caution is also called for in the use of boron trifluoride. All operations must be carried out in a hood, and the precautions outlined in (Note 2) should be followed. A
1-l. three-necked polyolefin flask (Note
3) is provided with a short inlet tube for
nitrogen, a
long inlet tube for gaseous
boron trifluoride, a
drying tube, and a
magnetic stirring bar (Note
4). The flask is immersed in an
ice-salt bath and flushed with dry
nitrogen. Under a gentle stream of
nitrogen and with stirring, the flask is charged with
400 ml. of methylene chloride,
41 ml. (65.5 g., 1.00 mole) of red fuming nitric acid (95%), and
22 ml. (22 g., 1.10 moles) of cold, liquid, anhydrous hydrogen fluoride (Note
5).
Gaseous
boron trifluoride (136 g., 2.00 moles) from a cylinder mounted on a scale is bubbled into the stirred, cooled reaction mixture (Note
6). The first mole is passed in rather quickly (in about 10 minutes). When approximately 1 mole has been absorbed, copious white fumes begin to appear at the exit, and the rate of flow is diminished so that it takes about 1 hour to pass in the second mole; even at this slow rate, there is considerable fuming at the exit. After all the
boron trifluoride has been introduced, the mixture is allowed to stand in the cooling bath under a slow stream of
nitrogen for 1.5 hours. The mixture is swirled, and the suspended product is separated from the supernatant liquid by means of a
medium-porosity, sintered-glass Buchner funnel (Note
7). The gooey solid remaining in the flask is transferred to the funnel with the aid of two
50-ml. portions of nitromethane. The solid on the funnel,
nitronium tetrafluoroborate, is washed successively with two
100-ml. portions of nitromethane and two
100-ml. portions of methylene chloride. In order to protect the salt from atmospheric moisture during the washing procedure, suction is always stopped while the salt is still moist. The moist salt is transferred to a
round-bottomed flask and dried by evaporating the solvent (Note
8). At the end of the procedure the flask can be gently heated to 40–50° (Note
9). The yield of colorless
nitronium tetrafluoroborate is
85–106 g. (
64–80%) (Note
10), (Note
11), (Note
12). It is stored in a wide-mouthed polyolefin bottle with a screw cap. The edge of the cap is sealed with paraffin wax after it is screwed on.
B.
3,5-Dinitro-o-tolunitrile. A
500-ml. four-necked flask is equipped with a
mechanical stirrer, a
dropping funnel, a
thermometer and an inlet for dry
nitrogen (Note
13). It is baked thoroughly by means of a Bunsen flame and allowed to cool to room temperature with a slow stream of dry
nitrogen passing through it. The flask is charge, preferably in a dry box, with
335 g. of tetramethylene sulfone (Note
14) and
73.1 g. (0.55 mole) of nitronium tetrafluoroborate. The thermometer is adjusted so that the bulb is immersed in the liquid. The reaction mixture is stirred well and kept at 10–20° by means of an
ice bath while
58.5 g. (0.50 mole) of freshly distilled o-tolunitrile3 is added dropwise. The
nitronium tetrafluoroborate only partially dissolves in the
tetramethylene sulfone (Note
15), but through good stirring a homogeneous suspension can be obtained. As the dissolved nitronium salt reacts with the nitrile, more and more salt dissolves until all of it is in solution. The addition of
o-tolunitrile requires 25–35 minutes.
After the addition is complete, the cooling bath is removed and stirring is continued for 15 minutes at 35°. The dropping funnel is removed,
74.5 g. (0.56 mole) of nitronium tetrafluoroborate is added, and the opening of the flask is closed with a
glass stopper. The well-stirred reaction mixture is heated by an electric heating mantle to 100° in 15 minutes and kept at 100–115° for 1 hour. The reaction mixture is allowed to cool to room temperature with continued stirring and is then poured into 800 g. of ice water. Crude
3,5-dinitro-o-tolunitrile separates on top of the aqueous mixture as a dark oil that solidifies after standing a few minutes. The solid is collected on a Buchner funnel. It is triturated on the funnel with five 50-ml. portions of cold water and with
40 ml. of ice-cold ethanol. After being dried in a
vacuum desiccator, the crude nitrile weighs
75–84 g., m.p.
60–65°. Recrystallization from about
110 ml. of hot methanol gives
50–55 g. (
48–53%) of
3,5-dinitro-o-tolunitrile, m.p.
82–84° (Note
16).
2. Notes
2.
Because of the hazardous nature of anhydrous hydrogen fluoride, adequate precautions should be taken to protect the head, eyes, and skin. Rubber gloves, an apron, and a plastic face mask are strongly recommended. All operations should be carried out in a hood. If
hydrogen fluoride comes in contact with the skin, the contacted area should be thoroughly washed with water and then immersed in ice water while the patient is taken to a physician. After completion of the reaction, all equipment should be washed with liberal quantities of water.
Note! Burns caused by hydrogen fluoride may not be noticed for several hours, by which time serious tissue damage may have occurred.
4. An egg-shaped stirrer seems to work best. As the reaction proceeds, the precipitating
nitronium tetrafluoroborate prevents the stirring bar from operating. This is not serious if the reaction mixture is shaken occasionally.
5. It is convenient to condense anhydrous
hydrogen fluoride, b.p.
19.5°, from a cylinder into a small calibrated polyolefin flask immersed in a mixture of dry ice and
acetone. As
hydrogen fluoride is very hygroscopic, it should be carefully protected from atmospheric moisture, preferably by maintaining an atmosphere of dry
nitrogen over it, otherwise by means of a drying tube. The
hydrogen fluoride is then simply poured into the reaction flask.
6. The temperature of the reaction is not critical, but the reaction is slower at higher temperatures because of the lower solubility of
boron trifluoride in the solvent.
7. Since free
hydrogen fluoride is no longer present, filtration can be carried out with glass or porcelain equipment. However, commercially available polyolefin Buchner funnels and filter flasks are preferred.
8. Kel-F grease is recommended for ground-glass joints.
Nitronium tetrafluoroborate slowly attacks silicone stopcock grease, causing air to enter the flask.
10.
Nitronium tetrafluoroborate is very hygroscopic. It is stable as long as it is anhydrous, but it is decomposed by moisture, and all transfers should be in a dry box. Its purity can be checked by conventional elemental analysis. However, because of the hygroscopic nature of the salt, the submitters have found it convenient to use neutron activation analysis (B, F, N, O) of samples sealed into polyolefin sample holders. Lange's method
4 for the determination of
BF4− as the nitron salt gives good results but requires considerable care to achieve reproducibility.
12.
Nitronium tetrafluoroborate slowly attacks
polyethylene and
polypropylene, but apparatus made of these materials will last for several preparations of the salt.
13. The entire operation should be carried out in an atmosphere of dry
nitrogen. If dry
nitrogen is not available, rigorously anhydrous conditions should be maintained with the help of a drying tube.
14.
Tetramethylene sulfone is commercially available from the Shell Chemical Company and the Phillips Petroleum Company.
16. This is pure enough for most purposes. An analytical sample melted at
86.5–88.4°.
3. Discussion
4. Merits of the Preparation
Nitration of aromatic rings by
nitronium tetrafluoroborate is a general method. Fifty-seven arenes, haloarenes, nitroarenes, arenecarboxylic esters, arenecarbonyl halides, and arenecarbonitriles have been nitrated in high yield by this reagent.
8 The method is particularly convenient for nitrating aromatic compounds susceptible to acid-catalyzed hydrolysis. For example, although mononitration of arenecarbonitriles is easily accomplished by conventional nitrating agents, dinitration is not. The reason is that the forcing conditions required for dinitration (strongly acid media and higher temperatures) bring about hydrolysis (and oxidation) of the nitrile group. In contrast, nitrations with
nitronium tetrafluoroborate can be carried out in nonaqueous acid-free systems, where the only acid originates from proton elimination during nitration. In the basic solvent used, this acid concentration generally is not sufficient to cause any detectable hydrolysis (or oxidation).
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