Checked by P. B. Sargeant and B. C. McKusick.
1. Procedure
A
1-l. polyethylene bottle is fitted with a
three-holed rubber stopper. Three lengths of 0.25-in. (6-mm.) stiff polyethylene tubing extend through the stopper into the bottle. One length of tubing serves as an inlet tube for dry
nitrogen, which is monitored by first bubbling through mineral oil. The second tube, the
gas-outlet tube, carries a
polyethylene drying tube packed with indicating Drierite®. These tubes extend only about 2 cm. into the bottle. The third tube serves as an inlet for anhydrous
hydrogen fluoride and extends halfway into the bottle; it is connected to a
hydrogen fluoride cylinder by a short length of Tygon
® tubing secured to the cylinder outlet by
copper wire. The bottle contains a
Teflon®-covered magnetic stirring bar.
The bottle is flushed with dry
nitrogen, and a slow stream of
nitrogen passes through the bottle during all subsequent operations to ensure the exclusion of atmospheric moisture (Note
2).
N-Bromoacetamide (80 g., 0.58 mole) is added (Note
3). The bottle is cooled in a mixture of dry ice and
acetone, and
250 ml. of anhydrous ether is added with efficient magnetic stirring. About
100 g. (100 ml., 5 moles) of anhydrous hydrogen fluoride is allowed to condense into the bottle with magnetic stirring (Note
4). This requires about 2 hours.
1-Heptene (49 g., 0.50 mole) (Note
3) is mixed with
50 ml. of anhydrous ether. The solution is added during 20 minutes through what was originally the
nitrogen inlet; the
hydrogen fluoride inlet now serves as the nitrogen inlet. The reaction mixture is stirred in the dry
ice bath for an additional 4 hours. The dry ice bath is replaced by an ice bath, and the mixture is stirred for 40 minutes. It is then allowed to stand overnight in a mixture of dry ice and
acetone in a
Dewar flask.
A solution of
690 g. (5.0 moles) of potassium carbonate in 2 l. of distilled water is prepared in a
4-l. polyethylene beaker or pail, and 500 g. of crushed ice and
300 ml. of ether are added. The cold reaction mixture is cautiously added to the carbonate solution with stirring. The pH of the aqueous layer becomes about 9. The
ether layer is separated, and the aqueous layer is extracted with three
200-ml. portions of ether. The
ether solutions are combined and washed with three 100-ml. portions of water. The
ether solution is dried over anhydrous
sodium sulfate, and the
ether is removed by distillation. The oily residue is fractionated through a
15-cm. Vigreux column under reduced pressure. There is a fore-run of about 0.5 ml., and then
59–75 g. (
60–77%) of
1-bromo-2-fluoroheptane is collected at
70–78° (15 mm.);
n25D 1.4408–1.4420. According to vapor phase chromatography, it is about 90% pure (Note
5).
2. Notes
1. Because of the hazardous nature of anhydrous
hydrogen fluoride,
adequate precautions should be taken to protect the head, eyes, and skin. Use of rubber gloves, an apron, and a plastic face mask is strongly recommended. All operations should be carried out in a hood. After completion of the reaction, all equipment should be washed with liberal quantities of water. A bottle containing
magnesium oxide paste in glycerin should be available in case of emergency.
Note! Burns caused by hydrogen fluoride may not be noticed for several hours, by which time serious tissue damage may have occurred.
The checkers recommend that, if
hydrogen fluoride comes in contact with the skin, the contacted area be thoroughly washed with water and then immersed in ice water while the patient is taken to a physician.
2. Moisture or inefficient stirring reduces the yield considerably.
4. The amount of
hydrogen fluoride is not critical. The amount of
hydrogen fluoride may be estimated by condensing in enough to increase the volume of the reaction mixture by 100 ml.
5. According to vapor phase chromatography in a 6-ft. column at 150° over silicone grease, the product contains about 8% of one impurity and 2% of another. It is sufficiently pure for conversion to
2-fluoroheptanoic acid.
2
3. Discussion
4. Merits of the Preparation
The method is general for forming
vic-bromofluorides, which in turn are useful intermediates; this is exemplified in their conversion to 2-fluoroalkanoic acids.
2 The procedure can be applied, with minor modification, to many types of alkenes.
3
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