Org. Synth. 1966, 46, 37
DOI: 10.15227/orgsyn.046.0037
[Heptanoic acid, 2-fluoro-]
Submitted by F. H. Dean, J. H. Amin, and F. L. M. Pattison1.
Checked by Michelle Moran and B. C. McKusick.
1. Procedure
A. 2-Fluoroheptyl acetate. A 1-l. two-necked flask is fitted with a thermometer reaching close to the bottom and a reflux condenser that has a calcium chloride tube in its end. It is charged with 29.6 g. (0.150 mole) of 1-bromo-2-fluoroheptane,2 22.5 g. (0.150 mole) of dry sodium iodide, 24.6 g. (0.30 mole) of anhydrous sodium acetate, and 600 ml. of dimethylformamide previously dried over anhydrous calcium sulfate. The mixture is stirred by a magnetic bar for 40 hours while being maintained at 120–130° by means of an electric heating mantle. The mixture is cooled to room temperature, diluted with 750 ml. of water, and extracted with 900 ml. of ether. The aqueous layer is extracted with two 150-ml. portions of ether, and the combined ether extracts are washed with five 150-ml. portions of water (Note 1). The ethereal solution is dried over anhydrous sodium sulfate. The ether is removed by distillation, and the residue is transferred to a Claisen flask with a 15-cm. indented neck. Fractionation under reduced pressure gives, after a small fore-run, 16.6–20.6 g. (63–78%) of 2-fluoroheptyl acetate, b.p. 83–87° (10 mm.), n25D 1.4101.
B. 2-Fluoroheptanoic acid (Note 2). A 250-ml. two-necked flask is fitted with a thermometer and a condenser that has an outlet tube to carry oxides of nitrogen to a gas absorption trap3 or the back of a hood. It is charged with 17.6 g. (0.100 mole) of 2-fluoroheptyl acetate, 50 ml. of glacial acetic acid, and 60 ml. of 16 N nitric acid. The mixture is heated at 48–50° for 25 hours by means of an electric heating mantle. It is diluted with 500 ml. of water and crushed ice and extracted with one 300-ml. portion and five 100-ml. portions of ether (Note 3). The combined ether extracts are added carefully to a slurry of 125 g. of sodium bicarbonate in 500 ml. of water in a 2-l. beaker. The aqueous alkaline solution is extracted with two 100-ml. portions of ether, which are discarded. The aqueous solution is neutralized to a pH of approximately 4 with about 300 ml. of 10% hydrochloric acid and is extracted with one 300-ml. portion and five 100-ml. portions of ether. The combined extracts are washed with four 100-ml. portions of water to remove traces of acetic acid and dried over anhydrous sodium sulfate. The ether is removed by distillation, leaving 12–13.5 g. of crude 2-fluoroheptanoic acid that soon solidifies. It is purified by distillation under reduced pressure through a short Claisen still-head with a short condenser that can be heated by steam, a burner, or a heat lamp when the acid solidifies in it. 2-Fluoroheptanoic acid, b.p. 62–64° (0.15 mm.), 78–80° (0.7 mm.), is obtained as a moist, waxy, pale yellow solid that smells faintly of acetic acid. After being dried on a porous plate, it is odorless and nearly colorless; weight 11.5–12.5 g. (78–84%), m.p. 38–39°.
2. Notes
1. Thorough washing with water is necessary to remove residual dimethylformamide.
2. 2-Fluoroheptanoic acid required no more than the usual precautions accorded organic compounds, for it and its precursors have LD50>100 mg./kg. in mice. The relatively low toxicity of this and other 2-fluoroalkanoic acids is in contrast to the high toxicity of the ω-fluoro acids F(CH2)nCOOH with n an odd number (if n = 5, LD50 = 1.3 mg./kg. in mice).4
3. The solubility of the fluoro acid in water is sufficient to require thorough ether extraction.
3. Discussion
2-Fluoroheptanoic acid5 has been prepared only by the present procedure.
4. Merits of the Preparation
Bromofluorination2 followed by the present procedure is a general way to convert 1-alkenes to 2-fluoroalkanoic acids; similar results have been obtained with ethylene, propylene, 1-butene, 1-hexene, 1-octene, 1-decene, and methyl 10-undecenoate.5 It is an easy and convenient way to make 2-fluoroalkanoic acids, for it requires only conventional apparatus and readily available intermediates.
This preparation is referenced from:

References and Notes
  1. Department of Chemistry, University of Western Ontario, London, Ontario, Canada.
  2. F. H. Dean, J. H. Amin, and F. L. M. Pattison, this volume, p. 136.
  3. C. F. H. Allen, Org. Syntheses, Coll. Vol. 2, 4 (1943).
  4. F. L. M. Pattison, S. B. D. Hunt, and J. B. Stothers, J. Org. Chem., 21, 883 (1956).
  5. F. L. M. Pattison, R. L. Buchanan, and F. H. Dean, Can. J. Chem., 43, 1700 (1965).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

oxides of nitrogen

hydrochloric acid (7647-01-0)

acetic acid (64-19-7)

ether (60-29-7)

sodium acetate (127-09-3)

sodium bicarbonate (144-55-8)

propylene (115-07-1)

nitric acid (7697-37-2)

sodium sulfate (7757-82-6)

calcium sulfate (7778-18-9)

ethylene (9002-88-4)

1-butene (106-98-9)

sodium iodide (7681-82-5)

dimethylformamide (68-12-2)

1-hexene (592-41-6)

1-Bromo-2-fluoroheptane (1786-32-9)

2-Fluoroheptanoic acid,
Heptanoic acid, 2-fluoro- (1578-58-1)

2-Fluoroheptyl acetate (1786-44-3)

methyl 10-undecenoate (111-81-9)

1-octene (111-66-0)

1-decene (872-05-9)