A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1955, 35, 15
DOI: 10.15227/orgsyn.035.0015
[Octanoic acid, 2-methyl-3-oxo-, sec-butyl ester]
Submitted by Kenneth L. Rinehart, Jr.1
Checked by John C. Sheehan and J. Iannicelli.
1. Procedure
A 2-l. three-necked round-bottomed flask is fitted with a condenser arranged for distillation, a 200-ml. dropping funnel, and a mercury-sealed mechanical stirrer. Connections are most conveniently made with ground-glass joints, and the flask is heated on a steam cone. Cupric bromide (0.4 g.), 39.2 g. (0.60 g. atom) of freshly sand-papered zinc foil cut into narrow strips, and 1.2 l. of benzene previously dried over sodium are added to the flask. To dry the apparatus and contents, 300 ml. of benzene is slowly distilled from the flask with stirring. Heating is interrupted, and the condenser is quickly arranged for reflux and fitted with a calcium chloride drying tube. To the flask are added rapidly with stirring 38.9 g. (0.40 mole) of n-capronitrile (Note 1) and 125.4 g. (0.60 mole) of sec-butyl α-bromopropionate (Note 2). Refluxing is resumed, and after a 3–5 minute induction period blackening of the zinc surface and clouding of the solution are noted as the first signs of reaction. Heating is maintained a total of 45 minutes, after which the solution is cooled for 15 minutes in an ice bath (Note 3).
To the cooled solution is added with vigorous stirring 400 ml. of ice-cold 12N sulfuric acid. The ice bath is removed, and stirring is continued at room temperature for a total of 2 hours (Note 4). The reaction mixture is poured into a 2-l. separatory funnel; after separation, the aqueous lower layer is drained into a 2-l. separatory funnel containing 800 ml. of water which has been used to wash the reaction flask. The aqueous layer is extracted twice with 200-ml. portions of benzene which have also been employed to rinse the reaction flask. The original organic layer and the combined benzene extracts are kept separate and are washed successively with 400-ml. portions of water, saturated sodium bicarbonate solution, and again with water. The two organic portions are combined and allowed to stand over anhydrous sodium sulfate until clear. The solvent is removed at atmospheric pressure by flash distillation through a fractionating column (Note 5). For this operation, a side-arm distilling flask equipped with a dropping funnel is heated by an oil bath whose temperature is maintained at 140–150°. After all the solvent has been added, the dropping funnel is replaced by a capillary, and the last of the solvent is removed at reduced pressure furnished by a water pump. Finally, an oil pump is attached and the product is fractionated at about 5 mm. pressure (Note 6). After a small fore-run, sec-butyl α-n-caproylpropionate is obtained as a clear liquid; b.p. 112–114°/4.5 mm. (134–136°/12 mm.), n25D 1.4293 (Note 7) and (Note 8). The yield is 46.0–52.9 g. (50–58% based on n-capronitrile) (Note 9).
2. Notes
1. Commercial n-capronitrile (Eastman Kodak white label grade) is distilled through a fractionating column before use; b.p. 161–163°, n25D 1.4052.
2. α-Bromoesters are severe lachrymators, and it is necessary to conduct reactions involving them in a well-ventilated hood. sec-Butyl α-bromopropionate is prepared from commercially available ethyl α-bromopropionate (Sapon Laboratories, Inc., 543 Union Street, Brooklyn 15, New York) by transesterification with sec-butyl alcohol using sulfuric acid catalyst. The product boils at 97–98°/39 mm. and has n25D 1.4420. Darkening of the α-bromoester is prevented by storage over a few drops of mercury.
3. Unreacted zinc usually remains at this point, and the solution is yellow to brown. Most of the color is discharged on subsequent addition of the acid.
4. With 3-methylnonanoicnitrile it is necessary to continue the stirring in sulfuric acid for an additional period; a total of 19 hours is sufficient.
5. A 50 cm. by 8 mm. simple Podbielniak column2 with partial-reflux head is adequate for this and subsequent distillations.
6. Fractionation at higher pressures and temperatures leads to some thermal decomposition of the product.
7. An analytical sample of a redistilled center cut had n25D 1.4302.
8. β-Ketoesters with alkyl substituents in the α-position give a blue-violet color with ferric chloride.3 Copper chelates of the α-alkyl-β-ketoesters could not be isolated. The corresponding 5-pyrazolones, although often difficultly crystallizable, appear to be the most suitable derivatives. The 5-pyrazolone from sec-butyl α-n-caproylpropionate is prepared according to von Auwers and Dersch4 and has a melting point of 80.4–82.9°.
9. This method is suitable for the preparation of mono- and di-α-substituted β-ketoesters. Bromoacetates fail in this reaction. Yields with ethyl α-bromopropionate are considerably lower (30–36% with capronitrile); however, ethyl esters are useful for higher-molecular-weight compounds whose sec-alkyl esters are cracked by distillation. With 3-pentyl α-bromopropionate, the yields are slightly higher (53–60% with capronitrile). Both aromatic and aliphatic nitriles are suitable; benzonitrile gives yields comparable to those obtained with capronitrile. Alkyl substitution in the α- and β-positions (cf. (Note 4)) of aliphatic nitriles lowers the yield to 29% and 38%, respectively; γ-substitution has no effect. Recently it has been shown that a significant improvement in the yields of ketoesters is obtained by the use of a mixture of benzene and ether as a solvent.5
3. Discussion
The procedure is essentially that of Horeau and Jacques6 as modified by Cason, Rinehart, and Thornton.7 The reaction described is that discovered by Blaise8 and is more extensively discussed in the second-named paper. Ethyl α-n-caproylpropionate has been prepared by the alkylation of ethyl n-caproylacetate with methyl iodide in the presence of sodium ethoxide.9 This method would not be expected to yield a pure product owing to contamination with starting ketoester and disubstituted ketoester.

References and Notes
  1. University of California, Berkeley, California.
  2. Podbielniak, Ind. Eng. Chem., Anal. Ed., 3, 177 (1931); 5, 119 (1933).
  3. Henecka, Ber., 81, 188 (1948).
  4. von Auwers and Dersch, Ann., 462, 115 (1928).
  5. Cason and Fessenden, J. Org. Chem., 22, 1326 (1957).
  6. Horeau and Jacques, Bull. soc. chim. France, 1947, 58.
  7. Cason, Rinehart, and Thornton, J. Org. Chem., 18, 1594 (1953).
  8. Blaise, Compt. rend., 132, 478, 978 (1901); Blaise and Courtot, Bull. soc. chim. France, [3] 35, 599 (1906).
  9. Locquin, Bull. soc. chim. France, [3] 31, 596 (1904).

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

sulfuric acid (7664-93-9)

Benzene (71-43-2)

ether (60-29-7)

benzonitrile (100-47-0)

sodium bicarbonate (144-55-8)

sodium sulfate (7757-82-6)

mercury (7439-97-6)

zinc (7440-66-6)

sodium (13966-32-0)

sodium ethoxide (141-52-6)

ferric chloride (7705-08-0)

Methyl iodide (74-88-4)

ethyl α-bromopropionate (535-11-5)

cupric bromide (7789-45-9)

n-capronitrile (628-73-9)

Octanoic acid, 2-methyl-3-oxo-, sec-butyl ester,
sec-BUTYL α-n-CAPROYLPROPIONATE (53663-40-4)



3-pentyl α-bromopropionate

sec-butyl alcohol (78-92-2)

sec-butyl α-bromopropionate (22710-17-4)

Ethyl α-n-caproylpropionate

ethyl n-caproylacetate