Synthesis Reference(s)

Journal of Medicinal Chemistry, 26, p. 1631, 1983 DOI: 10.1021/jm00365a015Organic Syntheses, Coll. Vol. 1, p. 241, 1941Tetrahedron Letters, 17, p. 3735, 1976 DOI: 10.1016/S0040-4039(00)93096-X

Synthesis

The synthesis of Benzoylformic acid is as follows:Acetophenone (120 g, 1 mol) was dissolved in 2000 ml of pyridine, and 165 g (1.5 mol) of selenium dioxide was added under stirring.The mixture was refluxed for 3 hours and left to cool overnight.Filter through celite, wash the filter cake with xylene, and combine the filtrate and washings with azeotropic evaporation.The evaporated residue was dissolved in 1 L of ethyl acetate and washed with 300 ml of 10% dilute hydrochloric acid.The organic layer was washed with 400 ml of 5% sodium hydroxide solution, and the washed aqueous layer was adjusted to pH 2-3 with 10% dilute hydrochloric acid.A white solid precipitates, is filtered, the filter cake is washed with water, and dried to obtain 120 g of a white solid.Yield: 87%, purity: 99.2%.

Purification Methods

If the sample is oily, then it may contain H2O. In this case dry it in a vacuum desiccator over P2O5 or KOH until crisp. For further purification dissolve 5.5g in hot CCl4 (750mL), add charcoal (2g, this is necessary otherwise the acid may separate as an oil), filter, cool in ice-water until crystallisation is complete. Filter the acid off, and the solvent on the crystals is removed by keeping the acid (4.5g) in a vacuum desiccator for 2 days. Slightly yellow crystals are obtained. It can be recrystallised also from *C6H6/pet ether, and can be distilled in a vacuum. The acid is estimated by titration with standard NaOH. The phenylhydrazone is recrystallised from EtOH, m 163-164o, and the semicarbazone acid has m 259o(dec) (from EtOH). The methyl ester distils at 137o/14mm, 110-111o/2mm, n 20 1.5850. [Baert & Kates J Am Chem Soc 67 1482 1945, Schaffer & Corey J Org Chem 24 1825 1959, Beilstein 10 H 654, 10 IV 2737.]

Definition

ChEBI: A 2-oxo monocarboxylic acid that is glyoxylic acid in which the aldehyde hydrogen is substituted by a phenyl group.