Org. Synth. 1944, 24, 72
DOI: 10.15227/orgsyn.024.0072
[Pyruvic acid, methyl ester]
Submitted by A. Weissberger and C. J. Kibler.
Checked by C. S. Hamilton and R. F. Coles.
1. Procedure
A solution of 88 g. (1 mole) of freshly distilled pyruvic acid,1 128 g. (4 moles) of absolute methanol, 350 ml. of benzene, and 0.2 g. of p-toluenesulfonic acid is placed in a 1-l. round-bottomed flask connected through a ground-glass joint (Note 1) to a methyl ester column shown in Fig. 202 (Note 2). The column is fitted at the top with a cold finger, a thermometer, and an efficient condenser. The solution is refluxed vigorously using an oil bath maintained at 150–155°. The temperature at the top of the column is 59–60°. After refluxing overnight, the liquid in the lower bubbler becomes cloudy and separates into two layers. The lower layer is removed as fast as it is formed (i.e., every 20–30 minutes) throughout the day. Refluxing is continued overnight, and the next morning the lower layer is again removed until cloudiness persists in the upper bubblers (Note 3). The ester is then isolated by fractional distillation of the remaining liquid. The fraction boiling at 136–140° at atmospheric pressure is collected (Note 4). It weighs 66–73 g. (65–71%) (Note 5) and (Note 6).
Fig. 20.
Fig. 20.
2. Notes
1. A ground-glass joint is advisable on account of the long reflux period. Benzene attacks a rubber stopper, and pyruvic acid destroys cork.
2. The Clarke-Rahrs methyl ester column2 is illustrated in Fig. 20. A is the stopcock, above which the aqueous phase collects and is drawn off as necessary. B is a standard-taper ground joint; C is a trap whose outside diameter is 12 mm. At D the space between the consecutive bubblers is shown. E is the thermometer tube, set in at an angle of about 45°; it carries a piece of rubber tubing H which holds the thermometer. F is a solid spot in the top return tube only, where that tube has been sealed off; the apparatus will not function without this seal. It should be pointed out that the upper ends of all the return tubes should terminate just above the bends, as shown at J; otherwise there will be too great a pressure due to the height of the liquid. The overall length as given is not critical.
3. A total of about 300 ml. of liquid will have separated when cloudiness persists in the fourth and fifth bubblers. The liquid collected separates into two layers on cooling. It contains a trace of pyruvic acid.
4. A tarry residue of 10–17 g. is obtained. If an efficient column is not used in the distillation, the fore-runs will contain 5–10 g. of recoverable ester. The yield given is the total yield.
5. The difficulty in the preparation of methyl pyruvate is caused by the fact that this ester is very easily hydrolyzed and that the ester equilibrium is far on the side of the hydrolysis products.
6. Other methyl esters can be made by this procedure.
3. Discussion
Methyl pyruvate has been prepared from the silver salt of pyruvic acid and methyl iodide;3 from the free acid, by the ethanol-vapor method without a catalyst,4 by azeotropic removal of the water produced by the reaction of methanol in the presence of p-toluenesulfonic acid (the present method), and by refluxing with methanol in ethylene dichloride using ethanesulfonic acid as a catalyst (73% yield).5 Pyruvic esters have also been prepared by the catalytic dehydrogenation of lactic acid esters6 and by the oxidation of ethyl lactate with potassium permanganate.7
This preparation is referenced from:

References and Notes
  1. Org. Syntheses Coll. Vol. 1, 475 (1943).
  2. Rahrs, Synthetic Organic Chemicals, Vol. XI, No. 1, The Eastman Kodak Company, February, 1938.
  3. Oppenheim, Ber., 5, 1051 (1872).
  4. Baker and Laufer, J. Chem. Soc., 1937, 1345.
  5. Clinton and Laskowski, J. Am. Chem. Soc., 70, 3135 (1948).
  6. U. S. pat. 1,614,195 [C. A., 21, 746 (1927)].
  7. Org. Syntheses, 31, 59 (1951).

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

Benzene (71-43-2)

methanol (67-56-1)

potassium permanganate (7722-64-7)

ethylene dichloride (107-06-2)

Methyl iodide (74-88-4)

Pyruvic acid (127-17-3)

ethyl lactate (687-47-8)

Methyl pyruvate,
Pyruvic acid, methyl ester (600-22-6)

ethanesulfonic acid (594-45-6)

p-toluenesulfonic acid (104-15-4)

silver salt of pyruvic acid