A. Bromoacetic acid. (Note 1). A mixture of 1 l. (17.5 moles, excess) of glacial acetic acid, 200ml. of acetic anhydride, and 1 ml. of pyridine is placed in a 3-l. flask fitted with a dropping funnel and a reflux condenser, the end of which is protected with a drying tube (Note 2); the tip of the dropping funnel should reach below the level of the liquid. Some glass beads are added, and the mixture is heated to boiling. The flame is then removed, approximately 1 ml. of bromine is added, and the reaction is allowed to proceed until the liquid becomes colorless (Note 3). Then the remainder of 1124 g. (360 ml., 7.03 moles) of bromine (Note 4) is added as rapidly as it will react (Note 5); during this period (about 2.5 hours), the acid is kept boiling gently by means of a flame. After about half the bromine has been added, the liquid assumes a cherry color which is retained throughout the remainder of the bromination. After all the bromine has been added, the mixture is heated until it becomes colorless.

The mixture is allowed to cool, and 75 ml. of water is added slowly to destroy the acetic anhydride. Excess acetic acid and water are now removed on a boiling water bath under a pressure of approximately 35 mm. When the evaporation is complete, the residue will crystallize on cooling; this residue, which is almost pure bromoacetic acid, weighs 845–895 g. (Note 6).

B. Ethyl bromoacetate. For the esterification, an apparatus similar to that used in the preparation of anhydrous oxalic acid [Org. Syntheses, Coll. Vol. 1, 422 (1941)] may be used, but with the outlets from the trap reversed so that the lighter liquid returns to the mixture and the heavier liquid (water) is drawn off at the bottom. A somewhat simpler apparatus may be built using the water trap shown in Fig. 12 (Note 7). The crude bromoacetic acid is placed in a 3-l. flask, together with 610 ml. of ethanol (9.9 moles, excess) and 950 ml. of benzene. About 1.5 ml. of concentrated sulfuric acid is added to hasten the reaction (Note 8), and the mixture is refluxed on a boiling water bath while the water is separated and measured. Approximately 296 ml. of liquid (whose composition is approximately 50% ethanol and water) separates from the benzene; this includes all the water formed in the reaction, together with the excess ethanol. When no more water separates from the benzene, 75 ml. of ethanol is added to the reaction mixture and heating is continued for 30 minutes. If the reaction has been completed, there will not be a second phase in the distillate. The end of the reaction is also indicated when the benzene flowing through the side tube becomes clear and the rate of refluxing decreases considerably. At this point, 150 ml. of benzene is condensed and removed through the trap.

The mixture is transferred to a separatory funnel and washed once with 1.5 l. of water, once with 1.5 l. of 1% sodium bicarbonate solution, and finally with 1.5 l. of water. It is then dried over anhydrous sodium sulfate and fractionated at atmospheric pressure from an oil bath using a Vigreux column 1 ft. in length (Note 9). The fraction boiling at 154–155°/759 mm. is collected (Note 10). The yield is approximately 818 g. (65–70%).