A. Ethyl hydrazodicarboxylate. In a 3-l., three-necked flask equipped with a mechanical stirrer, two 500-ml. dropping funnels, and a thermometer (Note 1), is placed a solution of 75 g. (1.5 moles) of 100% hydrazine hydrate (or 88.5 g. of 85% hydrazine hydrate) in 750 ml. of 95% ethanol. The reaction flask is cooled in an ice bath. When the solution temperature drops to 10°, 326 g. (3 moles) of ethyl chloroformate is added dropwise with stirring at a rate sufficient to maintain the temperature between 15° and 20°. After exactly one-half of the ethyl chloroformate has been introduced, a solution of 159 g. (1.5 moles) of sodium carbonate in 750 ml. of water is added dropwise simultaneously with the remaining ethyl chloroformate. The addition of these two reactants is regulated so that the temperature does not rise above 20°. The addition of the chloroformate should be completed slightly in advance of the sodium carbonate, thus maintaining an excess of the chloroformate in the solution at all times. During the course of the addition of the reagents, a precipitate is formed.

After addition of the reactants is complete, the walls of the flask are washed down with 200 ml. of cold water, and the reaction mixture is allowed to stir for 30 minutes. The precipitate is then collected on a Büchner funnel, washed well with a total of 1 l. of cold water, and dried in a vacuum oven at 80°. There is obtained 215–225 g. (81–85%) of ethyl hydrazodicarboxylate which melts at 131–133°. It is sufficiently pure for the preparation of ethyl azodicarboxylate (Note 2) and (Note 3).

B. Ethyl azodicarboxylate. Caution! Both ethyl and methyl azodicarboxylate are sensitive to heat. Thus, in a sealed capillary they explode violently when heated by a flame. Overheating is to be avoided, and distillations should be from a bath, not an electrically heated mantle. Distillations should be well shielded. Since copious fumes of nitrogen oxides are evolved during the oxidation by nitric acid, this operation and the subsequent work-up should be carried out in an efficient hood.

A mixture of 200 g. of ethyl hydrazodicarboxylate in 125 ml. of 70% nitric acid is placed in a 1-l., three-necked flask equipped with a mechanical stirrer, gas-outlet tube, and thermometer. The flask is cooled in an ice bath, and, when the temperature of the solution reaches 5°, 220 ml. of ice-cold yellow fuming nitric acid (90–95% HNO₃, d₁₅ = 1.49–1.50) is added. The reaction mixture is maintained at 0–5° for 2 hours with stirring and is then carefully poured on a stirred mixture of 500 g. of ice, 500 ml. of ice water, and 100 ml. of methylene chloride in a 2-l. beaker placed in a metal pan (Note 4). After the ice melts, the solution is transferred carefully to a 2-l. separatory funnel. The organic (lower) layer is removed, and the acid layer is extracted (Note 5) with three 100-ml. portions of methylene chloride. The combined organic layers are washed twice with 100-ml. portions of ice water and are then stirred mechanically for 10 minutes with 500 ml. of ice-cold 10% potassium bicarbonate solution. The layers are separated in a separatory funnel, and the organic layer is finally washed with 100 ml. of ice water and dried quickly with a small portion of anhydrous magnesium sulfate that is removed by filtration. The solution is dried overnight with a fresh portion of anhydrous magnesium sulfate. Caution! The following distillations should be well shielded. The methylene chloride is removed on a steam bath under reduced pressure, and the residue is rapidly distilled without fractionation under vacuum (1–5 mm.) from a flask immersed in an oil bath whose temperature is raised gradually from 75° to 130°. The crude distillate is then fractionally distilled under vacuum through a short column packed with glass helices, using an oil bath to heat the distillation flask. After a short fore-run, the main fraction is collected at 93–95°/5 mm. There is obtained 138–158 g. (70–80%) of ethyl azodicarboxylate which freezes at 6° (Note 6), (Note 7), and (Note 8).