2.5- Dicarbethoxy-l,4-cyclohexanedione

The utility of base catalyzed condensations of esters to give jS-ketoesters is well known. A straightforward example of this reaction is the intermolecular cyclization of diethyl succinate giving 2,5-dicarbethoxy-l,4-cyclohexanedione, which can in turn be easily decarboxylated to give 1,4-cyclohexanedione. 

At the conclusion of the reflux period, ethanol is removed on a rotary evaporator. Sulfuric acid (200 ml of 2 A solution) is added to the residue, and the mixture is stirred for 3-4 hours. The solid product is collected by filtration, washed with several portions of water, and allowed to dry in the air. It is then dissolved in 150 ml of boiling ethyl acetate, then filtered hot. The filtrate is cooled in ice, affording 16-17 g of 2,5-dicarbethoxy-l,4-cyclohexanedione, mp 126-129° as off-white crystals. 

Cyclohexanedione (5) 2,5-Dicarbethoxy-l,4-cyclohexanedione (10 g) is suspended in a solution of 34 g of 85 % phosphoric acid, 250 ml of water, and 5 ml of ethanol in a 500-ml round-bottom flask. The mixture is refluxed for 5 days (or until all the solid material has dissolved), cooled, and extracted six times with 100-ml portions of chloroform (or better, continuously extracted with chloroform). The combined chloroform extracts are dried (sodium sulfate) and the solvent is removed (rotary evaporator). The residue on distillation affords 1,4-cyclohexanedione, bp 130-133720 mm. The product solidifies and may be recrystallized from carbon tetrachloride, mp 11-19°. 

B. 1,4-Cyclohexanedione. The purified 2,5-dicarbethoxy-l,4-cyclohexanedione (170 g., 0.66 mole) (Note 5) and 170 ml. of water are placed in a glass liner (vented) of a steel pressure vessel of 1.5-1. capacity (fitted with a pressure-release valve). The vessel is sealed, heated as rapidly as possible to 185-195°, and kept at this temperature for 10-15 minutes (Note 6). The reaction vessel is immediately removed from the heater, placed in a large tub of ice water, and cooled to room temperature. The gas pressure then is carefully released. The resulting yellow to orange liquid is transferred to a distillation flask with the aid of a minimum volume of ethanol, and most of the water and ethanol is removed under reduced pressure by means of a rotary evaporator. The flask is attached to a short heated column fitted with a short air condenser. The remainder of the water and ethanol is removed under reduced pressure, and the 1,4-cyclohexanedione is distilled, b.p, 130-133° (20 mm.). The product solidifies to a white to pale-yellow solid, m.p. 77-79°, deld 60-66 g. (81-89% yield from 2,5-dicarbethoxy-l,4-cyclohexanedione). The compound may be conveniently recrystallized from carbon tetrachloride (7 ml. per gram of dione) the purified product is obtained as white plates, m.p. 77-79° (90% recovery). 

Dicarbethoxy-l,4-cyclohexanedione has been prepared by the self-condensation of diethyl succinate by use of sodium or sodixim ethoxide catalyst (with or without a solvent) and by reaction of ethyl 4-bromo-3-ketobutanoate or ethyl 4-chloro-3-ketobutanoate with sodium ethoxide in ethanol. 

Cyclohexanedione has been prepared by hydrolysis and decarboxylation of 2,5-dicarbethoxy-l,4-cyclohexanedione by using concentrated sulfuric acid, aqueous alcoholic phosphoric acid, or water at 195-200°, and by peroxyvanadic acid oxidation of cyclohexanone. 

Hydrolysis, of 2,5-dicarbethoxy-l,4-cyclohexanedione to 1,4-cyclo-hexanedione, 45, 2S of 7,7-dimethoxybicyclo[2.2.1]hep-tene, 48,2S... 

A. 2,5-Dicarbethoxy-l,4-cyclohexanedione. A solution of sodium ethoxide is prepared by adding small pieces of sodium (92 g., 4 g. atoms) as rapidly as possible to 900 ml. of commercial absolute ethanol contained in a 3-1., three-necked, round-bottomed flask equipped with two stoppers and a reflux condenser fitted with a drying tube packed with calcium chloride and soda lime. The reaction is completed by heating the mixture under reflux for 3-4 hours (Note 1). To the hot solution is added diethyl succinate (348.4 g., 2 moles) (Note 2) in one portion (1CautionI Exothermic reaction), and the mixture is heated under reflux by maintaining the original bath temperature for 24 hours. A thick pink-colored precipitate is formed almost immediately and remains throughout the reaction. 

Hydrolysis, of 2-benzyl-2-carbometh-oxycyclopentanone with lithium iodide in 2,4,6-collidine, 46, 7 of 7-butyrolactone to ethyl y-bromo-butyrate with hydrogen bromide and ethanol, 45, 42 of 2,5-dicarbethoxy-l,4-cyclohexane-dione to 1,4-cyclohexanedione, 45,25... 

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