1, 4-Cyclohexanedione

Submitted by Arnold T. Nielsen and Wayne R. Carpenter1 Checked by W illiam G. Dauben and E. John Deviny 

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. 

At the end of the 24-hour period, the ethanol is removed under reduced pressure on a steam bath. A 2N sulfuric acid solution (2 1.) is added to the warm residue, and the mixture is stirred vigorously for 3-4 hours (Note 3). The solid is removed by suction filtration and washed several times with water. The air-dried product is a pale-buff powder weighing 180-190 g., m.p. 126-128°. The solid is added to 1.5 1. of ethyl acetate, the mix- 

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°, yield 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). 

The diethyl succinate was obtained from Eastman Organic Chemicals and used without purification. 

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When active methylene compounds are used as nucleophiles in carbonyla-tion at 50 °C and I atm, ketones are obtained. As an example, the reaction of l,3-cyclohexanedione affords the trione 32(17],... 

Conjugation is more important 1 3 Cyclohexanedione exists mainly in its enol form in spite of the fact that intramolecular hydrogen bonding is impossible due to the distance between the carbonyl group and the enohc —OH group... 

Another interesting structure with a high degree of ring character along the backbone is the product obtained by the reaction of 1,4-cyclohexanedione [XIV] and pentaerythritol [XV] ... 

Acceptors. Most common acceptor molecules such as tetracyanoethylene or tetracyanoqurno dime thane ate commercially available. However, TCNQ can be synthesized in high yield by a two-step synthesis involving a condensation of malonitrile with 1,4-cyclohexanedione followed by treatment with an oxidizing agent such as bromine or A-bromosuccinamide in pyridine solvent (23) (Fig. 6). 

Acetaldehyde can be isolated and identified by the characteristic melting points of the crystalline compounds formed with hydrazines, semicarbazides, etc these derivatives of aldehydes can be separated by paper and column chromatography (104,113). Acetaldehyde has been separated quantitatively from other carbonyl compounds on an ion-exchange resin in the bisulfite form the aldehyde is then eluted from the column with a solution of sodium chloride (114). In larger quantities, acetaldehyde may be isolated by passing the vapor into ether, then saturating with dry ammonia acetaldehyde—ammonia crystallizes from the solution. Reactions with bisulfite, hydrazines, oximes, semicarb azides, and 5,5-dimethyl-1,3-cyclohexanedione [126-81 -8] (dimedone) have also been used to isolate acetaldehyde from various solutions. 

Tetracyanoquinodimethane [1518-16-7] (5), 2,2 -(2,5-cyclohexadiene-l,4-diyhdene)bispropanedinitrile (TCNQ), is prepared by condensation of 1,4-cyclohexanedione with malononittile to give l,4-bis(dicyanomethylene)cyclohexane [1518-15-6] which is oxidized with bromine (31). 

There are several laboratory methods useful for the preparation of suberic acid. One starting material is 1,6-hexanediol which can be converted to the dibromide with HBr. Reaction of the dibromide with NaCN gives the dinitrile which can be hydrolyzed to suberic acid. The overall yield is 76% (42). Another laboratory method is the condensation of 1,3-cyclohexanedione with ethyl bromoacetate foUowed by reductive cleavage to give suberic acid in 50% yield (43). 

Cyclohexanedione monoethylene acetal (l,4-dioxa-spiro[4.5]decan-8-one) [4746-97-8] M 156.2, m 70-73", 73.5-74.5". Recrystd from pet ether and sublimes slowly on attempted distillation. Also purified by dissolving in Et20 and adding pet ether (b 60-80°) until turbid and cool. [Gardner et al. J Am Chem Soc 22 1206 I957 Britten and Lockwood J Chem Soc Perkin Trans I 1824 1974.]... 

ALKYLATION OF DIMEDONE WITH A TRICARBONYL(DIENE)IRON COMPLEX TRlCARBONYL[2-[(2,3,4,5-t))-4-METHOXY 2,4 CYCLOHEXADUEN-l-YLJ-5,5-DIMETHYL-l,3-CYCLOHEXANEDIONE]IRON... 

The procedure described is essentially that of Belleau and Weinberg and represents the only known way of obtaining the title compound. One other quinone acetal, 1,4,9,12-t6traoxadispiro[4.2.4.2]tetradeea-6,13-diene, has been synthesized by a conventional method (reaction of 1,4-cyclohexanedione with ethylene glycol followed by bromination and dehydrobromination ) as well as by an electrochemical method (anodic oxidation of 2,2-(l,4-phenylenedioxy)diethanol ). Quinone acetals have been used as intermediates in the synthesis of 4,4-dimethoxy-2,5-cyclohexadienone,. syw-bishomoquinone, - and compounds related to natural products. ... 

Enamines of cyclic ketones react similarly (68,131). Thus the enamine (28) gave a goodyield of the monophenylhydrazone of 1,2-cyclohexanedione (193) on reaction with phenyldiazonium fluoborate and subsequent hydrolysis (6S). The products (193) have been cyclized to the corresponding... 

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