3- Methylcyclopentane-l ,2,4-trione

The third group of cyclic compounds formed by intramolecular carbanion addition to the carbonyl group are the target molecules 5,5-dimethylcyclo-hexane-l,3-dione (dimedone, 30) and 3-methylcyclopentane-l,2,4-trione (31). 

Suitable retrosynthetic disconnections of 3-methylcyclopentane-l,2,4-trione may not be immediately obvious owing to the presence of the three carbonyl groups. However, disconnection in the manner shown gives the reagent equivalents diethyl oxalate and butan-2-one. 

Methylcyclopentane-l,2,4-trione, 58, 85 METHYLENECYCLOPROPANE, 57, 36 Methyl ether, chloromethyl-, 55,94 3-Methyl-3-heptyl alcohol, 58, 78 3-Methyl-4-heptyl alcohol, 58, 78 3-Methyl-3-heptyl fluoride, 58, 78 3-Methyl-4-heptyl fluoride, 58, 78 Methyl hydrazinocarboxylate, 58, 103 V-Methylhydroxylamine hydrochloride, 58,... 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

Ketones. - Ylides 47 were produced from the reportedly complex reactions of Ph3P, RO2CC = CCO2R (R = Me, Et, Bu) and 3-chloropentane-2,4-dione, or 5-methylcyclopentane-l,2,4-trione. Vinylketones react with stabilised ylides in polar solvents to produce carboalkoxyphosphoranes 48. " However, if the same reaction is carried out in non-polar solvents then acylphosphorane 49 and an acrylic ester are obtained. It has been reported that the reactions of ketones with stabilised ylides, which are usually unreactive under normal conditions, can be accelerated by microwave irradiation in a domestic microwave oven - without the use of solvents. The advantages of this new route include improved yields and shorter reaction times. 

B. 2-Methylcyclopentane-l, 3,5-trione hydrate. A mixture of 200 g. (0.89 mole) of the keto ester prepared above, 910 ml. of water, and 100 ml. of 85% phosphoric acid is heated under reflux for 4 hours and then cooled in an ice-salt bath to —5°. The trione mixed with oxalic acid separates and is collected by filtration and dried under reduced pressure. The dried material is extracted with boiling ether (250-300 ml.) under reflux, and the ethereal extract is separated from the undissolved oxalic acid. The original aqueous filtrate is also extracted with ether in a continuous extractor. The two extracts are combined, and ether is removed by distillation. The crude trione separates as a dark brown solid and is crystallized from ca. 250 ml. of hot water. The once-crystallized, faintly yellow product weighs 95-105 g. (74-82%), m.p. 70-74°. This product is used in the next step without further purification. A better specimen, m.p. 77-78°, which is almost colorless, can be obtained by recrystallization from hot water after treatment with Norit activated carbon. 

A mixture of 2-butanone and 2.2 moles diethyl oxalate added gradually at 0-5° during 0.5 hr. to a stirred soln. of Na in ahs. ethanol, allowed to warm to room temp, with continued stirring, and refluxed 0.5 hr. crude 2-methyl-4-ethoxalylcyclopentane-l,3,5-trione (Y 53-59%) refluxed 4 hrs. with aq. phosphoric acid crude 2-methylcyclopentane-l,3,5-trione hydrate (Y 74-82%) allowed to react with semicarbazide hydrochloride and Na-acetate in ethanol-water crude 2-methylcyclopentane-l,3,5-trione 5-semicarbazone (Y 60-66%) added at 130° during 30-40 min. to KOH, ethylene glycol, and water, then heated ca. 0.5 hr. at 150° and ca. 2 hrs. at 180-185° 2-methylcyclopentane-1,3-dione (Y 60-67%). J. P. John, S. Swaminathan, and P. S. Venkataramani, Org. Synth. 47, 83 (1967) improved procedure s. Z. G. Hajos, D. R. Parrish, and E. P. Oliveto, Tetrahedron 24, 2039 (1968). 

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