Diethyl propionylsuccinate

A. Diethyl propionylsuccinate (1). A solution of 412 g. (2.4 mole) of diethyl maleate (Note 1), 278 g. (4.8 mole) of freshly distilled propionaldehyde (Note 2), and 1.2 g. (0.0048 mole) of benzoyl peroxide in a normal 2-1. Pyrex flask is heated under reflux while undergoing irradiation with an ultraviolet lamp (Note 3). The initial reflux temperature is 60°. After 2 hours another 1.2 g. (0.0048 mole) of benzoyl peroxide is added. Strong reflux and irradiation are maintained throughout the entire reaction period. After 18 hours total time, the internal pot temperature reaches 68°. At this point the last 1.2 g. (0.0048 mole) of benzoyl peroxide is added, and the reaction is continued for a total of 30 hours, at which time the pot temperature reaches 74.5°. The reflux condenser is then replaced by a distillation head. The excess propionaldehyde (119 g.) is distilled under atmospheric pressure, b.p. 48-49°. Succinate 1 is distilled under reduced pressure. The main fraction, b.p. 145-151.5° (15-16 mm), provides 417-449 g. (75-81%) of product having sufficient purity for use in the next step (Note 4). 

Diethyl propionylsuccinate Succinic Acid, propionyl-, diethyl ester (8) Butanedioic Acid, 1-oxopropyl-, diethyl ester (9) (41117-76-4)... 

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... 

Diethyl phosphonate, 58, 134, 135, 138 Diethyl propionylsuccinate, 58, 80 82, 85 Diethyl succinate, 57, 1 Diethyl succinates, acylated, 58, 81 Diethyl sulfate, 56, 48 DIETHYL fnzHS-4-TRIMETHYLSILYL-OXY-4-CYCLOHEXENE-1,2-DICAR-BOXYLATE, 58, 163, 164, 167... 

Cyclopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcyclopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsuccinate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic add or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

A stirred mixture of diethyl propionylsuccinate and boric acid heated to 150° during 1 hr. with distillation of mostly ethanol, then the temp, raised to 170° until COg-evolution almost ceases after 1.5 hrs. -> ethyl 4-oxohexanoate. Y 77%. F. e. s. P. A. Wehrli and V. Chu, J. Org. Chem. 38, 3436 (1973). 

The lactone (154) has also been obtained by the Grignard reaction of 6-bromo-2-methoxynaph-thalene with diethyl a-methyl-a-propionylsuccinate [270],... 

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See also in sourсe #XX -- [ , , , ]

See also in sourсe #XX -- [ , , , ]

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