Diethyl succinate, reaction with sodium

Diethyl succinate, reaction with sodium ethoxide, 46, 25... 

The condensation of aldehydes and ketones with succinic esters in the presence of sodium ethoxide is known as the Stobbe condensation. The reaction with sodium ethoxide is comparatively slow and a httlo reduction of the ketonic compound to the carbinol usually occurs a shorter reaction time and a better yield is generally obtained with the more powerful condensing agent potassium ieri.-butoxide or with sodium hydride. Thus benzophenone condenses with diethyl succinate in the presence of potassium [Pg.919]

Sodium azide, reaction with l butyl chloroacetate, 46, 47 reaction with diazomum salt from o amino-f> -ni trobiphcny L, 46, 86 Sodium chlorodifluoroacetate, 47, SO reaction with tnphenylphosphme and benzaldehyde, 47, SO Sodium ethoxide, 46, 2S reaction with diethyl succinate, 46,2S Sodium formate as reducing agent in preparation of palladium catalyst, 46, 90... 

Succinic esters condense with aldehydes and ketones in the presence of bases, eg, sodium alkoxide or piperidine, to form monoesters of alkybdenesuccinic acids, eg, condensation of diethyl succinate with acetone yields ethyl 2-isopropyhdenesuccinate (eq. 3). This reaction, known as Stobbe condensation, is specific for succinic esters and substituted succinic esters (98,99). 

Method 2. In the apparatus described above is placed 4.8-5.0g. ( 0.2 g.-atorn) of clean sodium and 8.0-8.2 g. ( 0.2 g.-atom) of clean potassium (Ilotes 3, 4). The flask is heated with a heat gun to form the low-melting alloy, and then 300-350 ml. of anhydrous ether is added from a freshly opened can. The stirrer is operated at full speed until the alloy is dispersed and then at a slower speed for the remainder of the reaction (Notes 5, 6). A mixture of 17.4 g. (0.1 mole) of diethyl succinate (Note 7), 44g. (0.4 mole) of chlorotrimethylsilane (Note 8), and 125 ml. of anhydrous ether is then added at a rate sufficient to keep the reaction under control (Note 14). The purple mixture is stirred for another 4-6 hours (Note 9) and then filtered and washed as above in a nitrogen dry-box (Note ll). The product is distilled as above forerun 0.5-2 g. to 80° (10 mm.) and then at 82-86° (10 mm.) as a colorless liquid, 13.8-16.1 g. (60-70%), 1.4323-1.4330 (Notes 15-19). 

I. 2,5-Dicarbethoxy-1,4-cyclohexanedione (7) A 500-ml, three-necked, round-bottom flask is fitted with a condenser (drying tube) and arranged for magnetic stirring. A solution of sodium ethoxide is prepared in the flask by the addition of sodium (9.2 g, 0.4 g-atom) in small pieces to 90 ml of absolute ethanol. The mixture is heated at reflux for 3 hours (oil bath) to complete the reaction. Diethyl succinate (34.8 g, 0.2 mole) is added to the hot solution in one portion exothermic ) and the mixture is refluxed for 24 hours. (A pink precipitate forms and persists during the reflux.)... 

Sodium ethoxide, 46, 2S reaction with diethyl succinate, 46,25... 

Commercial absolute ethanol is dried by heating with sodium and diethyl succinate and is then distilled directly into the reaction flask. 

A. Z,5-DicaThelhoxy-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 Caution 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. 

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. 

CH2,CH2,C02Et. From the latter the three-carbon unit of diethyl succinate may be recognised, and the Stobbe condensation is a suitable illustration of this process. Thus the reaction of aldehydes or ketones with succinic esters in the presence of potassium t-butoxide (or with sodium hydride) gives alkylidene-succinic acid esters (25). The reaction is somewhat slower in the case of the less basic sodium ethoxide. 

An efficient synthesis of the 7-deoxy zaragozic acid core was deveioped by M.A. Calter and co-workers. The assembly of this complex structure was based on the interrupted Feist-Benary reaction, which produces highiy oxygenated dihydrofuranols that can be isolated. To this end, the sodium enolate of malondialdehyde was reacted with 2-bromo-3-oxo-diethyl succinate in benzene at room temperature to afford 29% of the c/s-dihydrofuranol. This product was converted to the zaragozic acid core in four steps. 

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