Guareschi imide

Guareschi imides are useful synthetic intermediates. They are formed from a ketone reacting with two equivalents of the cyanoacetic esters and ammonia. This transformation is illustrated in the formation of 4,4-dimethylcyclopentenone 30.The synthesis was initiated with the Guareschi reaction of 3-pentanone 27 with 28 to generate imide 29. This product was hydrolyzed to the diacid and esterified. Cyclization of the diester via acyloin condensation followed by hydrolysis and dehydration afforded the desired target 30. 

Spiro[5.5]undecan-3-one (33.2 g, 0.2 mol) and 47.5 g ethyl cyanoacetate (0.42 mol) were placed in a 500-mL thick-walled flask. The mixture was cooled to 0°C, and 100 mL ethanol saturated with anhydrous ammonia at 0°C was added. A stopper was wedged and the mixture was stored at 0-5°C for 1 week. The precipitated ammonium salt of the Guareschi imide was filtered, dissolved in boiling water. Altered, and acidified with HCI. The Guareschi imide was filtered, washed with water, and dried. It melted at 230-233°C and 232-233°C after recrystaUization from alcohol-water. l,5-Dicyano-3-azadispiro[5.2.5.2] hexadecane-2,4-dione (24 g) was obtained, in a yield of 40%. 

The above is an example of the Guareschi reaction. It is applicable to most dialkyl ketones and to alicyclic ketones (e.g., cyclohexanone, cyc/opentanone, etc.). The condensation product (I) is probably formed by a simple Knoe-venagel reaction of the ketone and ethyl cyanoacetate to yield ethyl a-cyano-pp dimethylacrylate (CH3)2C=C(CN)COOCjHj, followed by a Michael ad tion of a second molecule of ethyl cyanoacetate finally, the carbethoxyl groups are converted to the cyclic imide structure by the action of ammonia. 

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