A mixture of 1 mole of alkyl or aryl cyanide and 1 mole of hydroxylamme hydrochloride was dissolved in 500 ml of 80% aqueous ethanol. One-half mole of K2CO3 was added, and following the evolution of CO» the solution was heated under reflux overnight. The solvent was removed under reduced pressure (steam bath), and the residue was twice extracted with 200 ml of absolute ethanol. The ethanol extract was concentrated to dryness, and the resulting amidoxime was recrystallized from benzene. Unless otherwise indicated, the amidoximes used are described in ref 2b.3-Substituted 1,2,4-Oxadiazoles (Table I). General Procedure.-A mixture of 0.1 mole of appropriate amidoxime and 100 ml of triethyl orthoformate was heated under reflux for 2 hr, and the reaction mixture was then distilled under reduced pressure.If the product was a solid at room temperature, it was recrystallized from ethyl acetate-petroleum ether (60-70°) mixture. The nitrile corresponding to the starting material for the amidoxime was often a by-product of the reaction.® 3-p-Chlorophenyl-l,2,4-oxadiazoIe ( 14).-To 0.1 mole of DMF-POCh complex10 was added, with stirring, an ether solution of 0.05 mole of p-chlorobenzamidoxime. The temperature was maintained near 10°b y means of an ice bath and the mixture was stirred for 10 min. After the solvent was removed at 60°, (14) Melting points were taken with a Fisher-Johns apparatus and are uncorrected.the residue was washed twice with 150 ml of ice water. The product was recrvstallized from methanol and gave 14, mp 100-102°, in 80%. yield.3,5-Disubstltuted 4,5-Dihydro-1,2,4-oxadiazoles (Table IV).(a) General Procedure.-To 0.1 mole of appropriate amidoxime dissolved in 200 ml of 50% aqueous ethanol was added portionwise 0.15 mole of aldehyde. After the initial exothermic reaction had ended, the solution was allowed to stand at room temperature for 2 days and then was concentrated under reduced pressure (steam bath). The residue was recrystallized from ethanolwater if it was a solid, or was distilled using a spinning-band column if it was a liquid at room temperature. (b) Spiro-4,5-dihydro-l,2,4-oxadiazoles (Table IV).-A mixture of 0.05 mole of the appropriate amidoxime and 20 ml of cyclohexanone15 was heated under reflux for 2 hr. The mixture was concentrated under reduced pressure (steam bath) and the product was recrystallized from benzene.16 Acknowledgment.-The microanalyse.s were determined by W. L. Brown and associates, and D. O. Woolf, Jr., made the physical measurements.
