Isoxazoles forming 1,2,4-thiadiazoles

Addition of nucleophiles to the cyano group of cyanothiadiazole under basic conditions takes place with unusual ease <88AG(E)434,94ACS372). Hydrolysis to the amide, for example, can be effected at 0°C in the presence of a catalytic amount of sodium hydroxide or basic ion-exchange resin. At reflux temperature, hydrazine and monosubstituted hydrazines convert 3,4-dicyano-l,2,5-thia-diazole into the l,2,5-thiadiazole[3,4-. The base-catalyzed addition of acetone to cyanothiadiazole forms an enamino ketone, used as a key intermediate for the synthesis of a number of heterocyclic ring systems, e.g. isothiazole, isoxazole, pyrazole, pyrimidine, and thiazole <77H(6)1985>. 

Oxadiazoles are difficult to alkylate. However, N-methylfurazinium salts are formed on heating furazans with dimethyl sulfate (74AJC1917,95JCS(P1)1083) the reaction is approximately 7 and 62 times slower, respectively, than the corresponding methylations of 1,2,5-thiadiazole and isoxazole. The N-ethyl salts of furazan itself and 3-phenylfurazan have been prepared using triethyloxonium tetrafluoroborate (64JA1863). 

It has been found [131] that mononitrobenzazoles 155 (4- and 5-nitrobenzofurazans, -thiadiazoles, -selenadiazoles, and -[c]isoxazoles) are able to form cycloadducts 156 with N-methyl azomethine ylide 153 (Scheme 76). This dipole adds only at the C=C bond activated by the nitro group, thus giving tetrahydroisoindoles condensed with azoles. 

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