1.2.3- Thiadiazolo pyrimidines hydrolysis

The fusion of the 1,2,5-thiadiazole system to a heterocyclic nucleus greatly enhances the elec-trophilicity of the substituted ring. These properties are manifested in increased rates of hydrolysis and more facile displacement, Diels-Alder, and cycloaddition reactions. The synthetically useful nucleophilic cleavage of the pyrimidine ring of l,2,5-thiadiazolo[3,4- /]pyrimidines was studied in detail by Shealy and co-workers and previously discussed <68ahc(9)107>. 

The novel derivative 56 (m.p. 127-128 °C) has been prepared in high yield by reaction of the 1,2,5-thiadiazole 55 with thionyl chloride (Scheme 3) <2000JHC1269>. The intermediate 55 is made by alkaline hydrolysis of 4,6-dimethyl[l,2,5]thiadiazolo[3,4-,7 pyrimidine-5,7(4//,6//)-dione 54 <2000JHC1269>. 

Addition of nucleophiles to cyanothiadiazole under basic conditions takes place with unusual ease. 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-1,2,5-thiadiazole into the [l,2,5]thiadiazolo[3,4-d]pyridazines <7iJHC44l>. 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). 

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