3,4-Dicyano-l ,2,5-thiadiazole

DAMN plus SClj or thionyl chloride gives 3,4-dicyano-l,2,5-thiadiazole (143) (61USP2990408 61USP2990409 77GEP(O)2651604). DISN plus SCl ... 

An acyclic NCCN system in which the N-C links may be sp, sp2 or sp3 hybridized reacts with sulfur monochloride or sulfur dichloride to form the appropriate 1,2,5-thiadiazole (68AHC(9)107, 67JOC2823). Thus, diiminosuccinonitrile (384) gives 3,4-dicyano-l,2,5-thiadiazole (385) (72JOC4136). Tables 16 and 17 in CHEC 4.26 list the various substituted systems prepared in this fashion. 

Azole approach. 3,4-Dicyano-l,2,5-thiadiazole with hydrazine yields the 5,7-diamine (751) (71JHC441) in a manner analogous to the reaction of o-phthalonitrile with hydrazine. 

The synthesis of 1,2,5-thiadiazoles from a-diamines was studied as early as 1897 when Michaelis attempted the preparation of the parent compound by reaction of ethylenediamine with sulfur dioxide. The product, however, was bissulfimic acid (28) which readily lost sulfur dioxide to form the betaine (28a). Later Shew reported that 3,4-dicyano-l,2,5-thiadiazole (30) results from the reaction of cis-diaminomaleonitrile (29, HCN tetramer) with thionyl chloride, a reaction which is analogous to 2,1,3-benzothiadiazole formation from o-phenylenediamines. The synthesis of the parent 1,2,5-thiadiazole and some alkyl analogs (32) was accomplished by reaction of salts of... 

DISN reacts with sulfur dichloride to give 3,4-dicyano-l, 2,5-thiadiazole (7), which is readily hydrolyzed to the diacid (8). 

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>. 

Hurd-Mori reaction on hydrazone 147 produced methyl thieno[3,4-r/ -l,2,3-thiadiazole-6-carboxylate 148 along with methyl thieno[3,2-r7 -l,2,3-thiadiazole-5-carboxylate 135 and methyl 5,6-dihydrothieno[3,2-r7 -l,2,3-thiadiazole-5-carboxylate 149 in a ratio of 1 2.6 0.5 (72% combined yield). Conversion of compound 149 to the fully aromatized 135 is accomplished by treatment with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in refluxing benzene for 10 days (Scheme 15). A modified reaction mechanism for the Hurd-Mori reaction is also presented here <1998H(48)259>. 

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