1.3.4- Thiadiazole, base-catalyzed

The base-catalyzed fragmentation of 4-alkyl-l,2,3-thiadiazoles is a useful method for the preparation of alkyne-1-thiolates <1996T3171>. These alkyne-l-thiolates can then react with carbon disulfide to afford l,3-dithiole-2-thiones. This strategy has been developed to give a synthesis of some novel tetrathiafulvene derivatives <1996T3171>. 

Less common synthetic methods for 1,3,4-thiadiazoles include the oxidative thermal base-catalyzed cyclization of thiosemicarbazido arylates (Equation 40) <2005HAC12> and a tetracyanoethylene (TCNE)-assisted cyclization (Equation 41) <2004ZNB910>. 

Thiadiazole is a planar, thermally stable, and weakly basic aromatic ring system. Aromatic forms of the 1,2,5-thiadiazole nucleus are generally stable to concentrated mineral acids and are only slightly sensitive to base. Base-catalyzed deuterium exchange of the ring protons can be effected... 

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>. 

Analogous base-catalyzed condensations of the 5-imino-A 3-l,2,4-thiadia-zolines (109) with heterocumulenes such as isothiocyanate esters or carbo-diimides (114-116) produce the 1,2,4-thiadiazolidines (117-119), while the addition of nitriles results in the 1,2,4-thiadiazolines (113).98 The structural assignments are in accord with the spectral properties of the products and receive further support from an X-ray analysis of 118b. In this structure, the near identity of the interatomic distances of the linear N—S—N triad, and their difference from the normal N—S value (1.76 A), indicate the existence of no-bond interaction by <7-delocalization. The corresponding molecular dimensions of a structurally comparable true 1,2,4-thiadiazole (120)101 reinforce this interpretation.98... 

A second type of synthetic route to meso-ionic l,3,4-thiadiazol-2-imines (247) is based on the acid-catalyzed reaction of N-thioacylhydrazines (232) with aryl isothiocyanates (Ar-NCS). " This reaction yields the s ts (248) as precursors of the meso-ionic heterocycles (247). An interesting variant upon this route involves the reaction between IV-thioacylhydrazines (232) and acyl isothiocyanates (RCO-NCS). This leads to the meso-ionic heterocycles 247, R = COzEt, CONMej, COMe, COCMe, COAr, and SOjPh. The investigation of these compounds by X-ray photoelectron spectroscopy is a good example of the application of this physical method for the examination of meso-ionic compounds. 

Hydroxythiadiazoles exhibit marked acid properties (see Section 4.26.2.8) and exist essentially in the hydroxy form (68AHC(9)107). Alkylation with alkyl halides or sulfates and base in dipolar aprotic solvents usually forms ethers. In media where the oxygen atom is screened by solvation or by formation of ion pairs, mixtures of N- and O -alkylation products are formed. The reaction of 3-chloro-4-hydroxy-l,2,5-thiadiazole with epichlorohydrin catalyzed by piperidine in the absence of a solvent gave a mixture of N- and O-alkylated products in about equal amounts (72JMC651). Treatment of 3 - hydroxy-4-(A - morpholino) -... 

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