1.2.3- Thiadiazole 4- carboxylic acid, ring synthesis

The pronounced electron-withdrawing nature of the 1,2,5-thiadiazole system is also evidenced by strong carbonyl electrophilic activation and by enhancement of carboxy acidity. The acid dissociation constants of thiadiazole acids, discussed in Section 4.09.4.1, fall in the range 1.5-2.5. The 1,2,3-thiadiazole carboxylic acids are easily decarboxylated at 160-200 °C. This reaction has been used for the synthesis of monosubstituted derivatives as well as the parent ring and deuterated derivatives <68AHC(9)107>. An efficient bromo-decarboxylation of 3-amino-1,2,5-thiadiazole-carboxylic acid has also been reported <70BRP1190359>. 

The modified cephalosporin ceftobiprole (31-8), yet another compound that contains a double bond at the ring carbon, though in this case with a rather complex extended side chain, has shown activity in the clinic against some strains of multidrug resistant bacteria. The synthesis starts with the weU-precedented acylation of the cephalosporin (31-2), available in several steps from the commercially available 7-acetoxy cephalosporanic acid, with the activated thiadiazole carboxylic acid (31-1). The hydroxyl group in the product (31-3) is then oxidized with manganese dioxide to afford the corresponding aldehyde (31-4). This product is then condensed with the fcw-pyrrolidyl phosphonium salt (31-5), itself protected with the... 

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