Chemical Reactivity of 1,2,4-Thiadiazole

1,2,4-Thiadiazole is a five-membered, unsaturated, conjugated heteroaromatic, consisting of one sulfur atom and two nitrogen atoms in which one is adjacent to sulfur and the other is one carbon apart in the ring. It is a π-excessive heterocycle but relatively π deficient at carbon atoms. The π electron density at C5 is lowest (0.7888) and therefore nucleophilic substitution is facile at this site. 

The geometry parameters for the 1,2,4-thiadiazole ring revealed that the bond length between N2-C3 (1.317 Å) and N4-C5 (1.313 Å) is an average of single and double bond lengths. However, the bond length between S-N2 (1.649 Å) and C5-S (1.707 Å) has a partial double bond character.

Physical Properties

It is a colorless liquid with an mp of −34°C, a bp of 121°C, and is soluble in water. It is thermally stable.

UV: λmax nm (ε): 229 (3.7).

The chemical shift for C3H appeared at δ 8.66 ppm in 5-phenyl-1,2,4-thiadiazole, while the C5-H proton resonated further downfield at δ 9.9 ppm in 3-phenyl-1,2,4-thiadiazole. This indicated that C5-H is highly deshielded compared to C3-H. A comparative study of the 13C spectra of a variety of 1,2,4-thiadiazoles revealed that generally C3 resonated (δ 148–188 ppm) upfield compared to C5 (δ 161–201 ppm).

Chemical Reactivity

Though 1,2,4-thiadiazole is a π-excessive heterocycle the electron density at both carbon atoms C3 and C5 is low but lowest at C5 due to the presence of two pyridine-like nitrogen atoms. As a result, electrophiles do not attack both the sites but are prone to nucleophilic attack. The electrophiles preferentially attack N4 compared to N2 and form quaternary salts. The parent 1,2,4-thiadiazole is sensitive to acid, alkali, oxidizing, and reducing agents.