Synthesis of Novel 2,5-Disubstituted 1,3,4-Thiadiazoles: Structural Requirements Necessary for Anticonvulsant Activity

The synthesis of novel 2,5-disubstituted 1,3,4-thiadiazoles and their anticonvulsant activity was analyzed. The synthesis of 1-[5-{(2-methyl-1H- benzimidazol-1-yl)methyl}-1,3,4-thiadiazol-2-yl]-urea involved the dissolution of 5-[(2-methyl-1H-benzimidazol-1-yl)-methyl]-1,3,4-thiadiazol-2-amine in 10 ~ 30 mL of glacial acetic acid diluted to 50 mL with distilled water and to the equimolar (0.01 mol) quantity of sodium cyanate in 20 ~ 30 mL of warm water was added. The precipitates obtained were collected by filtration, washed with cold water and recrystallized from 90% aqueous ethanol. The synthesis of N-[5-(1H-indol-3-yl-methyl)-1,3,4-thiadiazol-2-yl]-hydrazinecarboxamide involved the dissolution of 1-[5-{(2-methyl-1H-benzimidazol-1-yl)methyl}-1,3,4- thiadiazol-2-yl]-urea in 30 ~ 40 mL and to the mixture equimolar solution of hydrazine hydrate in 5 mL of water was added. The product was filtered and recrystallized from 90% aqueous ethanol. It was reported that majority of the compounds exhibited anticonvulsant activity.