Synthesis of Bis‐Heterocyclic 1<i>H</i>‐Imidazole 3‐Oxides from 3‐Oxido‐1<i>H</i>‐imidazole‐4‐carbohydrazides

Abstract

Abstract The reaction of 1 H ‐imidazole‐4‐carbohydrazides 1 , which are conveniently accessible by treatment of the corresponding esters with NH 2 NH 2 ⋅H 2 O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (=hydrazinecarbothioamides) 4 in high yields ( Scheme 2 ). Whereas 4 in boiling aqueous NaOH yielded 2,4‐dihydro‐3 H ‐1,2,4‐triazole‐3‐thiones 5 , the reaction in concentrated H 2 SO 4 at room temperature gave 1,3,4‐thiadiazol‐2‐amines 6 . Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7 , which, under basic conditions, undergo cyclization to give 2,4‐dihydro‐3 H ‐1,2,4‐triazol‐3‐ones 8 ( Scheme 3 ). Treatment of 1 with Ac 2 O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol‐2‐ones was not observed ( Scheme 4 ). It is important to note that, in all these transformations, the imidazole N ‐oxide residue is retained. Furthermore, it was shown that imidazole N ‐oxides bearing a 1,2,4‐triazole‐3‐thione or 1,3,4‐thiadiazol‐2‐amine moiety undergo the S‐transfer reaction to give bis‐heterocyclic 1 H ‐imidazole‐2‐thiones 11 by treatment with 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione ( Scheme 5 ).