Pd2(dba)3-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4] thiadiazole with substituted anilines at conventional heating in Schlenk tube

ABSTRACT

An efficient Pd₂(dba)₃-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4]thiadiazole using conventional heating is reported. The C5-bromoimidazo[2,1-b][1,3,4]thiadiazole was synthesized using a multistep approach which started by cyclization of thiosemicarbazide with a carboxylic acid to give 2-amino[1,3,4]thiadiazoles which were further treated with 2-haloketones to give imidazo[2,1-b][1,3,4]thiadiazoles. Then, the bromination of imidazothiadiazole was done using N-bromosuccinimide to give the C5-bromo-imidazo[2,1-b][1,3,4]thiadiazole. Afterward, various C-N bond-forming approaches were attempted such as S_NAr, Cu(I), Cu(II), Pd(OAc)_2, Pd₂(dba)₃ catalyst with different ligand, additive, base, solvent and temperature conditions. Out of various approaches used, only Buchwald Hartwig amination, performed with conventional heating, gave N-arylamine-5-imidazothiadiazoles. Then, 10 different anilines with different electron-withdrawing and donating groups at different positions were employed to examine the scope and limitations of the method. Salient features of this method include conventional heating in a Schlenk tube as the reaction condition, the absence of the use of toxic isocyanides, the wide nature of substituent tolerance with anilines, and moderately good product yields.