Superior reactivity of thiosemicarbazides in the synthesis of 2-amino-1,3,4-oxadiazoles.
A facile and general protocol for the preparation of 2-amino-1,3,4-oxadiazoles is reported. This method relies on a tosyl chloride/pyridine-mediated cyclization of a thiosemicarbazide, which is readily prepared by acylation of a given hydrazide with the appropriate isothiocyanate. Cyclization of the thiosemicarbazide consistently outperforms the analogous semicarbazide cyclization under these conditions, for 18 distinct examples. Utilizing this protocol, we have prepared 5-alkyl- and 5-aryl-2-amino-1,3,4-oxadiazoles in 78-99% yield.
Dolman
Sarah J
SJ
Department of Process Research, Merck Frosst Centre for Therapeutic Research, 16711 Route Transcanadienne, Kirkland, Québec, Canada H9H 3L1. sarah_dolman@merck.com
Gosselin
Francis
F
O'Shea
Paul D
PD
Davies
Ian W
IW
D010080:Oxazoles / Q000138:chemical synthesis*; D012663:Semicarbazides / Q000737:chemistry*
D010080:Oxazoles; D012663:Semicarbazides