Regioselective Synthesis of 2-Amino-Substituted 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Derivatives via Reagent-Based Cyclization of Thiosemicarbazide Intermediate

다국어 초록 (Multilingual Abstract)

<P>A regioselective, reagent-based method for the cyclization reaction of 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole core skeletons is described. The thiosemicarbazide intermediate <B>3</B> was reacted with EDC·HCl in DMSO or <I>p</I>-TsCl, triethylamine in <I>N</I>-methyl-2-pyrrolidone to give the corresponding 2-amino-1,3,4-oxadiazoles <B>4</B> and 2-amino-1,3,4-thiadiazoles <B>5</B> through regioselcective cyclization processes. The regioselectivity was affected by both R<SUP>1</SUP> and R<SUP>2</SUP> in <I>p</I>-TsCl mediated cyclization. It is shown in select sets of thiosemicarbazide <B>3</B> with R<SUP>1</SUP>(benzyl) and R<SUP>2</SUP>(phenyl). 2-Amino-1,3,4-oxadiazole <B>4</B> was also shown in the reaction of <I>p</I>-TsCl mediated cyclization. The resulting 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole core skeleton are functionalized with various electrophiles such as alkyl halide, acid halides, and sulfornyl chloride in high yields.</P><P><B>Graphic Abstract</B>
<IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/joceah/2013/joceah.2013.78.issue-2/jo302324r/production/images/medium/jo-2012-02324r_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jo302324r'>ACS Electronic Supporting Info</A></P>