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Issue 4, 2017
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A convergent synthesis of 1,3,4-oxadiazoles from acyl hydrazides under semiaqueous conditions

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Abstract

The 1,3,4-oxadiazole is an aromatic heterocycle valued for its low-lipophilicity in drug development. Substituents at the 2- and/or 5-positions can modulate the heterocycle's electronic and hydrogen bond-accepting capability, while exploiting its use as a carbonyl bioisostere. A new approach to 1,3,4-oxadiazoles is described wherein α-bromo nitroalkanes are coupled to acyl hydrazides to deliver the 2,5-disubstituted oxadiazole directly, avoiding a 1,2-diacyl hydrazide intermediate. Access to new building blocks of oxadiazole-substituted secondary amines is improved by leveraging chiral α-bromo nitroalkane or amino acid hydrazide substrates. The non-dehydrative conditions for oxadiazole synthesis are particularly notable, in contrast to alternatives reliant on highly oxophilic reagents to effect cyclization of unsymmetrical 1,2-diacyl hydrazides. The mild conditions are punctuated by the straightforward removal of co-products by a standard aqueous wash.

Graphical abstract: A convergent synthesis of 1,3,4-oxadiazoles from acyl hydrazides under semiaqueous conditions

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Article information


Submitted
13 Jan 2017
Accepted
16 Feb 2017
First published
23 Feb 2017

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2017,8, 3187-3191
Article type
Edge Article

A convergent synthesis of 1,3,4-oxadiazoles from acyl hydrazides under semiaqueous conditions

K. Tokumaru and J. N. Johnston, Chem. Sci., 2017, 8, 3187 DOI: 10.1039/C7SC00195A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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