4.

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1,3,4-Oxadiazoles
J. HILL
University of Salford

4.23.1 INTRODUCTION
4.23.2 STRUCTURE
4.23.2.1 TheoreticalMethods
4.23.2.2 Structural Methods
4.23.2.2.1
H NMR spectroscopy
4.23.2.2.2 UV spectroscopy
4.23.2.2.3 IR and Raman spectroscopy
4.23.2.2.4 Mass spectrometry
4.23.2.2.5 Other spectroscopic methods and physical properties
4.23.2.3 Thermodynamic Aspects {Melting and Boiling Points, Solubility, Aromaticity and
Conformation)
4.23.2.4 Tautomerism
4.23.3 REACTIVITY
4.23.3.1 Introduction
4.23.3.2 Fully Conjugated Rings; Reactivity at Ring Atoms
4.23.3.2.1 Thermal and photochemical reactions, formally involving no other species
4.23.3.2.2 Electrophilic attack at nitrogen
4.23.3.2.3 Electrophilic substitution at carbon
4.23.3.2.4 Reaction of nucleophiles at carbon
4.23.3.2.5 Nucleophilic attack at hydrogen; acidity
4.23.3.2.6 Photoreactions and cycloadditions
4.23.3.2.7 Reaction with metals
4.23.3.3 Non-aromatic Compounds
4.23.3.3.1 2,3-Dihydro-l,3,4-oxadiazoles (A2-l,3,4-oxadiazolines)
4.23.3.3.2 2,5-Dihydro-l,3,4-oxadiazoles (A3-l,3,4-oxadiazolines)
4.23.3.3.3 2,3,4,5-Tetrahydro-l,3,4-oxadiazoles (1,3,4-oxadiazolidines)
4.23.3.4 Reactivity of Substituents
4.23.3.4.1 C-Linked substituents
4.23.3.4.2 N-Linked substituents
4.23.3.4.3 O- and S-Linked substituents
4.23.4 SYNTHESIS
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4.23.4.1 Ring Synthesis
4.23.4.1.1 Cyclization with the formation of one bond
4.23.4.1.2 Cyclization with the formation of two bonds
4.23.4.1.3 Cyclization with the formation of three bonds
4.23.4.2 Ring Transformations
4.23.5 APPLICATIONS
4.23.5.1 Biologically Active 1,3,4-Oxadiazoles
4.23.5.2 Other Applications

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4.23.1 INTRODUCTION
1,3,4-Oxadiazole (1) is a thermally stable neutral aromatic molecule (65JA5800). Other
aromatic systems are 1,3,4-oxadiazolium cations (2) and the exocyclic-conjugated mesoionic
1,3,4-oxadiazoles (3) and 1,3,4-oxadiazolines (4). Also known are derivatives of the
non-aromatic reduced systems, 2,3-dihydro-l,3,4-oxadiazole (A2-1,3,4-oxadiazoline; 5),
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