Introduction
The 1,3-dipolar cycloaddition is a classic and widely used reaction in modern synthetic organic and pharmaceutical chemistry that consists of the reaction of a dipolarophile with a 1,3-dipole yielding various five-membered heterocycles (by our examined reagents: oxazoles, diazoles, thiazoles, oxadiazoles, thiadiazoles and their iso or saturated variants).[
1
] These heterocycles are versatile synthetic intermediates, playing a significant role in the synthesis of many biologically active natural products,[
2
] alkaloids,[
3
] chemically modified oligonucleotides,[
4
] peptides[
5
] and other pharmacologically active compounds[
6
] or prevailing drugs.[
7
]
Preparation
All 1,3-dipoles are relatively unstable linear molecules that can be generated in situ (Scheme [1 ]).[
1a
] A simple way to form nitrile imines is the dehydrohalogenation of hydracidic halides using a base, mostly triethylamine.[1b ]
[2a ] Nitrile oxides may be generated from nitro compounds or from the halogenation of aldoximes followed by a dehydrohalogenation caused by an adequate base. In the reactions of nitrile oxides high syn -selectivity can be observed.[
1a,7
] The formation of in situ nitrile sulfides is attained by the thermal or microwave-assisted thermolysis and also photolysis of various heterocyclic compounds containing a C=N–S bond.[
8
]
Scheme 1 Simple ways to the in situ generation of dipoles
