116 1,2-Azoles and 1,3-Azoles
If the nitrogen of the starting amide also carries an alkyl group, cyclisation can only lead to an overall neutral prod-
uct by adopting a zwitterionic structure, for which no neutral resonance form can be written – a mesoionic structure.
Mesoionic oxazolones (named ‘münchnones’ after their discovery at the University of München, Germany; strictly
called 1,3-oxazolium-5-olates) undergo ready dipolar cycloadditions, with loss of carbon dioxide from the initial adduct.
Amino-azoles exist as the amino tautomers and all protonate on the ring nitrogen. The pKaH of 2-aminoimidazole, at
8.46 the most basic isomer, refl ects the symmetry of the resonating guanidinium system within its cation.
The amino-azoles behave as typical arylamines, for example they can be diazotised, thus providing routes to halo-azoles.
1,3-Azoles ring synthesis – disconnections
There are three important disconnections for the construction of 1,3-azoles, summarised below with the new bonds
made in the processes shown.
Synthesis of thiazoles and imidazoles from -halo-ketones
(1,5- and 3,4-bonds made)
This disconnection is most important for the synthesis of thiazoles. A thioamide is reacted with an -halo-ketone, with the
fi rst bond made being between sulfur and carbon – the 1,5-bond. Shown below are the syntheses of 2,4-dimethylthiazole
where the heteroatoms are provided by thioacetamide, and of 2-aminothiazole, in which 1,2-dichloroethyl ethyl ether