1,2-Azoles and 1,3-Azoles 117is utilised in lieu of chloroethanal and the heteroatoms derive from thiourea; these are typical examples of the Hantzsch
synthesis (note there is an important pyridine ring synthesis also named a Hantzsch synthesis – page 45).
This route can also be utilised to prepare imidazoles, for example using amidines (RC(=NH)NH 2 ) gives 2-substituted
(alkyl or aryl) imidazoles and using N-acetylguanidine produces 2-acetylamino-imidazoles.
Synthesis of 1,3-azoles from 1,4-dicarbonyl compounds
(1,2- and 1,5-bonds made)
This route is of most importance for the synthesis of oxazoles, but thiazoles and imidazoles can also be accessed via this
strategy. The amides of -amino-ketones produce oxazoles when exposed to acidic dehydrating conditions – note the
analogy to the ring closure of 1,4-diketones to give furans (page 105).
The synthesis of the 5-amino-oxazole shown below illustrates the general principal that if a nitrile is utilised instead of
a ketone/aldehyde, the result is an amino-heterocycle: the ring closure substrate is prepared in this case from aminoma-
lononitrile by a dicyclohexylcarbodiimide (DCC) mediated amide bond formation with a carboxylic acid.
The introduction of ammonia to an -acylthio-ketone will generate a thiazole, and similarly ammonia with an
-acylamino-ketone will produce an imidazole, as shown.