1,2-Azoles and 1,3-Azoles 1191,2-Azoles ring synthesis – disconnections
There are two important disconnections for the construction of 1,2-azoles, summarised below with the new bonds
made in the processes shown.
Synthesis of pyrazoles and isoxazoles from 1,3-dicarbonyl compounds
(1,5- and 2,3-bonds made)
This is the most obvious route to the 1,2-azoles and is of major relevance for the synthesis of pyrazoles and isoxazoles.
Condensation of a 1,3-diketone, or synthetic equivalent, with a hydrazine or with hydroxylamine (each is doubly
nucleophilic) initially intermolecularly and then intramolecularly using the second heteroatom, produces the aromatic
1,2-azole directly. Substituted hydrazines generally give mixtures of regioisomers, unless a 1,3-dicarbonyl component
(or an equivalent) having markedly different reactivities at the two carbonyl groups is used. For example phenylhydra-
zine reacts with ethyl acetoacetate to produce only one pyrazolone (note also that the higher oxidation level of one of
the carbonyl groups is refl ected in the oxidation level of that carbon in the product).