120 1,2-Azoles and 1,3-Azoles
Regiocontrol can also be achieved by using a 1,3-dicarbonyl equivalent, for example an alkynyl-ketone – the terminal
alkyne carbon is at the oxidation level of a carbonyl group. In a nice example of this, 5-(isoxazol-5-yl)pyrazoles can be
constructed, as shown.
Isoxazoles are similarly effi ciently produced from 1,3-dicarbonyl compounds or synthetic equivalents thereof, using
hydroxylamine.
There are of course many ways to produce 1,3-dicarbonyl compounds; a neat and effi cient route when one of the car-
bonyl groups is to be an aldehyde utilises an enamine as aldehyde equivalent, obtained by a condensation reaction of
dimethylformamide dimethyl acetal (DMFDMA) to a ketone.
Synthesis of isoxazoles and pyrazoles from alkynes
(1,5- and 3, 4-bonds made)
This method is of most relevance to the synthesis of isoxazoles, though pyrazoles can also be produced. Nitrile oxides
(R-CKN-O) readily take part in 1,3-dipolar cycloadditions with alkenes or alkynes generating fi ve-membered
heterocycles. Addition to alkynes produces isoxazoles, directly. Addition to alkenes gives 4,5-dihydroisoxazoles (iso-
xazolines), but these can be easily dehydrogenated. Though less frequently used, a nitrile imine will add to an alkyne
producing a pyrazole.
Nitrile oxides are usually generated in situ, in the presence of the other reactant, either by dehydration of a nitro com-
pound (RCH 2 NO 2 ) using phenyl isocyanate or by base-catalysed elimination of hydrogen halide from a halo-oxime
(RC(Hal)=NOH), as illustrated. Nitrile imines can be similarly accessed by dehydrohalogenation of hydrazonoyl
halides themselves prepared by NBS or NCS treatment of the corresponding hydrazones.