Oxy-and Amino-1,2-azoles

Amino-1,3-azoles exist as the amino tautomers, though 2-aryIsulfonylaminoth-iazoles have been shown to exist as the imino tautomers. 2-Amino-1,3-azoles tend to be more stable than other isomers. All amino-1,3-azoles protonate on the ring nitrogen. 2-Aminothiazole has a pA of 5.39 which compares with the 

The amino-1,3-azoles behave as normal arylamines, for example undergoing carbonyl condensation reactions, easy electrophilic substitutions, and diazoti-sation, though 2-aminooxazoles cannot be diazotised, presumably due to the greater electron-withdrawal by the oxygen. In appropriate cases, good yields of diazoazoles, as opposed to azole-diazoniums salts, can be obtained from aminoimidazoles.  

The oxygen-substituted 1,3-azoles exist in their carbonyl tautomeric forms. That there is little aromatic character left in such systems is nicely illustrated by the acid-catalysed dimerisation of imidazol-2-one, which acts as an enamide in the process.  

The bromination of thiazol-2-one, at C-5, is also a nice demonstration of relative reactivity here the double bond carries both sulfur and nitrogen, and it is the latter, i.e. the enamide rather than the thioenol ester character, which dictates the site of electrophilic attack.  

Alkylation of the 1,3-azolones can take place either on the oxygen, giving alkyloxyazoles, or on nitrogen for example, thiazol-2-one reacts with diazomethane giving 2-methoxythiazole, but with methyl iodide/methoxide, to give 3-methylthiazol-2-one.  

Pyrazolones also condense with aldehydes in aldol-type processes, or react with other electrophiles such as carbon disulfide, in each case reaction presumably proceeding via the enol tautomer, or its anion. In basic solution oxazol-3-ones alkylate either on oxygen or nitrogen and the choice of base can influence the ratio.  

An intriguing and simple synthesis of a useful bromo-allene depends on the lead(IV) acetate oxidation of a bromopyrazolone, as shown.  

Amino-1,2-azoles exist as the amino tautomers. Aminopyrazoles and amino-isothiazoles are relatively well behaved aromatic amines, for example 3(5)-aminopyrazole undergoes substituent-AT-acetylation and easy electrophilic bromina-tion at C-4. Diazotisation and a subsequent Sandmeyer reaction provides routes to halo-isothiazoles, and azidopyrazoles.  

Diazotisation of 4-aminopyrazoles, then deprotonation yields stable diazopyr-azoles.  

There are parallels, but also methods unique to particular 1,2-azoles, in the principal methods available for the construction of pyrazoles, isothiazoles and isoxazoles neither the reaction of propene with sulfur dioxide and ammonia at 350 °C which gives isothiazole itself in 65% yield, nor a synthesis from propargyl aldehyde and thiosulfate (shown below) have direct counterparts for the other 1,2-azoles. 

Diazotisation of 4-amino-pyrazoles, then deprotonation yields isolable diazo-pyrazoles.  

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