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17.2.1.1.2.1.4 Method 4: By Oxidation of Pyrazol-1-amines

DOI: 10.1055/sos-SD-017-00353

Döpp, H.; Döpp, D.Science of Synthesis, (200417236.

The oxidation of pyrazol-1-amines is used in one of the most effective syntheses of monocyclic 1,2,3-triazines. The starting pyrazol-1-amines are prepared by N-amination of pyrazoles with hydroxylamine-O-sulfonic acid in aqueous sodium hydroxide,[‌9‌,‌261‌,‌262‌] or, after deprotonation with sodium hydride, by reaction with (O-mesitylenesulfonyl)hydroxyl­amine.[‌26‌,‌261‌,‌262‌] Unsymmetrically substituted pyrazoles 68 give a mixture of isomeric pyra­zol-1-amines 69 and 70 (Scheme 11), which in most cases can be separated.[‌33‌,‌261‌,‌262‌] However, this is not normally required as on oxidation both isomers yield the same 1,2,3-tri­azine 71.[‌9‌,‌26‌] Several different oxidants are used, including lead(IV) acetate (effective for methyl and phenyl-1,2,3-triazines, but not for the parent heterocycle),[‌9‌,‌26‌,‌42‌] lead(IV) oxide in the presence of trifluoroacetic acid,[‌26‌] nickel peroxide,[‌8‌,‌9‌,‌26‌] iodine (and iodine chloride or iodine bromide),[‌33‌] sodium periodate,[‌52‌,‌261‌] or anodic oxidation.[‌47‌] Labelling experiments with 3,5-dimethylpyrazol-1-[15N]amine show that the N-amino group forms the central nitrogen (N2) atom of the 2,6-dimethyl-1,2,3-triazine, which is formed by oxidation with lead(IV) acetate.[‌60‌] 1,2,3-Triazine (yield 18%) has been prepared by the oxidation of pyrazol-1-amine with nickel peroxide,[‌8‌] but the yield obtained (from a trace to 20%) depends upon the quality of the reagent used.[‌26‌] Oxidation with lead(IV) oxide in the presence of trifluoroacetic acid is more reliable,[‌26‌] and oxidation with iodine works well in the presence of aqueous potassium hydrogen carbonate and dichloromethane in a two-phase system.[‌48‌] However, overall sodium periodate seems to be the best oxidant for the ring transformation of pyrazol-1-amines providing good reproducibility and yields in the syntheses of 1,2,3-triazine, methylated 1,2,3-triazines,[‌52‌] and even methyl 1,2,3-triazinecarboxylates. However, the method fails with 1-aminopyrazoledicarboxylates or 4-nitropyrazol-1-amine.[‌261‌] The electrooxidation of pyrazol-1-amines is best carried out when pyridine, or water, is added to the solvent (MeCN); yields of unsubstituted, methyl-, and phenyl-substituted 1,2,3-triazines are then moderate to good.[‌47‌]

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