N–N Bond Formation between Primary Amines and Nitrosos: Direct Synthesis of 2-Substituted Indazolones with Mechanistic Insights

Abstract

A concise, one-step route to indazolones from primary alkyl amines and o-nitrobenzyl alcohols is reported. The key step in this readily scalable indazolone forming process involves base-mediated in situ o-nitrobenzyl alcohol → o-nitrosobenzaldehyde conversion. Although this functional group interconversion is known to be useful for 2 H-indazole synthesis, its reactivity was modulated for indazolone formation.

Photochemical Preparation of 1,2-Dihydro-3H-indazol-3-ones in Aqueous Solvent at Room Temperature

“…15 As a result, reaction of (5-chloro-2-nitrophenyl)methanol with n -butylamine gave indazolone 14 in only 10% yield with indazolone 1 as a side product in 9% yield (note: three side-products having m/z < 100 were found by LCMS with each accounting for <10% of the recovered mass). Under strongly alkaline conditions, 9 (3-methyl-2-nitrophenyl)methanol provided the corresponding indazolone 15 in marginal yields after 48 h of reaction time, presumably due to issues related to benzylic proton acidity affecting aci -nitronate anion formation. In contrast, this problem was eliminated under the reaction conditions reported here and 15 was obtained in 69% yield.…”

“…Another challenging class of substrates for base-mediated indazolone formation 9 is reactions of benzylic amines, due to side reactions associated with the benzylic hydrogen’s acidity. Here, in the absence of base, benzylamine gave 21 in 69% yield.…”

Accessing Multiple Classes of 2H-Indazoles: Mechanistic Implications for the Cadogan and Davis–Beirut Reactions

“…Much of the trifluoromethylcontaining N-oxide 22 was deoxygenated even at room temperature. Using benzylamine as the starting material did not deliver 23 under basic conditions due to side-reactions leading to 3-phenylquinazoline formation, 13 but when KOH was excluded and the reaction was carried out under photochemical conditions, 31 23 was obtained in 29% yield. Unfortunately, use of an aryl rather than alkyl amine is incompatible with these reaction conditions; for example, N-aryl 2H-indazole N-oxide 24 was not produced under either basic or photochemical conditions.…”

Photocatalyst‐free Synthesis of Indazolones under CO2 Atmosphere

“…Although, liquid CO 2 has been employed as a unique solvent for organic compounds and applied to synthetic reactions, use of CO 2 as a mediator for organic reactions is rare . The overall transformation of the present reaction includes C−N bond and N−N bond constructions via C(sp3)−H and N−H bonds cleavage by UV light irradiation under CO 2 atmosphere (1.0 atm, flow), to furnish indazolones in up to 96 % yield in only one step without any photocatalyst, acid, or base. The reaction pathway is discussed based on control experiments.…”