One‐Pot Synthesis of 5 H ‐Indazolo‐[3,2‐ B ]benzo[ d ]‐1,3‐Oxazine: Two Efficient Preparative Methods

Abstract

2‐Nitrobenzaldehyde 2‐Aminobenzyl alcohol 2‐Picoline borane 5 H‐ Indazolo‐[3,2b]benzo[d]‐1,3‐oxazine 2‐Nitrobenzyl bromide Diisopropylethyl amine

The Davis–Beirut Reaction: N1,N2-Disubstituted-1H-Indazolones via 1,6-Electrophilic Addition to 3-Alkoxy-2H-Indazoles

“…Of the two isomers, 2 H -indazoles are less explored than 1 H -indazoles. 2 In previous reports, 3 our laboratory has demonstrated the utility of the Davis-Beirut reaction – an effective N,N -bond forming heterocyclization reaction – to deliver 3-alkoxy- 2H -indazoles, benzoxazin[3,2-b]-indazole, oxazolino[3,2-b]indazole, and a variety of other indazolo-fused hetero-cycles from 2-nitrobenzaldehyde or 1-(bromomethyl)-2-nitrobenzene.…”

Facile Syntheses of Novel Benzo- 1,3-dioxolo-, Benzothiazolo-, Pyrido-, and Quinolino-fused 5H-Benzo[d]-pyrazolo[5,1-b][1,3]-oxazines and 1H-Pyrazoles

“…12 It was also found that 5 H -indazolo[3,2- b ]benzo[ d ][1,3]-oxazines can be obtained in a one-pot reaction starting with o -nitrobenzaldehyde. 12e We envisaged that these methods (Scheme 1a/b) could be extended to the synthesis of a variety of novel heterocyclic analogs by, for example, introduction of a nitrogen atom in the benzo ring of 2 H -indazoles or in any of the rings fused to this benzo ring (Scheme 1c).…”

“…12 It was also found that 5 H -indazolo[3,2- b ]benzo[ d ][1,3]-oxazines can be obtained in a one-pot reaction starting with o -nitrobenzaldehyde. 12e We envisaged that these methods (Scheme 1a/b) could be extended to the synthesis of a variety of novel heterocyclic analogs by, for example, introduction of a nitrogen atom in the benzo ring of 2 H -indazoles or in any of the rings fused to this benzo ring (Scheme 1c). Indeed, a host of unique heterocycles can be envisioned in which the pyrazole ring is the common denominator and we report here that a number of benzo-1,3-dioxolo-, benzothiazolo-, pyrido-, quinolino-fused 5 H -benzo[ d ]-pyrazolo[5,1- b ]-[1,3]-oxazines and 1 H -pyrazoles are accessible in moderate to high yields (35-88%) via this N,N -bond forming heterocyclization reaction.…”

“…Rather, the major product of this reaction proved to be 2-fluoro- N -((2-nitrothiophen-3-yl)methylene)aniline ( 17 ). 18 We speculate that nitroso imine 16 is the initial product of this reaction, 12a,b but subsequent nitroso → nitro air oxidation 19 out-competes N,N -bond formation to deliver 17 rather than the targeted heterocycle 15 . This difficulty in formation of thieno-fused 1 H -pyrazole 15 appears to derive from the weak acidity of the sp 3 hybridized proton of 16’ , which thus impedes 1,4-elimination of water.…”

“…These novel heterocycles have been submitted to the NIH Molecular Libraries Small Molecule Repository (MLSMR) for high-throughput biological screening. In view of the utility of this N,N -bond forming heterocyclization, which has been demonstrated in the synthesis of a wide variety of often complex heterocycles in this work as well as in six earlier pulications, 12,14 we propose to call this method the “Davis-Beirut” reaction in recognition of the merits of international collaboration.…”