Iodine‐Catalyzed Synthesis of Spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones under Mild Conditions

Abstract

The I2‐catalyzed preparation of spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones from 2‐aminobenzohydrazide and isatins in MeCN at room temperature in good‐to‐excellent yields is described. The structure of 3 was corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS data). A plausible mechanism for this type of reaction is proposed (Scheme 2).

Advances in the Synthesis of Benzo‐Fused Spiro Nitrogen Heterocycles: New Approaches and Modification of Old Strategies

“…The largest amount of studies on the synthesis of spiro‐fused heterocycles is carried out using indole compounds, including 2,3‐dioxo derivatives, as one of the starting reaction components. Researchers’ attention to the development of new approaches both to the preparation of isatin themselves, [95,96] and their use in numerous synthesis schemes for various heterocyclic systems is due to the presence of several reactive centers in the structure of 1 H ‐pyrrole‐2,3‐dione. A comprehensive review of spiro‐fused heterocycles synthesis using isatin was published in 2012 [35] .…”

Design, Synthesis, and Biological Assessment of Biased Allosteric Modulation of the Urotensin II Receptor Using Achiral 1,3,4-Benzotriazepin-2-one Turn Mimics

“…Although their achiral aza-counterparts may be inherently less costly to produce, benzotriazepines have been less frequently employed in medicinal chemistry programs. − For example, benzotriazepin-2-one 1 was employed in the development of achiral orally active cholecystokinin-2 (CCK 2 ) antagonists, , and 5-cyclohexyl benzotriazepin-2-one derivative 2 exhibited activity as a parathyroid hormone-1 receptor antagonist (Figure ). Benzotriazepin-2-ones have also been claimed to possess psychostimulant, antidepressant, anorexigenic, and antihypertensive activities . Benzotriazepin-2-ones thus merit further investigation as scaffolds for generating ligands to biologically relevant receptors.…”

Chemoselective Alkylation for Diversity-Oriented Synthesis of 1,3,4-Benzotriazepin-2-ones and Pyrrolo[1,2][1,3,4]benzotriazepin-6-ones, Potential Turn Surrogates

“…For example, 5-cyclohexyl triazepinones 3 and 4 have, respectively, exhibited activity as a parathyroid hormone-1 receptor antagonist and an orally active cholecystokinin-2 (CCK 2 ) antagonist (Figure ). 1,3,4-Benzotriazepin-2-ones have also been claimed to possess psychostimulant, antidepressant, anorexigenic, and antihypertensive properties . Although relatively little is known about 1,3,4-triazepin-2-one conformation, similar to the amino acid component in 1,4-diazepin-2-ones, the aza-phenylglycine residue of 7-chloro-3,5-diphenyl-1,2-dihydro-3 H -1,3,4-benzotriazepin-2-one 5 was observed by X-ray crystallography to adopt ϕ- and ψ-dihedral angle values close to those of the central residue of an ideal γ-turn …”

“…Since original syntheses from 2-aminobenzophenone, 1,3,4-benzotriazepin-2-ones have been commonly prepared by cyclization of the corresponding hydrazone with a phosgene equivalent and by a one-pot annulation with a carbazate often at high temperature (e.g., 190 °C). Ring closure has also been achieved by palladium-catalyzed cyclization of aryl isocyanates and 2-haloaryl hydrazones under microwave irradiation as well as condensation of anthranilic acid hydrazide with isatins, which provided the corresponding spiro­[1,3,4-benzotriazepine-2,3′-indole]-2′,5­(1 H ,1′ H )-diones . Benzotriazepinone skeletons have been alkylated on ring nitrogen and arylated at C5 using copper catalysis in solution and on microelectrode arrays; however, nitrogen protection has been essential for chemoselectivity.…”