Microwave-Assisted Copper(II)-Catalyzed Cascade Cyclization of 2-Propargylamino/Oxy-Arylaldehydes andO-Phenylenediamines: Access to Densely Functionalized Benzo[f]Imidazo[1,2-d][1,4]Oxazepines and Benzo[f]Imidazo[1,2-d][1,4]Diazepines

Abstract

A highly efficient microwave-assisted copper(II)-catalyzed cyclization cascade was established starting from readily accessible O/N-propargylated 2-hydroxy or 2-aminobenzaldehydes and o-phenylenediamines to synthesize densely functionalized imidazo [1,2-d][1,4]oxazepines and imidazo [1,2-d][1,4]diazepines in high yields (up to 93%). This one-pot two-step process was found to be highly atom economical (−H 2 O, −H 2 ) and operationally simple and enabled the generation of two new heterocycle rings (seven-and five-membered) and three new C−N bonds in a single synthetic operation. These reactions well tolerated a variety of substituents including electron-donating and electron-withdrawing groups and furnished the desired fused heterocycles in high yields under microwave irradiation in a very short reaction time. The mechanism of the established protocol involves sequential imine formation−intramolecular cyclization−air oxidation followed by 7-exo-dig cyclization steps. A comparative study between the microwave-assisted approach and conventional heating was also performed to demonstrate the advantages of the microwave-assisted protocol in terms of high yield and shorter reaction time.

Synthetic aspects of 1,4- and 1,5-benzodiazepines usingo-phenylenediamine: a study of past quinquennial

“…Rajput and co-workers 103 reported a novel microwave-assisted process to synthesize 1,4-BZDs derivatives ( 49 ) using OPD ( 1 ) and N-propargylated-2-aminobenzaldehyde ( 22 ) with a copper( ii ) catalyst (10 mol%), K 2 CO 3 (3 equiv.) and a DMF solvent.…”

Copper Catalyzed Synthesis of Heterocyclic Molecules via C–N and C–O Bond Formation under Microwaves: A Mini-Review

“…The corresponding oxazepane/diazepines derivatives 60/61 were synthesized by a cascade reaction of various O/N-propargylated 2-hydroxybenzaldehydes 55/56 and o-phenylenediamines 57 in the presence of 10 mol % of Cu­(OTf) 2 and K 2 CO 3 as base in DMF under microwave irradiation at 100 °C for 15 min (Scheme ). Both electron withdrawing and electron donating groups showed good to excellent yield …”

“…Both electron withdrawing and electron donating groups showed good to excellent yield. 22 The intermediate imine A produced from the reaction between aldehyde 55/56 and o-phenylenediamine 57 underwent Cu(II) catalyzed intramolecular 5-endo-trig cyclization, followed by aerial oxidation/aromatization, to provide the imidazole intermediate 58/59 through species B. The internal alkyne of 58/59 is activated by the copper(II) catalyst in the presence of a base, resulting in the production of desired products 60/61 followed by 7-exo-dig cyclization (Figure 10).…”

Microwave-assisted one-pot two-step imine formation–hetero-Diels–Alder–detosylation/aromatization sequence: direct access to dibenzo[b,h][1,6]naphthyridines

“…N-(4-Chloro-2-formylphenyl)-N-(3-(4-methoxyphenyl)prop-2yn-1-yl)-4-methylbenzenesulfonamide (1f ). 22 Purification by flash column chromatography on silica gel and eluting with a petroleum ether-ethyl acetate mixture (90 : 10 to 85 : 15, v/v) afforded the title compound as a white solid; mp: 103-105 °C; yield: 5.07 g, 91%.…”