Synthesis of Substituted 2,3-Benzodiazepines

Abstract

A new, four-step synthetic route for substituted 2,3-benzodiazepines 1, starting from aldehyde 4, was developed with excellent overall yields. This route included the 1,2-addition of various aromatic Grignard reagents to 4, PCC oxidation, and aerobic Wacker-type oxidation of the olefinic group of 6, followed by condensation of the resulting 1,5-dicarbonyl 7 with NH. Isoquinolones 9 were obtained when an aldehyde group was used instead of a ketone. The key structures were confirmed by X-ray single-crystal diffraction analysis.

Weakly Coordinating, Ketone-Directed Cp*Co(III)-Catalyzed C–H Allylation on Arenes and Indoles

“…ortho -Allyl aromatic ketones are very useful synthons for many biologically active natural products, and they are also used as important intermediates for different structural conversions . They can also serve as key building blocks to access several π-extensions directly .…”

Palladium-Catalyzed Benzodiazepines Synthesis

“…2,3-Benzodiazepines 2,3-benzodiazepines are known for being tranquilizing agents and acting as non-competitive AMPA antagonists and their structure is found in biologically active compounds, such as girisopam and nerisopam, too. For this reason, an efficient method has been developed for their synthesis starting from 2-allyl benzo-ketones 94, exploiting an aerobic Wacker oxidation on terminal olefin, and the subsequent reaction of hydrazine on the present and formed keto group (Scheme 46) [103]. The classic PdCl 2 /CuCl 2 system in combination with molecular oxygen was better than any other conditions tested.…”

Construction of Nitrated Benzo[3.3.1]bicyclic Acetal/Ketal Core via Nitration of o-Carbonyl Allylbenzenes

“…The required starting materials for 2 were easily prepared from substituted benzaldehydes 3 in moderate overall yields according to reported procedures . To examine the nitration of o -carbonyl allylbenzenes, we employed 2a (prepared from 3-hydroxylbenzaldehyde ( 3a ) via a three-step protocol of O-allylation, Claisen rearrangement, O-methylation) as the model substrate to screen the + NO 2 -mediated reaction conditions. On the basis of the considered synthetic operation and use of cheaper reagent, the common combination of fuming HNO 3 (97%, 0.5 mL) and H 2 SO 4 (98%, 2 mL) was first examined under open vessel conditions (Table ).…”

“…The expeditious one-step transition-metal-free route sets up a novel framework having the linkage of 4 or 5 newly formed bonds, including 2 or 3 C–N bonds and 2 C–O bonds under open vessel conditions. The required starting materials for 2 were easily prepared from substituted benzaldehydes 3 in moderate overall yields according to reported procedures . To examine the nitration of o -carbonyl allylbenzenes, we employed 2a (prepared from 3-hydroxylbenzaldehyde ( 3a ) via a three-step protocol of O-allylation, Claisen rearrangement, O-methylation) as the model substrate to screen the + NO 2 -mediated reaction conditions.…”