Formation of Synthetically Versatile 2-Aminobenzophenones from Readily Accessed Acyl Hydrazides

Abstract

Herein, we report the transformation of readily accessed acyl hydrazides into protected 2-aminobenzophenones via a two-step process involving an aryne-based molecular rearrangement followed by a one-pot addition–elimination procedure. The assembly of the scaffold is tolerant of a wide variety of functional groups, and the carbamate group on the product can be facilely removed to afford highly valuable 2-aminobenzophenones. Application of the protocol was demonstrated in the synthesis of neurological medicine phenazepam.

o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors

“…Moreover, acridones were obtained from o -halobenzaldehyde hydrazones, the formation of which included an additional intramolecular S N Ar reaction and demethylation. Recently, Chudasama and co-workers reported a preparation of 2-hydrazobenzophenones 9-195 from arynes and readily achievable acyl hydrazides 9-194 (Scheme b). , Three plausible pathways were proposed for this transformation, all of which could lead to the formation of 9-195 . The 2-hydrazobenzophenone products 9-195 could be further converted to 1 H -/2 H -indazoles and 2-aminobenzophenones …”

“…The 2-hydrazobenzophenone products 9-195 could be further converted to 1H-/2H-indazoles 707 and 2aminobenzophenones. 708 In a study carried out by Wu, Sha, and co-workers on the reaction between 2-carboxylic acid ester substituted aziridines 9-196 and arynes, they found that indole spiro-derivatives 9-197 were obtained under anhydrous conditions (Scheme 193a). 591 Mechanistically, ammonium salt 9-198 could be formed via an aryne nucleophilic annulation reaction, which is then converted to 1-benzyl-2-methyleneindolin-3-ones 9-199 through ring-opening.…”

“…658 In 2019, Chudasama et al disclosed a synthesis of neurological medicine phenazepam (14-167). 708 As shown in Scheme 328, the reaction of acyl hydrazide 14-164, generated from 2-chlorobenzaldehyde and diisopropyl azodicarboxylate (DIAD), with benzyne produced 2-hydrazobenzophenone 14-165 in 67% yield through a benzyne-based molecular transformation process. Compound 14-166 was then obtained from 14-165.…”

Visible‐Light‐Mediated Photocatalyst‐Free Hydroacylation of Azodicarboxylic Acid Derivatives with 4‐Acyl‐1,4‐dihydropyridines

“…In the presence of tetrabutylammonium difluorotriphenylsilicate (TBAT), the adduct 4a readily reacted with Kobayashi aryne precursor to provide the insertion product 8 in 84% yield, which could be further applied to the synthesis of the analogue of neurological medicine phenazepam. [ 17 ]…”