Reactivity and substituent effects in the cyclization of N -aryl-2-nitrosoanilines to phenazines

A Modular Synthetic Route Involving N-Aryl-2-nitrosoaniline Intermediates Leads to a New Series of 3-Substituted Halogenated Phenazine Antibacterial Agents

“…General Two-Step Procedure for the Synthesis of 3-Chloro-1-methoxyphenazines (38, 50−58). 44,45 Step 1. 4-Bromoaniline (303 mg, 1.76 mmol) dissolved in 2 mL of N,N-dimethylformamide was added dropwise to a stirring solution of potassium tert-butoxide (416 mg, 4.80 mmol) in N,N-dimethylformamide (12 mL) at −60 °C.…”

“…We came across an interesting method reported by Wróbel and co-workers utilizing aniline starting materials to access N -aryl-2-nitrosoaniline intermediates ( e.g. , 14 , Scheme ) which were then cyclized to phenazines upon treatment with the silylating agent N , O -bis­(trimethylsilyl)­acetamide (BSA) in N , N -dimethylformamide. , In Wróbel’s approach, 3-chloro-1-methoxyphenazines ( 15 , R = H) were accessed and we envisioned this as an entry point to investigate novel 3-subsituted HPs ( e.g. , 16 ).…”

Design, synthesis and evaluation of halogenated phenazine antibacterial prodrugs targeting nitroreductase enzymes for activation

“…Our synthesis of phenazine 7 was inspired by Wróbel and coworkers. [25][26][27][28] 1-Methoxyphenazine 7 was then subjected to (1) demethylation with boron tribromide (BBr 3 , 95% yield), and (2) bromination using N-bromosuccinimide (NBS) to synthesize 6,8-CF 3 -HP (98% yield). We found this route to be scalable, producing 326 milligrams of 6,8-CF 3 -HP from 1 gram of starting 3,5-bis(trifluoromethyl)aniline 5.…”

Sodium sulfide-promoted regiodefined redox condensation of o-nitroanilines with aryl ketones to benzo[a]phenazines and quinoxalines

“…On the basis of these results as well as the regiospecificity of the formation of quinoxaline cores when substituted o -nitroanilines were used as the oxidizing partner, we proposed a plausible reaction mechanism that starts with a partial reduction of o -nitroaniline 1a into highly reactive o -nitrosoaniline A , 11 which then reacts with the active methylene group of α-tetralone 2a to provide imine B . Such a reaction could be catalyzed by a base, which was Na 2 S·3H 2 O in the present case.…”