Structural Characterization of a Phenoxazine Analog Formed as a By‐product of the Synthesis of a 3‐Amino‐N,N‐dimethylsalicylamide

Structural Characterization of a Benzoxazinophenoxazine Formed as a By‐Product During the Synthesis of a 3‐Amino‐N,N‐dimethylsalicylamide

“…The upfield shift of the carbon to which the aromatic singlet was bound is consistent with a carbon that has multiple electron‐donating substituents, ( e.g., oxygen or nitrogen) located β to the carbon. The chemical shift of this 1 H/ 13 C resonant pair is quite similar to that of the 1‐position (6.53/99.9 ppm) of the previously characterized 4,6‐bis‐( N,N ‐dimethylcarboxamido)‐2‐amino‐3 H ‐phenoxazin‐3‐one ( 4 ) [2].…”

“…The other nitrogen, resonating at 296 ppm, had only a single correlation to a doublet resonating at 7.58 ppm that was a part of the other three‐spin aromatic system. The downfield shift of the two nitrogen resonances is consistent with the sp 2 nitrogen of 4 that resonates at 293 ppm [2] The 1 H‐ 15 N long‐range data suggested a benzoxazinophenoxazine structure for the impurity. Linear and angular five, fused‐ring systems were considered but the latter could be ruled out when chemical shift considerations, long‐range 1 H‐ 13 C, and ROESY correlations were taken into account.…”

“…It is known that electron‐rich 2‐aminophenol derivatives can undergo catalytic oxidative cyclocondensation to form 2‐amino‐3 H ‐phenoxazin‐3‐one derivatives [1]. We previously reported the isolation and structure characterization of a highly colored bis‐( N,N‐ dimethylcarboxamido)‐2‐amino‐3 H ‐phenoxazin‐3‐one ( 4 ), presumably formed as an oxidative by‐product of the synthesis of 3‐amino‐ N,N‐ dimethylsalicylamide ( 3 ) as shown in Scheme [2]. The isolation of a stable and suitably pure sample of a somewhat less abundant, highly colored by‐product also formed in that reaction, 5 , proved to be chromatographically challenging.…”

“…This contention is supported by the observation that levels of both 4 and 5 increased when a solution of 3 in acetonitrile or ethanol was exposed to air over several days. Impurity 5 was also observed at an even higher level when 3 was treated with hydrogen peroxide in the presence of a selenium catalyst using the reaction conditions used to prepare 4 [2]. However, attempts to prepare 5 directly from 3 in appreciable yield were unsuccessful.…”

Synthesis of 7- and 8-Functionalized 2-Aminophenoxazinones via Cyclocondensation of 2-Aminophenols

“…Oxidative cyclizations mediated by hydrogen peroxide (H 2 O 2 ) in the presence of ebselen for the preparation of questiomycin A, its 1,9-dimethyl derivative, and actinocine have been reported previously. Unfortunately, under the employed reaction conditions, the oxidation of 5-methyl-, 5-chloro-, 17 and 6-N,N-dimethylcarboxamide-2aminophenols 21 afforded the corresponding phenoxazinones in moderate yields.…”