Reactions of 4-halogeno-N,N-dimethylaniline-N-Oxide with hemoglobin

Summary

Incubation with ferrihemoglobin or ferricytochrome c transforms 4-bromo-N,N-dimethylaniline-N-oxide (BrDANO) into 4-bromo-N,N-dimethylaniline, 4-bromo-N-methylaniline, and 2-dimethylamino-5-bromo-phenol. In a secondary reaction 4-bromo-N′-(4-bromophenyl)-6-hydroxy-N,N,N′-trimethyl-1,3-phenylenediamine (U) was formed from 2-dimethylamino-5-bromo-phenol and 4-bromo-N-methylaniline. The products were isolated and identified, the structure of (U) was elucidated.

It has been found that the formation of ferrihemoglobin by BrDANO is an autocatalytic reaction, ferrihemoglobin being the catalyst. BrDANO reacts with the catalyst resulting in the named products. 2-Dimethylamino-5-bromo-phenol oxidizes hemoglobin in the presence of oxygen. Thereby the catalyst ferrihemoglobin increases, which in turn increases the transformation of BrDANO to ferrihemoglobin forming derivates, This cycle explains the autocatalytic character of the production of ferrihemoglobin by BrDANO. The primary products of the reaction between 4-fluoro-N,N-dimethylaniline-N-oxide (FDANO) or 4-chloro-N,N-dimethylaniline-N-oxide (ClDANO) with cytochrome c, 4-fluoro- and 4-chloro-N,N-dimethylaniline, 4-fluoro- and 4-chloro-N-methylaniline, 2-dimethylamino-5-fluorophenol, and 2-dimethylamino-5-chloro-phenol were isolated and identified. The reactions between N,N-dimethylaniline-N-oxide (DANO), BrDANO, ClDANO, FDANO, and hemoglobin from blood of various species were studied. BrDANO and ClDANO accelerate the formation of ferrihemoglobin in solutions of hemoglobin from beef and dog blood much more effectively than DANO and FDANO.