Coupling reactions between reduced intermediates of insensitive munitions compound analog 4-nitroanisole

Warren M. Kadoya, Reyes Sierra-Alvarez, Bhumasamudram Jagadish, Stanley Wong, Leif Abrell, Eugene A. Mash, Jim A. Field

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Explosives, pesticides, and pharmaceuticals contain toxic nitroaromatic compounds that may form even more toxic azo compounds if they encounter reducing conditions in the environment. We investigated the mechanism by which 4,4′-dimethoxyazobenzene forms in anaerobic sludge incubations of 4-nitroanisole, an analog for the insensitive munitions compound 2,4-dinitroanisole (DNAN). Because studies have reported the mechanism to involve the coupling of reduced nitroaromatic intermediates, specifically aromatic amines and nitrosoaromatics, by nucleophilic processes, we abiotically paired 10 mM 4-aminoanisole with 2 mM 4-nitrosoanisole in nitrogen-flushed microcosms. However, only 7 μM of 4,4′-dimethoxyazobenzene had formed after 24 h. We identified the major product to be 4-methoxy-4′-nitrosodiphenylamine. Repeating this experiment in phosphate buffer at pH 5.1, 7.1, and 8.6 demonstrated that the formation of this unexpected product is acid catalyzed. We found that 4-methoxy-4′-nitrosodiphenylamine is more toxic than 4,4′-dimethoxyazobenzene to the bioluminescent bacterium Aliivibrio fischeri, with IC50 values of 0.1 μM and 0.5 μM, respectively. Both products are several orders of magnitude more toxic than reduced 4-nitroanisole intermediates 4-aminoanisole and 4-nitrosoanisole, as well as DNAN and its aromatic amine metabolites. Six-fold more 4,4′-dimethoxyazobenzene formed when we incubated 4-nitrosoanisole with ascorbic acid, a reducing agent, than when we incubated 4-nitrosoanisole with 4-aminoanisole in the absence of ascorbic acid. We therefore suspect that 4-hydroxylaminoanisole, the first reduction product of 4-nitrosoanisole, is a better nucleophile than 4-aminoanisole and couples more readily with 4-nitrosoanisole. Slightly basic and reducing conditions can prevent the formation and persistence of toxic coupling products on sites contaminated with nitroaromatics, i.e. DNAN-contaminated firing ranges.

Original languageEnglish (US)
Pages (from-to)789-796
Number of pages8
StatePublished - May 2019


  • 2,4-Dinitroanisole (DNAN)
  • Aromatic amines
  • Azobenzenes
  • Insensitive munitions compound
  • Nitroaromatics
  • Nitrosoaromatics

ASJC Scopus subject areas

  • General Chemistry
  • Public Health, Environmental and Occupational Health
  • Pollution
  • Health, Toxicology and Mutagenesis
  • Environmental Engineering
  • Environmental Chemistry


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