4-Aminodiphenylamine Explained

4-Aminodiphenylamine is a diphenylamine with an additional amine substituent. This dimer of aniline has various industrial uses, including as a hair dye ingredient, but also has raised concerns about toxicity by skin contact.^[1] It is also a starting material for the synthesis of 6PPD, an antiozonant for various rubber products. A colorimetric test for the quantitative analysis of nitrite, at levels below 100 nanograms per milliliter, is based on nitrite-catalyzed coupling of 4-aminodiphenylamine with N,N-dimethylaniline.^[2]

Synthesis

The most common route of industrial production is by the metal catalysed reaction of aniline with 4‑nitrochlorobenzene to give 4‑nitrodiphenylamine (Buchwald–Hartwig amination):

Subsequent hydrogenation gives 4-aminodiphenylamine.^[3] An alternative is the direct reaction of nitrobenzene with aniline via a nucleophilic aromatic substitution of hydrogen (vicarious nucleophilic substitution).^{[4] [5]} This again requires a reduction step but is a good example of industrial green chemistry as it eliminates the need for organochlorine starting materials and metal catalysts.

Notes and References

1. Studies on the skin uptake and efflux kinetics of N-phenyl-p-phenylenediamine: an aromatic amine intermediate . S. K. . Khanna . Pushpa . Tewari . Anil . Joshi . G. B. . Singh . International Journal of Cosmetic Science . 9 . 3 . 1987 . 137–147 . 19456976 . 10.1111/j.1467-2494.1987.tb00470.x . 205555627 .
2. Sensitive flow injection colorimetry of nitrite by catalytic coupling of N-phenyl-p-phenylenediamine with N,N-dimethylaniline . Ryoichi . Kadowaki . Shigenori . Nakano . Takuji . Kawashima . Talanta . 1999 . 48 . 1 . 103–107 . 18967448 . 10.1016/s0039-9140(98)00227-6 .
3. Bochkarev . V.V. . Soroka . L.S. . Bashkin . J.K. . Resource-efficient technology to produce 4-aminodiphenylamine . Resource-Efficient Technologies . December 2016 . 2 . 4 . 215–224 . 10.1016/j.reffit.2016.10.011. free .
4. Stern . Michael K. . Hileman . Fredrick D. . Bashkin . James K. . The direct coupling of aniline and nitrobenzene: a new example of nucleophilic aromatic substitution for hydrogen . Journal of the American Chemical Society . November 1992 . 114 . 23 . 9237–9238 . 10.1021/ja00049a095.
5. Bashkin . James . Rains . Roger . Stern . Michael . Taking green chemistry from the laboratory to chemical plant . Green Chemistry . 1999 . 1 . 2 . G41 . 10.1039/GC990G41.