N-Hydroxy-2-naphthylamine

The role of N-sulfonyloxy arylamines as ultimate carcinogens appears to be limited. For N-hydroxy-2-naphthylamine, conversion by rat hepatic sulfotransferase to a N-sulfonyloxy metabolite results primarily in decomposition to 2-amino-l-naphthol and 1-sulfonyloxy-2-naphthylamine which are also major urinary metabolites and reaction with added nucleophiles is very low, which suggests an overall detoxification process (9,17). However, for 4-aminoazobenzene and N-hydroxy-AAF, which are potent hepatocarcinogens in the newborn mouse, evidence has been presented that strongly implicates their N-sulfonyloxy arylamine esters as ultimate hepatocarcinogens in this species (10,104). This includes the inhibition of arylamine-DNA adduct formation and tumorigenesis by the sulfotransferase inhibitor pentachlorophenol, the reduced tumor incidence in brachymorphic mice that are deficient in PAPS biosynthesis (10,115), and the relatively low O-acetyltransferase activity of mouse liver for N-hydroxy-4-aminoazobenzene and N-OH-AF (7,114,115). 

K5. Kaneko, M., and Leadon, S. A., Production of thymine glycols in DNA by N-hydroxy-2-naphthylamine as detected by monoclonal antibody. Cancer Res. 46, 71-75 (1986). 

The mechanism of chronic toxicity is related, but not identical. 2NA and other aromatic amines including benzidine and 4-aminobiphenyl are potent human urinary bladder carcinogens. Apparently the AT-hydroxy-2-naphthylamine is N-glucuronide and the product is transported from the liver to the urinary bladder, where the glucuronide can be hydrolyzed liberating N-hydroxy aromatic amine. This material is... 

Figure 2. The gel (%) and polymerization (O) times of unsaturated polyester containing a fixed initial concentration (in mol/L) of benzoyl peroxide and aryl-substituted N,N-bis(3-allyloxy-2-hydroxy-propyl)aniline versus the (t+ value of the aryl substituent of the amine. The symbols (A, A) indicate the corresponding time values for the analogous N-substituted 2-naphthylamine which in the usual sense is not a substituted aniline. (Time values from Refs. 24 and 25 (t+ from Ref. 23, except for (t+ value for 2-naphthyl (—0.61), recalculated from Bier (64).)...

N Phenyl 7-anilino-2-naphthol, phenyl-7-hydroxy-2-naphthylamine Needles. M.p. 160°. 

Thus, sulfate conjugation and acetylation may be involved in the metabolic activation of N-hydroxy aromatic amines, glutathione conjugation may be important in the nephrotoxicity of compounds, methylation in metal toxicity, glucuronidation in the carcinogenicity of p-naphthylamine and 3, 2 -dimethyl-4-aminobiphenyl. 

Fig. 2. Coupling components in azo dyes. The preferred positions of coupling are indicated by arrows and the usual pH conditions are noted. (1) 1-Naphthol [90-15-3], (2) 2-naphthol [135-19-3] (3) 3-hydroxy-2-naphthanilide [92-77-3], (4) aceto acetanilide [102-01-2] (5) 3-methyl-l-phenyl-5-pyrazoline [89-25-8] (enol form) (6) 8-amino-l-naphtol-3,6-disulfonic acid [90-20-0] (H-acid) (7) phenol [108-95-2] (8) resorcinol [108-46-3] (1 and 2 indicate the first and second substitution sites) (9) 2-naphthylamine [91-59-8] (10) 1-naphthylamine [134-32-7], (11) N,N-dimethylaniline [121 -69-7] (12) barbituric acid [67-52-7] (13) Fischer s base [118-12-7] (14) 8-hydroxyquinoline [148-24-3] (15) 2,4-dihydroxyquinoline [86-95-3],...

Amido -R -Acid. 3-A mi no-2.7-nupht ha l enedi sulfonic add 2-naphthylamine-3,6-disulfonic acid. C H,-NOA mol wt 303.32. C 39.60%, H 2.99%, N 4.62%, O 31.65%, S 21.14%, Prepd by treating 2-hydroxy-3,6-naph-thalenedisulfonie acid with ammonium sulfite and ammonium hydroxide Pelitcolas, Josue. Bull. She. Chim. France 1952, 89. 

Naphthalenedisulfonic acid, 4-((4-anilino-5-sulfo-1-naphthyl) azo)-5-hydroxy-, trisodium salt 1-Naphthol-3,6-disulfonic acid-8-azo-4 -[N-phenyl-1 -naphthylamine]-8 -sulfonic acid trisodium salt Sodium anazolene Trisodium 4 -anilino-8-hydroxy-1,1 -azonaphthalene-3,6,5 -trisulfonate... 

Evidently, the stability of 3-hydroxy-3,4-dihydroisoquinolines 137, formed as the result of heterocyclization, is also determined by the anne-lated benzenoid ring. The lower tendency toward aromatization for these compounds, compared to monocyclic analogs, leads to the ability of 137 to react as a cyclic azomethine. The addition of a molecule of nucleophile to the C=N bond causes opening of the isoquinoline ring and formation of a new ring system (for instance, a-naphthols 141 in alkaline aqueous solutions). Such conversions occur even under conditions of the recyclization reaction of 2-benzopyrylium salts, namely, on heating 137 in alcoholic ammonia a mixture of isoquinoline 138 and a-naphthylamine 140 results (88MI1). 

Phenothiazine N-Phenyl-N -(1-methylheptyl)-p-phenylenediamine Phenyl-a-naphthylamine Phenyl-P-naphthylamine N-Phenyl-N -(p-toluenesulfonyl)-p-phenylenediamine Stearoyl p-aminophenol Styrenated diphenylamine 4,4 -Thiobis-6-(t-butyl-m-cresol) 4,4 -Thiobis (6-t-butyl-o-cresol) 2,2 -Thiobis-(6-t-butyl-4-methylphenol) Thiodiethylene bis (3,5-di-t-butyl-4-hydroxy) hydrocinnamate Thiophenol Tris (3,5-di-t-butyl-4-hydroxybenzyl) isocyanurate 1,1,3-Tris (2-methyl-4-hydroxy-5-t-butylphenyl) butane Tris (nonylphenyl) phosphite... 

Shlyapnikov et al. [929] have reported distillation in vacuo at different temperatures (from 20° to 200°C), with indications of the degree of extraction from 0.02-0.1 g PE for 0.2-2.0% diphenylamine, phenyl-a-naphthylamine (Neozon A), phenyl-jS-naphthylamine (Neozon D), A-phenyl-A -cyclo-hexyl-p-phenylenediamine, A,A -di-/3-naphthyl-p-phenylenediamine, lonol, 2,4,6-tri-f-butylphenol, propyl gallate, a-naphthene, 2,2 -methylenebis(4-methyl-6-f-butylphenol), 2,2 -thiobis(4-methyl-6-f-butylphenol), 2,2 -methylenebis(4-chloro-6-f-butyl-phenol), 2,6-bis(2-hydroxy-3-f-butyl-5 -methylben-zyl)-4-methylphenol, and Tinuvin 326 reported accuracy of 1-2% using derivative (n = 2) UV spectrophotometry. 

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