3- Anisidine

A significant increase in transitional cell carcinomas of the urinary bladder was found in mice and rats fed diets containing 5000mg/kg o-anisidine bydrocbloride for 103 weeks.  

Tbe lARC bas determined that there is sufficient evidence for the carcinogenicity of o-anisidine in experimental animals and that it is possibly carcinogenic to humans. Available data were inadequate to evaluate the carcinogenicity ofp-anisidine.  

The 2003 ACGIH threshold limit value-time-weighted average (TLV-TWA) for the 0- and p-isomers of anisidine is 0.1 ppm (0.5 mg/m ). 

Physical Form. o-Anisidine is a yellowish liquid that darkens on exposure to air p-anisidine is a white solid. 

In the preparation of azo dyes corrosion inhibitor chemical intermediate 

Commercial 98% anthracene is purified in 2-kg. lots by refluxing with 1.5% of its weight of sodium metal followed by distillation. Crystallization of the distillate from benzene gives anthracene melting at 215-217.5° in 60-70% yield. 

A mixture of 50 g. (0.3 mole) of pure anthracene, 30 ml. of oxalyl chloride (p. 242), and 150 ml. of dry nitrobenzene is heated under a reflux condenser in a metal bath. The temperature of the bath is raised from 120° to 240° over a period of 5-6 hours, after which the nitrobenzene is removed by steam distillation. The residue is treated with a solution of 40 g. of sodium hydroxide in 700 ml. of water, and the mixture is heated to reflux for 30 minutes. The mixture is filtered, and the cooled filtrate is extracted with petroleum ether (b.p. 30-60°), after which the aqueous solution is heated to boiling and treated with activated carbon. After filtration of the hot solution to remove the carbon, the carbon is washed with 2 N sodium carbonate solution, and the combined filtrate and washings are acidified to give 41.6 g. (67%) of 9-anthroic acid, m.p. 208-212°. 

Ten grams (0.094 mole) of benzaldehyde (free of benzoic acid) is added to a mixture of 10.6 g. (10% excess) of acetic anhydride and 0.1 g. of concentrated sulfuric acid. The mixture is agitated and cooled so the temperature does not rise above 70°. The mixture is allowed to stand 24 hours at room temperature. It is then dissolved in ether, and the resulting solution is extracted with water, dilute sodium carbonate solution, and again with water. After being dried over sodium sulfate the ethereal solution is distilled. There is obtained 16 g. (81%) of the diacetate, b.p. 154°/20 mm., m.p. 46°. 

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Acetyl-o-aniaidine Acetyl-m-anisidine Acetyl-p-anisldine Acetyl-o-phenetidine Acetyl-m-phenetidine Acetyl-p-phenetidine (or phenacetin) Acetyl-a-naph thy lam ine Acetyl- p-naphthylamine... 

The diazonium salts precursors can be aniline, o- and p-toluidine, o-and p-anisidine, o- and p-phenetidine. or 3-naphthy]amine. The resulting formazans are crystalline and inlensel> colored. They are soluble in organic solvents, giving a red-violet coloration that darkens to blue. Dehydrogeneration gives the corresponding tetrazolium salts, which are isolated as perbromides (Scheme 51. Table X-13). 

Titrimetric Methods. Frequently, the reduction of gold solutions leads to finely divided precipitates which are difficult to recover quantitatively. In such cases, the reduction of Au(III) to Au(0) by, eg, hydroquinone, can be followed potentiometricaHy (49). The end point in such titrations also can be determined with indicators such as benzidine (50) or o-anisidine (51). Alternatively, the reduction can be effected with excess hydroquinone which is then back-titrated with Ce(IV) (52). lodometric deterrnination of Au(III) also is useflil (53). 

Uses. (9-Nitrochlorobenzene is used in the synthesis of azo dye intermediates such as o-chloroaniline (Fast YeUow G Base), i9-nitroani1ine (Fast Orange GR Base), o-anisidine (Fast Red BB Base), o-phenetidine, and (9-aminophenol (see Azo dyes). It also is used in corrosion inhibitors, pigments, and agriculture chemicals. -Nitrochlorobenzene is used principally in the production of intermediates for azo and sulfur dyes. Other uses include pharmaceuticals (qv), photochemicals, mbber chemicals (qv), and insecticides (see Insectcontroltechnology). Typical intermediates manufactured from the para isomer are -lutioaruline (Fast Red GC Base), anisidine, -aminophenol, -nitrophenol, -phenylenediamine, 2-chloro-/)-anisidine (Fast Red R Base), 2,4-dinitrochlorobenzene, and l,2-dichloro-4-nitrobenzene. 

Important analogs of aniline include the toluidines, xyUdines, anisidines, phenetidines, and its chloro-, nitro-. A/-acetyl. A/-alkyl. A/-aryl. A/-acyl, and sulfonic acid derivatives. 

Fig. 5. Direct red dyes, (a) Direct Red 81 described ia text (68) (b) Direct Red 2 (o-toLidiae coupled to two moles of naphthionic acid) (69) (c) Direct Red 23 (aniline coupled to 6,6 -ureylenebis-l-naplitliol-3-sulfonic acid with a second coupling with j aminoacetanilide) (70) and Direct Red 80 (2 mol 6-amino-3,4 -azobenzenedisulfonic acid coupled twice to 6,6 -ureylenebis-l-naphthol-3-sulfonic acid) (73). Direct Red 24 (4-aniino-y -toluenesulfonic acid coupled under acidic conditions to 6,6 -ureylenebis-l-naphthol-3-sulfonic acid followed by an alkaline coupling of o-anisidine) (71) (d) Direct Red 72 (Broenner s acid, ie, 6-artiino-2-naphthalenesulfonic acid coupled under acidic conditions to 6,6 -ureylenebis-l-naphthol-3-sulfonic acid followed by an...

Guaiacols. Cresote, obtained from the pyrolysis of beechwood, and its active principles guaiacol [90-05-1] (1) and cresol [93-51-6] (2) have long been used ia expectorant mixtures. The compounds are usually classed as direct-acting or stimulant expectorants, but their mechanisms of action have not been well studied. Cresol is obtained by the Clemmensen reduction of vanillin (3), whereas guaiacol can be prepared by a number of methods including the mercuric oxide oxidation of lignin (qv) (4), the ziac chloride reduction of acetovanillone (5), and the diazotization and hydrolysis of o-anisidine (6). 

This group has been used extensively in /3-lactam syntheses, where it is used to introduce the nitrogen as p-anisidine. 

Lissapol LS (mainly sodium salt of anisidine sulfate) [28903-20-0J. Refluxed with 95% EtOH, then filtered to remove insoluble inorganic electrolytes. The alcohol solution was then concentrated and the residue was poured into dry acetone. The ppte was filtered off, washed in acetone and dried under vacuum. [Biswas and Mukerji J Phys Chem 64 1 I960],... 

The submitters have found that other arylamines may be employed in a similar manner in place of aniline. Thus N-2-cyanoethyl-/)-anisidine was obtained in 76% yield as plates,... 

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