95-53-4 o-Toluidine

Uses O-Toluidine is a light yellow to reddish-brown liquid. The compound quickly turns to a dark color on exposure to light and atmospheric air. The compound has extensive use in a number of industries around the world (e.g., as an intermediate in the manufacture of azo and indigo dyes, pigments, sulfur dyes, pesticides, pharmaceutical products, rubber and vulcanizing chemicals). 

Toxicity O-Toluidine is highly toxic to animals and humans and is rapidly absorbed by oral, dermal, and inhalation routes. The acute oral LD50 in rats ranges from 900 to 940 mg/kg.78,83 The compound is known to cause adverse effects in workers that include headache, irritation of skin, eye, kidneys, and bladder, and hematuria. O-Toluidine has caused hepatocellular adenomas and carcinomas in experimental mice and rats. 

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It is prepared by the direct nitration of toluene as a 50-60% component of the mixture of isomers. Used for the preparation of o-toluidine. 

Dissolve 2 3 drops of o toluidine in a few drops of dil. HCl and add 2 3 drops of ferric chloride solution a green coloration is produced and is slowly replaced by a bluish-green or blue precipitate. 

Green coloration. Catechol (colour rapidly darkens). [Aniline (pale green), o-toluidine (pale green initially), mono-methylaniline, and diphenylamine, each in dil. HCl.]... 

The production of diacetyl derivatives is facilitated by the presence of substituents in the ortho position thus an excellent yield of diacetyl-o-toluidine results when o-toluidine is heated with an excess of the reagent ... 

Boil a mixture of 10 g. (10 ml.) of o-toluidine and 38 g. (35 ml.) of acetic anhydride in a 75 or 100 ml. Claisen flask fitted with a reflux condenser (Fig. Ill, 28, 1, but with trap replaced by a calcium chloride or cotton wool guard tube) for 1 hour. Arrange the flask for distillation under reduced pressure (compare Fig. II, 20, 1) and distil acetic acid and the excess of acetic anhydride pass over first, followed by the diacetyl derivative at 152-153°/20 mm, some mono-acetyl-o-toluidine (1-2 g.) remains in the flask. The yield of diacetyl-o-toluidine is 14-15 g, it is a colourless, somewhat unstable hquid, which slowly sohdifies to yield crystals, m.p. 18°, To prepare the (mono-) acetyl-o-toluidine, warm a mixture of 5 g. 

In a 1 or 1-5 htre round-bottomed flask prepare a solution of 53-5 g. of o-toluidine in 170 ml. of 48 per cent, hydrobromic acid, cool to 5° by immersion in a bath of ice and salt. Diazotise by the gradual addition of a solution of 36 -5 g. of sodium nitrite in 50 ml. of water stopper the flask after each addition and shake until all red fumes are absorbed. Keep the temperature between 5° and 10°. When the diazotisation is complete, add 2 g. of copper powder or copper bronze, attach a reflux condenser to the flask, and heat very cautiously on a water bath. Immediately evolution of gas occurs, cool the flask in crushed ice unless the... 

A good 3ueld of 5-iodo-2-aminotoluene may be obtained by intimately mixing o-toluidine hydrochloride, iodine and calcium carbonate, and then adding water to the mixture. The liberated hydriodic acid reacts at once with the Calcium carbonate and the lij driodide of the base is not formed. 

Triturate 20 g. of dry o-toluidine hydrochloride and 35 5 g. of powdered iodine in a mortar and then grind in 17 -5 g. of precipitated calcium carbonate. Transfer the mixture to a conical flask, and add 100 ml. of distilled water with vigorous shaking of the flask. Allow the mixture to stand for 45 minutes with occasional agitation, then heat gradually to 60-70° for 5 minutes, and cool. Transfer the contents of the flask to a separatory funnel, extract the base with three 80 ml. portions of ether, diy the extract with anhydrous calcium chloride or magnesium sulphate, and remove the excess of solvent. The crude 5-iodo-2-aminotoluene separates in dark crystals. The yield is 32 g. Recrystallise from 50 per cent, alcohol nearly white crystals, m.p. 87°, are obtained. 

Methylaniline Ethylaniline n-Propylaniline n-Butylaniline Benzylaniline 2 -MethyIbenzylamine N-Ethylbenzylamine 2 -Methyl o-toluidine N-Methyl m-toluidine 2 -MethyI p-toluidine N-Ethyl o-toIuidine N-Ethyl m-toIuidine 2S -Ethyl p-toluidine 2 -MethyI a-naphthylamine N-Methyl p-naphthylamine N-Phenyl- a-naphthylamine 2 -Phenyl-P-naphthylamine... 

Prepare o-tolunitrile, b.p. 94-96°/20 mm., from o-toluidine following the method given in Section IV,66 under -Toluidine. Also prepare 600 g. of 75 per cent, sulphuric acid by adding 450 g, (245 ml.) of con-... 

Acetyl-o-toluidine Acetyl-m-tolnidine Acetyl-p-toluidine... 

One type of o-aminobenzyl anion synthon is a mixed Cu/Zn reagent which can be prepared from o-toluidines by / i.s-trimethylsilylation on nitrogen, benzylic bromination and reaction with Zn and CuCN[l]. Reaction of these reagents with acyl halides gives 2-substituted indoles. 

Reaction takes place on nitrogen when the electrophilic center is an sp carbon, particularly if it is charged. Thus Mannich reaction yields the N-substituted compound (71 and 72) (Scheme 34) (54. 157-159). The same reaction is reported with piperidine, o-toluidine. and methylaniline (158). 

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