Toluidine o- and

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). 

Waldschmidt-Leitz and Kuhn studied in detail the synthesis of hippurylanilide—the type of synthesis first foimd by Bergmann and associates. Using nearly equivalent amounts of hippuric acid and aniline, with papain as enzyme, there was 94% synthesis of the anilide. The equilibrium was approached from both sides. They could not obtain synthesis of hippurylamide from hippuric acid and ammonia the amide was completely and rapidly hydrolyzed. The condensation with hippuric acid occurred with aniline, o- m-, and p-toluidine, o- and p-aminophenol, o-anisidine, p-aminobenzoic acid, sulfanilamide, and o- and p-phenylene-diamine. The following compounds were inactive JV-methylaniline, o-aminobenzoic acid, sulfanilic acid, a-aminopyridine, adenine, benzyl-amine, cyclohexamine, and ammonia. 

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. 

Uses. (9-Nitrotoluene is used in the synthesis of intermediates for azo dyes, sulfur dyes, mbber chemicals, and agriculture chemicals. Typical intermediates are o-toluidine, o-nitrobenzaldehyde, 2-nitro-4-chlorotoluene, 2-nitro-6-chlorotoluene, 2-amino-4-chlorotoluene (Fast Scarlet TR Base), and 2-amino-6-chlorotoluene (Fast Red KB Base). -Nitrotoluene is used principally in the production of intermediates for azo and sulfur dyes. Typical intermediates are -toluidine, -nitrobenzaldehyde, and 4-nitro-2-chlorotoluene. 

The foinialion of iosaniiine fioni a mi tuie of aniline, o- and / -toluidine is represented by assiiining that the methyl-gioup of /-toluidine acts as the link which connects the nuclei of aniline and n-toiuidine. 

While the direct halogenation of toluene gives a mixture of isomers that is difficult to separate into the pure isomers, the isomeric o- and /r-nitrotoluenes 6a and 6b, formed by nitration, are easy to separate from each other. Thus reduction of the single o- or /j-nitrotoluene 6 to the o- or /j-toluidine 7a or 7b respectively, followed by conversion into the corresponding diazonium salt 8 and a subsequent Sandmeyer reaction leads to the pure o- or /j-halotoluene 9. 

When HCl salts of arylalkylamines are heated at 200-300°C, migration occurs. This is called the Hofmann-Martius reaction. It is an intermolecular reaction, since crossing is found. For example, methylanilinium bromide gave not only the normal products o- and p-toluidine but also aniline and di- and trimethylanilines." As would be expected for an intermolecular process, there is isomerization when R is primary. 

Methaqualone is being widely abused by youths in this country. Recently, in the northeast, some abusers were stricken with severe side effects, including bloody urine and gastrointestinal cramps. The tablets were found to be of clandestine manufacture.They contained fairly large amounts of impurities from a poor synthesis. The impurities were o-toluidine, o-aminobenzoic acid, and o-methyl acetanilide—again proving the old proverb Let the buyer beware. ... 

Chemical/Physical. Kanno et al. (1982) studied the aqueous reaction of o-toluidine and other substituted aromatic hydrocarbons (aniline, toluidine, 1- and 2-naphthylamine, phenol, cresol, pyrocatechol, resorcinol, hydroquinone, and 1-naphthol) with hypochlorous acid in the presence of ammonium ion. They reported that the aromatic ring was not chlorinated as expected but was cleaved by chloramine forming cyanogen chloride. As the pH was lowered, the amount of cyanogen chloride formed increased (Kanno et al., 1982). 

Chemical/Physical. The following compounds were identified as metabolites in rice plants after treatment with chlorphenamidine 7V-(4-chloro-o-tolyl)-7V-methyl formamidine, 7V-formyl-4-chloro-o toluidine, and 4-chloro-o toluidine (Lizuka and Masuda, 1979). 

Hecht SS et al Comparative carcinogenicity of o-toluidine hydrochloride and nitroso-toluene in F-344 Rats. Cancer Lett 16 103-108, 1982... 

Pendergrass SM An approach for estimating workplace exposure to o-toluidine, aniline, and nitrobenzene. Am Ind Hyg Assoc J 55 733-737, 1994... 

CH,. CO. NH. CeH,(CH,). N2. Br, prepd by Wallach from 2-amino-4-acetaminotoluene (Ref 3) and designated by him as acetpara-toluidine-o-diazobromide (Refs 1 2), is a yel solid which explodes on rapid heating. The chloride, designated as acetparatolu-idine-o-diazochloride and prepd from 4-acetaminotoluene-2-diazopiperidide (Ref 4), also explodes on heating... 

The first commercial synthetic dye, Mauveine (3), discovered by Perkin in 1856, was also a heterocycle, an azine of the Safranine class prepared by oxidation of aniline containing o- and p-toluidines. Since that time the contribution to colour chemistry from heterocyclic synthesis has been considerable and the present review can only hope to present some of the more salient features and at that only briefly. As an illustration it can be noted that since the late 1960s there have been in excess of 230 patents covering the use of azo dye couplers based on 2,6-dihydroxypyridine alone and the number of disclosures describing pyrazolones is probably greater than 1000. 

Dissolve 0.25 g benzoic acid and 0.29 g sodium benzoate in 200 ml water. Add 0.1 g toluidine blue O and stir (Feder and O Brien, 1968). Filter through an glass microfiber filter. Store up to several months at room temperature. Discard if a precipitate forms. 

If either the o- or -position is occupied, only one isomer is obtained transformation to the mefo-position does not occur. This is a standard method of preparation of acyl-amino-ketones, or by a further hydrolysis of amino-ketones. The tendency, illustrated in this reaction, of groups to wander from the amino group to the nucleus, is also shown in previous reactions and in the preparation of aminoazobenzene from diazoamino-benzene (Preparation 456), of sulphanilic acid from aniline sulphate (Preparation 292), of o- and p-chloroacetanilides from acetochloranilide (Preparation 328), of o- and p-toluidine from methylaniline hydrochloride, and of 1 2 4-aminodimethylbenzene (2 4-xylidine) from dimethylaniline hydrochloride. 

Separation of o- and p-Toluidine (a).—The oil is separated from the water, ice and salt added, and the mixture stirred. A whitish-yellow crystalline compound will appear, which is the hydrate of the p-compound. This is filtered through an ice filter (Fig. 4), and the hydrate well pressed... 

Commercially available o-toluidine, b.p. 75-77°/10 mm., is suitable. Redistillation of this material gave no significantly better results. The checkers obtained a 42% yield of 2-amino-3-nitrotoluene using practical o-toluidine directly, and a 57% yield after redistillation. 

---