Toluidine, ring-methylation

Toluidine is methylated in the ring by methanol and hydrogen chloride under pressure 661 aniline can also be alkylated in the ring by alcohols 662 and so can indoles by alcohols containing alkoxides at 220° under pressure.663... 

The technical preparation of crystal violet and of its methyl-free parent substance, parafuchsine, almost the oldest of the triphenylmethane dyes, is not so easily explained. As is well known, in this process aniline and p-toluidine are united by oxidation in an acid melt. (In the preparation of fuchsine itself, which contains a methyl group attached to one of the benzene rings, o-toluidine is an additional ingredient.) Although all the phases of this important synthesis have not yet been experimentally established, we may nevertheless explain it on the basis of a dehydrogenation similar to that involved in the formation of malachite green. Moreover, the union of several molecules of base proceeds exactly according to the principle on which indamines are formed (p. 321) (Bucherer). 

Mechanisms involving glycol bond fission have been proposed for the oxidation of vicinal diols, and hydride transfer for other diols in the oxidation of diols by bromine in acid solution.The kinetics of oxidation of some five-ring heterocyclic aldehydes by acidic bromate have been studied. The reaction of phenothiazin-5-ium 3-amino-7-dimethylamino-2-methyl chloride (toluidine blue) with acidic bromate has been studied. Kinetic studies revealed an initial induction period before the rapid consumption of substrate and this is accounted for by a mechanism in which bromide ion is converted into the active bromate and hyperbromous acid during induction and the substrate is converted into the demethylated sulfoxide. 

Cognate preparation, o-Tolunitrile. The preparation is similar to that described for p-tolunitrile except that p-toluidine is replaced by o-toluidine. The o-tolunitrile is isolated by steam distillation the oil, which may be dissolved in a little toluene, is distilled. The o-tolunitrile passes over as an almost colourless liquid at 94-96 °C/20 mmHg. Note the i.r. absorption (thin film) at c. 2200 (CN) and 760cm-1 (4 adj. H s) together with the expected aromatic ring and methyl group absorptions. The p.m.r. spectrum (CDC13, TMS) has <5 2.51 (s, 3H, Me), and 7.02-7.66 (m, 4H, CAr—H). 

Studies (2, 3) have also been reported of the reaction of phosphorus trichloride with diarylamines containing p-methyl or p-chloro substituents. In every case, the expected ring-substituted derivatives of 1 and 2 were obtained after the reaction mixture was treated with water. The interaction of (V-phenyl-o-toluidine and phosphorus trichloride at 200°C also gave a reaction mixture from which the expected phosphine oxide was isolated (3). None of the corresponding spirophosphonium chloride, however, could be obtained. The failure to isolate this substance can not be explained simply by the presence of an ortho substituent in the diarylamine, since it had been previously found that a 34% yield of a spirophosphonium chloride can be obtained via the interaction of fl/-phenyl-l-naphthylamine and phosphorus trichloride (2). No dihydropheno-phosphazine derivatives at all were obtained by the interaction of di-o-tolylamine and phosphorus trichloride at 200°C (3). 

Webster 82 described the preparation of a water-soluble tritriptycene and examined the NMR chemical shift changes of various substrates due to interactions with the aromatic ring currents. For example, a D20 solution of the tritritycene and p-toluidine exhibited an up-field shift (Av = 55 Hz) for the substrate methyl group absorption. 

On treating toluidine blue (144) with thionyl chloride, not only does ring chlorination take place, but also the 2-methyl is converted into a chloromethyl group (145). ... 

Staggered configurations have also been observed for the tricarbonyl chromium complexes of phenanthrene 294, 295), 9,10-dihydro-phenanthrene 293, 295), anthracene 202), naphthalene 262), and 1-aminonaphthalene 58). The eclipsed configuration has been observed for the tricarbonyl complexes of anisole (57, 229), toluidine 60, 61), methylbenzoate (59), o-methoxyacetylbenzene, o-hydroxyacetylbenzene 101), 2-methoxy-[l-hydroxy-ethyl]benzene (99), and 2-methyl-[l-hydroxy-l-phenylpropyl]benzene (97). It is apparent that the orientation of the chromium tricarbonyl moiety is in many cases controlled by the substituents on the ring to which it is coordinated, and this has been attributed to mesomeric electron repulsion or withdrawal by the substituents 374). 

Not only simple iV-alkyl-iV-nitr osoanilines 303,308 undergo this reaction, but also ring-substituted aniline derivatives with a free />ara-position, such as iV-ethyl-jV-nitroso-n-toluidine,303 m-chloro- and m-bromo-iV-methyl-jV-nitro-soaniline,310 and iV-methyl-JV-nitrosoanthranilic acid 301,311 the C-nitroso derivative obtained from the last-mentioned compound can be hydrolysed to nitrosalicylic acid.312 Rearrangements of the derivatives of 1- and 2-naph-thylamine have been reported by several authors.305,308,309,313... 

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