O- and p-Toluidine

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). 

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. 

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. 

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... 

Similar reactions have been carried out with naphthalene and thiophene. The method has been employed only to a limited extent 23 since its discovery, probably because it involves the isolation of the dry diazonium salts and because a number of aryldiazonium salts (from o- and p-toluidine and /3-naphthylamine) gave no biaryls but only the corresponding aryl halides. 

Fierz-David and Ziegler (301) first applied this method to azo compounds. Ethyl acetoacetate and various aromatic amines (aniline, o- and p-toluidines, m-xylidine, o-anisidine, and chloroanilines) were convereted to acetoacetanilides and then coupled with diazotized sulfanilic acid. The azo dyes (38) were reduced with stannous chloride in hydrochloric acid to the corresponding aminoaceto-acetanilides (39), which in alkali formed the dihydropyrazines (40). Catalytic reduction of o-hydroxyphenylglyoxal phenylhydrazone in acetic acid over palladium has been shown also to give 2,5-bis(o-hydroxyphenyl)pyrazine (302). Reduction of chemical means has been shown to give... 

Craven studied the reactions of phenyl and o- and p-tolyl isocyanates with aniline, o- and p-toluidine and o-chloroaniline in dioxane solution mainly in the absence of catalysts. The reactivity in these systems agreed with the classical electronic picture according to which electron donating group that increase the nucleophilicity or base strength increase the reactivity of the amine. Substituents in ortho position, particularly on the isocyanate, cause steric hindrance and reduce the reactivity (see Table XIX). 

Deamination. A new deamination procedure involves precipitation of the aryl-diazonium hexafluoroborate, for example as described by Rutherford and Redmond, and spontaneous and exothermal decomposition of this salt in tetramethylurea, which functioned satisfactorily where other nonaqueous solvents failed. Yields are best (75-85%) when the aromatic ring carries an electron-withdrawing substituent (NOj, COjH, Br). In the case of aniline, o- and p- toluidine, and o-anisidine yields are in the range 25-30%. The dry salt is added to tetramethylurea in portions at room temperature, and the temperature is controlled to 65° when evolution of nitrogen has ceased, the solution is poured into water. 

To discover whether the apparent N-ortho-C exehange pattern in the transformation of aromatic amines to substituted pyridines also holds for other aromatic amines, we also studied the reactions of phenylenediamines, toluidines, naphthyl-amines, and anthracylamines [9]. Batch reactions of o-, m-, and p-toluidine resulted in low conversion, a factor of 2 to 4 higher than for aniline. Much of the conversion was, however, because of isomerization of one toluidine to the other two isomers, and to transmethylation to aniline and xylidines. The yield of substituted pyridines (lutidine and collidine) from o- and p-toluidine was, therefore, approximately as low as that for the aniline transformation. Conversion of m-tolui-dine to the substituted pyridine was much higher than that of its ortho and para isomers, however, just as nz-phenylenediamine results in much higher conversion to aminomethylpyridines than do o- and p-phenylenediamine. 

Following extensive studies, it turns out that Perkin s starting aniline was, in fact, contaminated with o- and p-toluidine impurities which proved critical in the formation of mauveine as shown in the column figure, mauveine actually constitutes a mixture of two compounds. ... 

When primary aromatic amines are used instead of tertiary amines the products of reaction are either azoxy compounds [186] or nitro compounds [187]. In the presence of soluble complexes of titanium, aniline, o- and p-toluidine and m-nitro aniline are oxidized by er -butyl hydroperoxide or cumyl hydroperoxide to the corresponding azoxy compounds in 92-99% yields [182], equation (129). 

It is interesting to note that the information provided in Figure 10.1, which represents, in outline, the creation of an industry, is a clear affirmation of previous comments (see, e.g.. Chapter 6, Scheme 6.93). As shown in Scheme 10.14, nitration of impure (contaminated by toluene) benzene, followed by iron and acetic acid nitro group reduction, produces both aminobenzene (aniline) and 2-and 4-methylaminobenzene (o- and p-toluidine, respectively). 

Scheme 10.14. The formation of aminobenzene (aniline) and o- and p-methylaminobenzenes (o- and p-toluidines) from the nitration of a mixture of benzene and methylbenzene (toluene) and subsequent reduction of the mixture with iron (Fe) in acetic acid (CH3CO2H).

Based on the experimental data, discuss the influence of the steric effects on the rate-determining step (rds) of the reaction with o- and p-toluidine, formulating the kinetic law for each case. 

---