Bromination of aromatic amines

SCHEME 185. Chlorination and bromination of aromatic amines, hydrocarbons and naphthols with in situ generated active halogen... 

For chlorination, the formation of the (7-complex would be expected to be the rate-determining step since the aromatic chlorination of other substrates does not appear to give rise to deuterium isotope effects (Baciocchi et al., 1960 de la Mare and Lomas, 1967). The effect of the experimental conditions on the rate-determining step in the aqueous bromination of aromatic amines has been investigated in detail by Dubois and his co-workers (Dubois et al., 1968a, b, c Dubois and Uzan, 1968). This work suggests that, for tertiary aromatic amines, the proton loss is fast for para-bromination but partly or wholly rate-determining for ortho-bromination. There is however some... 

Rate coefficients (k, eqn 39) for the para-bromination of aromatic amines... 

Dioxan Br2 is suitable for mild bromination of aromatic amines.499 This orange-yellow complex, m.p. 64°, is readily prepared by mixing equivalent amounts of dioxan and bromine and cooling the resulting warm mixture with... 

A Methylanthrapyridone and Its Derivatives. 6-Bromo-3-methylanthrapyridone [81-85-6] (75) is an important iatermediate for manufacturiag dyes soluble ia organic solvents. These solvent dyes are prepared by replacing the bromine atom with various kiads of aromatic amines. 6-Bromo-3-methylanthrapyridone is prepared from 1-methyl amino-4-bromoanthra quin one (43) by acetylation with acetic anhydride followed by ring closure ia alkaU. The startiag material of this route is anthraquiaoae-l-sulfonic acid (16). 

Our recent studies on effective bromination and oxidation using benzyltrimethylammonium tribromide (BTMA Br3), stable solid, are described. Those involve electrophilic bromination of aromatic compounds such as phenols, aromatic amines, aromatic ethers, acetanilides, arenes, and thiophene, a-bromination of arenes and acetophenones, and also bromo-addition to alkenes by the use of BTMA Br3. Furthermore, oxidation of alcohols, ethers, 1,4-benzenediols, hindered phenols, primary amines, hydrazo compounds, sulfides, and thiols, haloform reaction of methylketones, N-bromination of amides, Hofmann degradation of amides, and preparation of acylureas and carbamates by the use of BTMA Br3 are also presented. 

Berthelot et al. have already reported that the reaction of aromatic amines with tetrabutylammonium tribromide (TBA Br3) in chloroform gave p-selective bromo-substituted aromatic amines (ref. 10). We also carried out the bromination of... 

Among the most important indirect methods of analysis which employ redox reactions are the bromination procedures for the determination of aromatic amines, phenols, and other compounds which undergo stoichiometric bromine substitution or addition. Bromine may be liberated quantitatively by the acidification of a bromate-bromide solution mixed with the sample. The excess, unreacted bromine can then be determined by reaction with iodide ions to liberate iodine, followed by titration of the iodine with sodium thiosulphate. An interesting extension of the bromination method employs 8-hydroxyquinoline (oxine) to effect a separation of a metal by solvent extraction or precipitation. The metal-oxine complex can then be determined by bromine substitution. 

Most of the rate comparisons in the halogenation of aromatic amines refer to bromination rate coefficients for para-substitution are collected in Table 10. Further results for o/7/io-substitution are provided in the cited references. Some of the early calculation based on (39) and (40) may be in error, because it was not then realized that the appropriate acidity function in (40) depends on the structure of the substrate (cf. Bell and Ramsden., 1958 Bell and Ninkov, 1966). The appropriate acidity function was used for the results listed in Table 10 but it is still advisable for rate comparisons to be based on experiments carried out under the same conditions. 

Interaction within encounter pairs. The above arguments have assumed that there is no interaction between the components in the encounter pairs A. B and B.X (Scheme 3) but this is probably unrealistic. Stabilization of the encounter pair A. B by charge-transfer interaction should favour the pre-association path by reducing the value of k 3 and possibly also increasing that of k4 [cf. equation (46)].22 Thus, in the nitration of neutral amine molecules (X) by nitronium ions (B) in concentrated sulphuric acid, interaction between the components in the encounter pair ArNHJ.NOJ should increase the acidity of the N—H hydrogens and facilitate the formation of the free amine. In the bromination of aromatic compounds (B) by HOBr(A), interaction between the components should increase the concentration of the encounter pair ArH. HOBr and facilitate the protonation of the hypobromous acid. 

We haven t yet discussed amine protection (that will come later in this chapter) but, since it is the amino group s nucleophilicity that is the problem, it makes sense to react it with an acylating agent an amide is much less nucleophilic than an amine because the nitrogen s lone pair is involved in conjugation with the carbonyl group. The same method was used to reduce the nucleophilicity of aromatic amines in bromination (Chapter 22). The carboxylic acid also needs protecting, and it is made into an ethyl ester. 

Nitrogen in enamines plays the same role it does in the chemistry of aromatic amines—not surprisingly, when we realize that enamines are, after all, vinyl amines. (Remember the similarities between vinyl and aryl halides.) For example, bromination... 

End analysis by GC-MS of bromo and iodo derivatives of aromatic amines (Section III.B.4) show easily recognizable ions due to the presence of heavy atoms. A convenient alternative to GC-MS for end analysis of halogenated derivatives is by GC-ECD. The scanning mode acquisition MS of the brominated analytes show characteristic (n + 1)-multiplets with two mass unit separations for ions containing n Br atoms, stemming from the natural isotope distribution of this element. Analysis of halogenated derivatives showed that about 20 aromatic amines were present at ppb levels in industrial wastewater and ground water from a landfill and a former ammunition plant. In the latter case, most... 

The reactivity of aromatic amines towards halogens is reduced by salt formation (mineral acid medium), A-acylation, or JV-alkylation. Aqueous solutions of the amine hydrohalide are treated with the halogen or glacial acetic acid is used as solvent to which sodium acetate is added to bind the halogen acid formed. As with phenols, the formation of mono- and di-bromin-ated amines is of especial interest. 

The acetyl derivatives of aromatic amines are often used in the preparation of substitution-products of the amines. Aniline and its homo-logues are very reactive substances and, as a consequence, the reactions which they undergo with other compounds can not always be controlled Aniline, for example, is largely converted into tribromoaniline by bromine... 

Identification of Aromatic Amines.—Most aromatic amines are soluble in hydrochloric acid, and are precipitated from the solution of their salts so formed by bases. Aqueous solutions of the amines, even when very dilute, yield precipitates of bromine substitution-products when treated with bromine water. The reaction is not characteristic, however, as phenols act in a similar way. 

The change of the orientational control by amino substituents in acid media or on complex formation is obviously supported by the bromination of iV,i T-dimethylaniline in sulfuric acid containing silver sulfate, which produces 60% of 3-bromo- and 20% 4-bromo-iV,i T-dimethylaniline . This result, again seemed to suggest that the appreciable para product in acidic halogenation of aromatic amines may be due to an ion-pair mechanism or to partial dissociation to the free base . Yet the formation of para products in the presence of excess of strong Lewis or Bronsted acid with aniline, could hardly indicate the presence of free amine, and there is evidence that electrophilic bromine attack, at the meta as well as at the para positions, occurs on deactivated anilinium ions . 

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