Diazo coupling, aromatic compounds

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

Z)-compounds are formed in reactions with hydroxide, methoxide, cyanide, and sulfite ions, whereas (ii)-compounds are formed in most reactions with amines (formation of triazenes) and with diazo coupling components such as phenols and aromatic tertiary amines. 

The difference in position of attack on primary and secondary aromatic amines, compared with phenols, probably reflects the relative electron-density of the various positions in the former compounds exerting the controlling influence for, in contrast to a number of other aromatic electrophilic substitution reactions, diazo coupling is sensitive to relatively small differences in electron density (reflecting the rather low ability as an electrophile of PhN2 ). Similar differences in electron-density do of course occur in phenols but here control over the position of attack is exerted more by the relative strengths of the bonds formed in the two products in the two alternative coupled products derivable from amines, this latter difference is much less marked. 

Amino-l,2,4-thiadiazoles (129) are diazotised at — 10°C in phosphoric acid, and couple in the usual way with reactive aromatic compounds such as naphthol, giving moderate yields of diazo dyes <82AHC(32)285>. Diazotization of (129) (R = H and Ph) may be accomplished using aqueous sodium nitrite and hydrochloric acid. Treatment of the resulting salt with sodium azide yields the 3-azido derivative (130) (Equation (17)) <86CC800>. 

Azo or diazene compounds possess the —N=N— grouping. Aliphatic azo compounds of the type R—N=N—H appear to be highly unstable and decompose to R—H and nitrogen. Derivatives of the type R—N=N—R are much more stable and can be prepared as mentioned above by oxidation of the corresponding hydrazines. Aromatic azo compounds are available in considerable profusion from diazo coupling reactions (Section 23-IOC) and are of commercial importance as dyes and coloring materials. 

The reaction of an azepinium ion (3), generated in situ, with a number of aromatic substrates (benzene, anisole, phenol, furan and thiophene) usually gave aryl-2//-azepines [e.g. (4) from benzene] as the major products.7 In the case of reaction with pyrrole, however, a ring-opened compound (5) was the major product. Some condensed thiophenes have been shown8 to give products of substitution at C(l). For example, (6a) gave (6b) on diazo coupling. 

Diazonium Salts as Electrophiles Diazo Coupling Arenediazonium ions act as weak electrophiles in electrophilic aromatic substitutions. The products have the structure Ar—N=N—Ar, containing the —N=N— azo linkage. For this reason, the products are called azo compounds, and the reaction is called diazo coupling. Because they are weak electrophiles, diazonium salts react only with strongly activated rings (such as derivatives of aniline and phenol). 

Azo compounds bring two substituted aromatic rings into conjugation with an azo group, which is a strong chromophore. Therefore, most azo compounds are strongly colored, and they make excellent dyes, known as azo dyes. Many common azo dyes are made by diazo coupling. 

Less forcing conditions with organic peracids or Caro s acid can be used to make nitroso compounds.323 Although, as mentioned earlier, a low excess of oxidant can be used deliberately to give the diazo-coupled material as the major product,324 this can react further to the azoxy compound, but the latter is then hard to oxidize.325 Aliphatic primary amines are more difficult to oxidize compared to the aromatics, but use of peracetic acid in a solvent will lead to the formation of nitro compounds.322... 

Aromatic compounds which contain two amino groups, two hydroxyl groups, or one amino group and one hydroxyl group, located para or ortho to each other, are not suitable as coupling components. These compounds reduce diazo compounds, being oxidized to quinones in the process. (Smooth coupling may be achieved in many cases by the addition of thiosulfates or thiocyanates. )... 

Arenediazonium ions are weak electrophiles they react with highly reactive aromatic compounds—with phenols and tertiary arylamines—to yield azo compounds. This electrophilic aromatic substitution is often called a diazo coupling reaction. 

Azo compounds have the general formula R -N=N-R, where R and R are alkyl or aryl groups. Aromatic azo compounds are generally strongly colored and many are easily prepared via a so-called diazo coupling reaction, in which a diazonium cation is coupled with a relatively active (i.e., highly nucleophilic) arene such as a phenol or aniline. The dye called aniline yellow, for example, is prepared as follows ... 

The nitrogen atoms are retained in the product. This electrophilic aromatic substitution reaction is called diazo coupling, because in the product, two aromatic rings are coupled by the azo, or —N=N—, group. Para coupling is preferred, as in eq. 11.34, but if the para position is blocked by another substituent, ortho coupling can occur. All azo compounds are colored, and many are used commercially as dyes for cloth and in (film-based) color photography ... 

Diazo coupling is an electrophilic aromatic substitution reaction in which phenols and aromatic amines react with aryldiazonium eiectrophiles to give azo compounds. 

Compounds containing an azo linkage are most commonly produced by diazo coupling reactions (equation 20) and by oxidation of hydrazines (equation 21) or primary aromatic amines (equation 22). 

A good example of behaviour of this kind is provided by the ionization of carbonyl compounds (equation 6), to which additional data for proton transfer from nitroalkanes to various bases may be added [13, 14]. The isotope effect on these reactions rises to a maximum of 10 at AG° = 0, just where the Bronsted exponent is one-half, and it falls off to considerably lower values on either side of this point. The endothermic side of AG° = 0 is particularly well documented here kyjk-o drops to about 3 when AG° 25 kcal mole" and the Bronsted exponent becomes ca. 0.9. Aromatic hydrogen exchange shows a similar correspondence between isotope effect [15] and Bronsted exponent [16], and additional examples may be found in the hydrolysis of vinyl ethers [17] and diazocompounds [18], as well as in the diazo-coupling reaction [19]. 

The effect of micromixing was also observed for diazo coupling of electron-rich aromatic compounds and diazonium ions (Fig. 7.13) [12, 13] and [4 + 2] cycloaddition reaction of A -acyliminium ions and alkenes (Fig. 7.14) [14]. In the latter case, the second-stage reaction leads to polymerization, which will be discussed in Chap. 10. 

The most important reaction of the diazonium salts is the condensation with phenols or aromatic amines to form the intensely coloured azo compounds. The phenol or amine is called the secondary component, and the process of coupling with a diazonium salt is the basis of manufacture of all the azo dyestuffs. The entering azo group goes into the p-position of the benzene ring if this is free, otherwise it takes up the o-position, e.g. diazotized aniline coupled with phenol gives benzeneazophenol. When only half a molecular proportion of nitrous acid is used in the diazotization of an aromatic amine a diazo-amino compound is formed. 

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