Diazo coupling amines

Diazonium salts are important intermediates in organic synthesis, e.g. for the Sandmeyer reaction. The most important use is the coupling reaction with phenols or aromatic amines to yield azo dyes (see Diazo coupling). 

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. 

The reactivity to diazo coupling of the 5-position of 2-aminothiophene and the 2-position in 3-aminothiophene complicates the formation of diazonium salts from these amines. However, high yields of azo compounds have been reported from 2-thienyldiazonium chloride prepared from the tin double salt (63AHC(l)l). Aminothiophenes substituted with electron-withdrawing groups are easily diazotized and coupled with dimethylaniline, /3-naphthol, etc. (Section 3.14.2.4). 

The pH used for diazo coupling of amines is very important in determining the nature of the products. Under near-neutral conditions the diazonium ion may attack the nitrogen of the arenamine rather than a ring carbon. In this event a diazoamino compound, a triazene, —N=N—N—, is formed ... 

By choice of reaction conditions so as to avoid nucleophilic substitution, the diazonium salt from the 3-amine (126) will undergo diazo coupling to form azo dyes (79BRP1550828). 

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... 

Thionyl chloride can be used to activate surface carboxylic groups for subsequent modification with amines and esters. This approach has been used with oxidized carbon surfaces [23, 24] and for the activation of poly(acrylic) acid surfaces prior to diazo coupling [25] (see figure 6.6). 

Zollinger and coworkers" " have also studied the diazo coupling reactions of diazo-nium salts extensively. The proposed mechanism for the N-coupling reaction between a diazonium ion and an aromatic amine involves formation of an amine-diazonium ion complex, 9, which is converted into a cr-complex, 10, which subsequently loses a proton to base forming the product (equation 43), where B is any base, i.e. the amine, the solvent or... 

In fact, when either chloride ion or water is added to the reaction mixture, both the rate and the product composition change markedly. For example, the rate increases by fourteen times and the product composition changes from 9% of the N-coupled diazoamino compound to 79% of the diazoamino compound when the chloride ion concentration is increased from zero to 1.4 x 10" M. The amount of the N-coupled diazoamino product also increased at all three temperatures used in the study as the amount of amine (base) increased. On the basis of the base catalysis and the hydrogen-deuterium kinetic isotope effects and their studies of other diazo coupling reactions, the authors concluded that the N-coupling and the C-coupling reactions both proceed by an S 2 mechanism with the proton transfer from the cr-complex rate-determining. The results are best explained by the mechanism presented in Scheme 3. 

Cope elimination A variation of the Hofmann elimination, where a tertiary amine oxide eliminates to an alkene with a hydroxylamine serving as the leaving group, (p. 900) diazo coupling The use of a diazonium salt as an electrophile in electrophilic aromatic substitution. (p. 907)... 

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

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