Diazonium conjugation

The Mannich reaction provides an often-superior alternative to diazonium conjugation (Section 6.1, this chapter), because of the disadvantages inherent in the instability of both the diazonium group and the resultant diazo linkage. By contrast, conjugations done through Mannich condensations result in stable covalent bonds. 

Oxidative Couplings of Heterocyclic Hydrazones. This method has opened the way to the preparation of azo derivatives of diazo compounds unobtainable by other means, ie, heterocycHc compounds ia which the diazotizable amino group is conjugated with the heterocycHc nitrogen atom as ia 2- and 4-amiQopyridine, compounds which do not normally yield stable diazonium salts (38). The reaction occurs as illustrated by equation 7 for the iateraction of (A/-methylcarbostyryl)hydrazone [28219-37-6] and dimethyl aniline the overall process is oxidation. 

This diazotization is typical of many aminoazoles the diazonium ions formed are relatively strong acids. The pATa values of five di-, tri-, and tetrazolediazonium ions are reported to be between 3 and 4, i. e., about 10 units lower (more acidic) than those of the respective unsubstituted heterocycles (Vilarrasa et al., 1974). Therefore, deprotonation of the diazonium ion is easy and, depending on reaction conditions, yields either the diazonium salt or its conjugate base, the diazo compound. The electrophilic reactivity of the P nitrogen atom in the diazo group of the base is lower than the reactivity of the diazonio group of the cation (Diener and Zollinger, 1986 see Sec. 12.2). 

Despite these critical remarks, this discussion may be summarized by saying that the participation of the nitrosoamine (3.7), of its conjugate O-acid (3.8), of the (Z)-or (i -diazohydroxide (3.9), and of their conjugate acids (3.10) in the system of Scheme 3-36 remains more or less conjectural, but at least the nitrosoamine (3.7) does appear to be reasonable well documented as an intermediate on the pathway to the diazonium ion. 

According to Scheme 5-4 the diazonium ion (as a Lewis acid) is in equilibrium with its conjugate base, the diazohydroxide, and according to Scheme 5-5 the diazohydroxide (this time as acid) is in equilibrium with its conjugate base, the diazoate. This treatment applies only to those reaction steps that are moderately or very rapid and are reversible. 

Basically the kinetic results are consistent with the first (rapid) reaction being the addition of a hydroxide ion to the diazonium ion followed by the very fast deprotonation of the (Z)-diazohydroxide to give the (Z)-diazoate (steps 1 and 2 in Scheme 5-14). In addition, however, the stopped-flow experiments showed that the diazonium ion also reacts with the water molecule, initially forming the conjugate acid of the (Z)-diazohydroxide (ArN2OH2), which is then very rapidly deprotonated (reaction 1 in Scheme 5-14). The rate of the relatively slow (Z/E)-isomerization (reaction 5 in Scheme 5-14) can in general be measured by conventional spectrophotometry. 

It becomes clear that in all these compounds it is the conjugate base that takes part in the substitution proper. For mono- and particularly 1,3-dicarbonyl compounds this result actually removes the problem of whether it is the keto or the enol form which enters into an electrophilic substitution by diazonium ions, halogenating agents, and many other reagents. The keto and the enol form are distinct species, but they have one (common) conjugate base This was made clear quite early, but even today there are many chemists who seem not to be aware of it. 

Meerwein Arylation Reactions. Aryl diazonium ions can also be used to form certain types of carbon-carbon bonds. The copper-catalyzed reaction of diazonium ions with conjugated alkenes results in arylation of the alkene, known as the Meerwein arylation reaction.114 The reaction sequence is initiated by reduction of the diazonium ion by Cu(I). The aryl radical adds to the alkene to give a new (3-aryl radical. The final step is a ligand transfer that takes place in the copper coordination sphere. An alternative course is oxidation-deprotonation, which gives a styrene derivative. 

Crosslinking using diazonium compounds usually creates deeply colored products characteristic of the diazo bonds. Occasionally, the conjugated molecules may turn dark brown or even black. The diazo linkages are reversible by addition of 0.1 M sodium dithionite in 0.2 M sodium borate, pH 9.0. Upon cleavage, the color of the complex is lost. 

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