19.30: Aryldiazonium Salts to Azo Dyes: Diazo Coupling
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the para position. However, if the para position is substituted, the coupling occurs instead at the ortho position.
Figure 1. The generic representation of a diazo coupling reaction. The diazonium compound is on the far left, and the product is an azo compound. H–Ar′ must be an activated compound.
Mechanistically, the reaction proceeds via an electrophilic substitution reaction via donation of the π electrons of the activated aromatic nucleus to the electrophilic nitrogen, resulting in a resonance-stabilized carbocation.
Figure 2. The mechanism of diazo coupling and the resonance stabilization of the carbocation (where ERG = OH and Ar = Ph).
Figure 3 depicts the final step, which involves the deprotonation of the carbocation to yield the diazo product.
Figure 3. The formation of a diazo compound.
As depicted in Figure 4, the role of basicity in diazo coupling reaction is evident. For phenols, it is most feasible under slightly alkaline conditions, where the phenol is present as phenoxide ions. The formation of appreciable phenoxide ions activates the aromatic ring, thereby enhancing the coupling between arenediazonium ions and phenols in a slightly basic solution. However, excess alkalinity of the solution (pH > 10) leads to the formation of diazohydroxide or diazotate ions, which are unreactive towards coupling.
Figure 4. The influence of basicity on the diazo coupling reaction.
Unlike phenols, as shown in Figure 5, the diazo coupling of amines occurs optimally in the acidic pH range of 5–7. The reaction is driven by the concentration of the arenediazonium ion, which is at a maximum at this pH.
Figure 5. The diazo coupling reaction of amines.
Diazo-coupled compounds feature an extended conjugated π electron system by aligning the two aromatic rings in conjugation, making them strongly chromophoric. This results in the intense color of the azo compounds known as azo dyes. Examples of azo dyes include alizarin yellow, butter yellow, congo red, orange II, and para red.
Apart from being an excellent dye, diazo compounds were also identified as antibiotics when Domagk G., in 1935, successfully used prontosil on his daughter to prevent lethal streptococcal infection, which marked the beginning of the modern era of synthetic antibiotics. Prontosil is inactive against bacteria, but in the human body, it metabolizes to give a compound called sulfanilamide, which exhibits antibacterial properties.
Figure 6. The metabolism of prontosil to the active drug form of sulfanilamide.
