Diazonium coupling

A large primary isotope effect kH/kD = 3.6 had also been found earlier by Ibne-Rasa122 in the nitrosation of 2,6-dibromophenol in the 4 position which was also shown to be base-catalysed. These values are not unexpected in view of the isotope effect found with diazonium coupling which involves a similarly unreactive electrophile, so that the rate-determining transition state will be displaced well towards products. Furthermore, the intermediate will have a quinonoid structure and will, therefore, be of low energy consequently, the energy barrier for the second step of the reaction will be high. 

Conant and Peterson123 made the first kinetic study of the coupling of diazonium ions with aromatics, and measured the rates of reaction of diazotised aniline and its 2-MeO, 4-Me, 4-Br and 4-S03H derivatives with the sodium salts of 4-hydroxybenzenesulphonic acid, 2-naphthol-3,6-disulphonic acid, 1-naphthol-3,8-disulphonic acid, and l-naphthol-4-sulphonic acid. The reaction was second-order, viz. 

From a comparison of the model curves of the variation in log rate versus pH expected for reaction of possible diazonium species with possible amine and phenolic species (Figs. 1 and 2) with those obtained (Table 28) for the reaction of 

The diazonium ion is a very weak electrophile since the positive charge can be delocalised into the aromatic ring, and its reactivity is modified by substituents 

RATE COEFFICIENTS FOR REACTION OF DIAZOTISED Ar NH2 WITH ArH124 125 

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The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde 18. Formation of the oxime with hydroxylamine is followed by dehydration to the nitrile. Reaction with anhydrous methanolic hydrogen chloride leads to imino ether and addition-elimination of ammonia leads to the antidepressant amid-ine, nitrafudam (20). ... 

Diazonium coupling reactions are typical electrophilic aromatic substitutions in which the positively charged diazonium ion is the electrophile that reacts with the electron-rich, ring of a phenol or arylamine. Reaction usually occurs at the para position, although ortho reaction can take place if the para position is blocked. 

Fig. 1. Theoretical curve of pH versus log rate for diazonium coupling of amines.

Some diazonium couplings are subject to base catalysis and in these cases kinetic isotope effects are observed but since the rate of catalysed reaction is not linearly related to the base concentration (see p. 7), the SE3 mechanism is ruled out and the Se2 mechanism must operate, viz. 

Thus, diazonium coupling of 3 gave no isotope effect, while coupling of 5... 

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