Phenol diazo coupling

Pyrazoles and imidazoles exist partly as anions (e.g. 108 and 109) in neutral and basic solution. Under these conditions they react with electrophilic reagents almost as readily as phenol, undergoing diazo coupling, nitrosation and Mannich reactions (note the increased reactivity of pyrrole anions over the neutral pyrrole species). 

The general discussion (Section 4.02.1.4.1) on reactivity and orientation in azoles should be consulted as some of the conclusions reported therein are germane to this discussion. Pyrazole is less reactive towards electrophiles than pyrrole. As a neutral molecule it reacts as readily as benzene and, as an anion, as readily as phenol (diazo coupling, nitrosation, etc.). Pyrazole cations, formed in strong acidic media, show a pronounced deactivation (nitration, sulfonation, Friedel-Crafts reactions, etc.). For the same reasons quaternary pyrazolium salts normally do not react with electrophiles. 

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). 

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 azo-dyes derived from phenols are called acid dyes, those derived from amines basic dyes. But since, in industry, the starting materials, not only diazo-components (diazotised amines), but also azocomponents (coupled phenols or amines), are nearly always sulphonic acids, this distinction is pointless. The vast majority of the azo-dyes... 

Reactions of the ligand which are so retarded by coordination that the rate constants are very different for the free and the complexed species. Diazo coupling of aromatic phenolates falls into this class. 

Because of the small concentration of the 2 1 complex the last term can be ignored. From the extreme rate values in the absence of zinc and with an excess of zinc, 2i and 22 are determined as 2.4 X 104 min.-1 and 1.57 min.-1 respectively. These values can be combined with the trend in the rate constants to give the stability constant of the reactive complex, presumably Zn(OR)(OAc), as 3 X 107. For the simple zinc complex in water the literature values of the stability constant for the 1 1 complex vary from 2.5 X 108 to 6.3 X 108. The diazo coupling reaction of the complex indicates the smaller effect of coordination vis a vis protonation since this reaction is very sensitive to such effects and does not proceed with phenols. Unfortunately the choice of cations for such a reaction is restricted since the cation should not interfere with the analytical methods used to obtain the kinetic data nor should it introduce additional reactions such as occur with transition metal cations which can catalyze the decomposition of the diazonium salt via a redox process. 

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). 

Diazo coupling often takes place in basic solutions because deprotonation of the phenolic —OH groups and the sulfonic acid and carboxylic acid groups helps to activate the aromatic rings toward electrophilic aromatic substitution. Many of the common azo dyes have one or more sulfonate (—SO3) or carboxylate (—COO-) groups on the molecule to promote solubility in water and to help bind the dye to the polar surfaces of common fibers such as cotton and wool. 

Give examples using arenediazonium salts in diazo coupling reactions and in the synthesis of phenols and aryl chlorides, bromides, iodides, fluorides, and nitriles. 

Pyridines, pyridones, and pyrones containing an amino or hydroxy group also undergo diazo coupling, nitrosation, and Mannich reactions, as do their benzenoid analogues, phenol or aniline. Such reactions take place under conditions of relatively low acidity where less of the compound is in the form of an unreactive cation. 

The masking of aromatic phenols against the oxidative side reactions possible in a medium used to effect diazo coupling can be achieved via coordination. For example, the reaction of 4-diazodimethylaniline with... 

C-Nitroso compounds. As an alternative to diazo coupling and reduction, a phenol is often converted into the o- or p-nitroso derivative and this is reduced, as exemplified by Sherman and Taylor s synthesis of diaminouracil." The rose red... 

The erroneous statement that these two new bases were phenolic was based upon a diazo-coupling reaction during which other changes must occur (Findlay and Small, J.A.C.8., 1951, 73, 4001). Acetolysis of [B] yields 3-methoxy-4 6-diacetoxyphenanthrene. 

The most sensitive and reproducible manual procedure in the latter group, in which the diazo coupling reaction is utilized, is that of Fishman et al. (F14, S48). In this method, the liberated phenol from phenyl phosphate is coupled with 5-nitroanisole-2-diazoniumnaphthalene-l,5-di-sulfonate (Fast Red B salt, Hilton-Davis Chemical Co., Cincinnati, Ohio) (Fig. 2). 

The tissue preparations were diluted (1 12) in heat-inactivated sera (1 hour at 55°C), and incubated in 0.02 M Veronal buffer (pH 9.8) containing 0.018 M disodium phenyl phosphate for 2 hours at 37°C. Phenol was measured via a diazo coupling procedure. Conditions for heat-inactivating the tissue enzymes were 16 minutes at 55°C. By subtracting from the total activity the intestinal component, which is measured by n-phenylalanine sensitivity, one obtains the sum of the activities of liver and bone. The ratio of the two was computed from the heat inactivation minus that attributed to intestine, employing 91.2% heat inactivation to represent 100% bone and 51.4% heat inactivation indicating all liver. In this way one arrives at values for bone, liver, and intestinal alkaline phosphatase. 

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