Phenols coupling with diazonium salts

Naphthols undergo the usual reactions of phenols. Coupling with diazonium salts is particularly important in dye manufacture (see Sec. 23.17) the orientation of this substitution is discussed in the following section. 

Other typical electrophilic aromatic substitution reactions—nitration (second entr-y), sul-fonation (fourth entry), and Friedel-Crafts alkylation and acylation (fifth and sixth entries)—take place readily and are synthetically useful. Phenols also undergo electrophilic substitution reactions that are limited to only the most active aromatic compounds these include nitrosation (third entry) and coupling with diazonium salts (seventh entry). 

As already mentioned, hydroxypyrazines exist in tautomeric equilibria with the corresponding pyrazinones which are normally the predominant species in the equilibria. Some of the reactions of hydroxypyrazines are reminiscent of those of phenols they can, for example, be coupled with diazonium salts and brominated and nitrated in either the ortho or para position to the hydroxyl group. Coupling with diazonium salts occurs in neutral or weakly alkaline solution, but if the reaction is carried out in 1 M sodium hydroxide solution, arylation of the pyrazine ring takes place. From hydroxy-pyrazine and benzenediazonium chloride 47% 2-hydroxy-3-phenyl-and 4% 2-hydroxy-3,6-diphenylpyrazine are obtained. 

Nitrogen s extra pair of electrons, which is responsible for the usual basicity of nitrogen compounds, is involved in the tt cloud, and is not available for sharing with acids. In contrast to most amines, therefore, pyrrole is an extremely weak base (ATj, -- 2.5 X 10 14). By the same token, there is a high electron density in the ring, which causes pyrrole to be extremely reactive toward electrophilic substitution it undergoes reactions like nitrosation and coupling with diazonium salts which are characteristic of only the most reactive benzene derivatives, phenols and amines. 

Like other aromatic compounds, these five-membered heterocycles undergJ nitration, halogenation, sulfonation, and Friedel-Crafts acylation. They are mucji more reactive than benzene, and resemble the most reactive benzene derivatives (amines and phenols) in undergoing such reactions as the Reimer-Tiemann reaction, nitrosation, and coupling with diazonium salts. 

The early work on this compound was confused by Pschorr s failure to recognize its phenolic nature. He noted the alkali-soluble nature of the methiodide and the production of a mono-acetyl derivative, but concluded, on account of the apparent insolubility of the parent base in alkali, that fission of the cyclic ether fink occurred during the reactions of the base with acetic anhydride and methyl iodide [7]. That /3-ethylthiocodide is indeed a phenol was demonstrated by Morris and Small [3] it gives coloured solutions with alcoholic ferric chloride and readily couples with diazonium salts in alkaline solution to give red dyes moreover it is soluble in alkali, though not readily so, being a very weakly acidic phenol. 

Phenol readily couples with diazonium salts to yield coloured compounds. The latter can be nsed for the photometric detection of phenol as in the case of diazotized 4-nitroaniline. Sahcylic acid (2-hydroxybenzoic acid) can be prodnced by the Kolbe-Schmitt reaction (stndied by the density functional method ) from sodinm phenolate and carbon dioxide, whereas potassium phenolate gives the para compound. Alkylation and acylation of phenol can be carried out with aluminium chloride as catalyst methyl groups can also be introduced by the Mannich reaction. Diaryl ethers can only be produced under extreme conditions. 

The fact that the one-pot synthesis of caUxarenes works best with p-f-butylphenoP was beneficial for the whole area, since the f-butyl groups are easUy removed by trans-butylation with AICI3 in toluene (as solvent and acceptor), converting calixarenes 2a-e into the p-unsubstituted calixarenes 2na-e. Thus, the p-positions at the wide rim are available for virtually all kinds of electrophilic substitution reactions which are possible with phenols . Sulphonation, nitration, bromination (or iodination), bromomethyla-tion, aminomethylation, formylation, acylation and coupling with diazonium salts are examples. 

Examples of the selective substitution of phenol units in partially O-alkylated (or 0-acylated) calixarenes (reaction c)) are the bromination , iodination, nitration , formylation , chloromethylation , alkylation and coupling with diazonium salts. ... 

Pyridones and pyrazolones, tautomers of the hydroxypyridines and hydroxypyrazoles, respectively, are phenol-like in behaviour and are sufficiently activated to couple with diazonium salts, giving commercially valuable azo dyes. 

Coupling reactions with diazonium salts to yield intensely colored azo derivatives have often been used for the detection of phenols, primary aromatic amines and electron-rich heterocyclics. 

Equally popular are azo couplings of diazonium salts that keep the nitrogen atoms in the product. The solid-solid version is very suitable with appropriate phenols such as 296 and 299. The waste-free and quantitatively obtained azo dye salts can be neutralized. The free dyes have the hydrazono structure (297, 298) or the azo structure (300) [99-100] (Scheme 45). The prescription should be carefully followed for safety reasons ... 

Perhaps the best-known method of preparing aromatic azo compounds involves the coupling of diazonium salts with sufficiently reactive aromatic compounds such as phenols, aromatic amines, phenyl ethers, the related naphthalene compounds, and even sufficiently reactive aromatic hydrocarbons. Generally, the coupling must be carried out in media which are neutral or slightly basic or which are buffered in the appropriate pH range. The reaction may also be carried out in nonaqueous media. While some primary and secondary aromatic amines initially form an A-azoamine, which may rearrange to the more usual amino-C-azo compound, tertiary amines couple in a normal manner. 

Generally the coupling of diazonium salt is carried out under neutral to slightly alkaline conditions. In coupling with amines or phenols, it has been demonstrated that the active species are the diazonium cation, the free amine,... 

Aryldiazonium salts are weak electrophiles. Consequently, they undergo Ar-SE reactions via sigma complexes (azo couplings) only with the most strongly activated aromatic compounds. Only phenolates and secondary and tertiary aromatic amines react with them. Primary aromatic amines react with diazonium salts, too, but via their N atom. Thus, triazenes, that is, compounds with the structure Ar—N=N—NH—Ar are produced. Phenol ethers or nonde-protonated phenols can react with aryldiazonium salts only when the latter are especially good... 

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