Phenols reactions, with diazonium salts

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. 

Diazonium salts can also be used to form ethers and phenols. Reaction of diazonium salt with an alcohol generates an ether, while thermal hydrolysis of the diazonium salt yields a phenol. Figure 13-30 illustrates both formations. As seen in Figure 13-31, this process also works on substituted aromatic systems. 

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. 

Reaction with arenediazonium salts Adding a phe nol to a solution of a diazonium salt formed from a primary aromatic amine leads to formation of an azo compound The reaction is carried out at a pH such that a significant portion of the phenol is pres ent as its phenoxide ion The diazonium ion acts as an electrophile toward the strongly activated ring of the phenoxide ion... 

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). 

The synthesized CPMV-alkyne 42 was subjected to the CuAAC reaction with 38. Due to the strong fluorescence of the cycloaddition product 43 as low as 0.5 nM, it could be detected without the interference of starting materials. TMV was initially subjected to an electrophilic substitution reaction at the ortho-position of the phenol ring of tyrosine-139 residues with diazonium salts to insert the alkyne functionality, giving derivative 44 [100]. The sequential CuAAC reaction was achieved with greatest efficiency yielding compound 45, and it was found that the TMV remained intact and stable throughout the reaction. 

The azo produets obtained have an extended conjugate system having both the aromatie rings joined through the -N=N- bond. These compormds are often coloured and are used as dyes. Benzene diazonium chloride reacts with phenol in which the phenol molecule at its para position is coupled with the diazonium salt to formp-hydroxyazobenzene. This type of reaction is known as coupling reaction. Similarly the reaction of diazonium salt with anUtne yields p-aminoazobenzene. This is an example of electrophilic substitution reaction. 

Reaction of Diazonium Salts with Quinones and with Phenols.239... 

Reaction of Diazonium Salts with Quinones and with Phenols. Aryl-diazonium salts couple with quinones in the presence of sodium acetate to... 

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... 

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. 

The coupling reactions of phenols with diazonium salts take place most readily using the phenoxide anions. Many of the products are dyestuffs (see below). 

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. ... 

Through researches in aromatic chemistry it was not tong before synthetic phenol became available. Prior to work by Griess on aromatic diazo compounds published in 1860, Hunt (ref.1) had in 1849 obtained phenol from a diazonium salt produced by the reaction of aniline hydrochloride and siver nitrite. F.A. Kekule, (1829-1896), Fig.3, in 1867 (ref.2) described the recently completed sulphonation of benzene and fusion of the sulphonic acid with alkali as a new... 

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