Nitration and Coupling With Diazonium Salts

Both 2-pyrazolin-5-ones and 3-pyrazolin-5-ones undergo substitution at C-4 in an aromatic fashion. Halogenation, nitration and coupling with diazonium salts occur readily. In 2-pyrazolin-5-ones such reactions... 

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). 

Instead, these heterocycles and their derivatives most commonly undergo electrophilic substitution nitration, sulfonation, halogenation. Friedel-Crafts acylation, even the Reimer-Tiemann reaction and coupling with diazonium salts. Heats of combustion indicate resonance stabilization to the extent of 22-28 kcal/ mole somewhat less than the resonance energy of benzene (36 kcal/mde), but much greater than that of most conjugateci dienes (about Tlccal/mole). On the basis of these properties, pyrrole, furan, and thiophene must be considered aromatic. Clearly, formulas I, II, and III do not adequately represent the structures of these compounds. 

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 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. ... 

Perhaps the most characteristic reaction of dihydrodiazepinium salts is their electrophilic substitution at position 6. Thus they are readily deuteriated,20 26 4142 halogenated,9 15 26 35 and nitrated,28 43 44 and couple with diazonium salts.45 Reaction occurs under conditions similar to those... 

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. 

Under the influence of nitrosylsulfuric acid, 2-amino-5- and -6-bromo-l-methylben-zimidazoles (183) are converted, as a result of self-coupling, into the 2, 5- (184) and 2, 6-(185) azobenzimidazoles. Even the 5,6-dibromo analogues can react in a similar way by loss of one of the bromine atoms (Scheme 94) (72CHE1533). Coupling with diazonium salts of 4-amino- and 2-methyl-4-amino-benzimidazole occurs at C-7, while a protected 4-amino group (acetylated) directs nitration into both the 5- and 7-positions. A 4-fluoro substituent likewise leads to 7-nitration (74CRV279). 

The 2-position of the resorcinol rings may undergo substitution by mild electrophiles, such as bromination, coupling with diazonium salts and Mannich-type reactions, while more drastic reactions such as nitration or sulphonation failed. 

An X-ray structure determination of two such compounds (R=Me, Ph X=N02) located theenolic hydrogen atom symmetrically placed between the two oxygen atoms [250]. The unsubstituted compounds (X=H] readily undergo electrophilic substitution, for example nitration and bromination, at the 4-position, but couple with diazonium salts at the 3-position [20]. The difference in the latter case has been attributed to initial attack at an oxygen atom followed by a rearrangements [20]. 

Nitrates and nitrites are first reduced to nitrosyl chloride with thionyl chloride. The volatile nitrosyl chloride then reacts with 4-aminobenzenesulfonic acid to yield a diazonium salt that then couples with 8-hydroxyquinoline to form a colored azo compound. Hence, the coupling reagent is applied to the chromatogram first. 

The most representative example of this type of reaction is the so-called Griess reaction, originally developed for the kinetic determination of nitrite. Nitrite in a weakly acidic solution reacts with an amine (usually sulfanilic acid) to form the corresponding diazonium salt, which then couples with a naphthylamine or naphthol. This reaction can also be used for the kinetic determination of nitrate after reduction in a column, as well as for measuring other species such as sulfonamides (Bratton-Marshall reaction), and benzodiazepines and N-methylcarba-mate pesticides, the hydrolysis of which yields the corresponding benzophenones (which can be diazoti-zed) and naphthols (useful for the coupling reaction), respectively. 

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