Coupling activity of diazonium

As has been mentioned previously, the reactivity of halogeno- and methylsulfonyl-l,3,4-thiadiazoles toward nucleophilic reagents is in agreement with the low electron density on the carbon atoms in the ring. The high coupling activity of the diazonium salts can be ascribed to the same cause. 

In coupling reactions of diazonium salts, nitrogen is retained and actually bonds to an activated aromatic ring in an electrophilic aromatic substitution reaction. This reaction is used to make azo dyes. 

C-coupling is of outstanding importance in the azo coupling reaction for the synthesis of azo dyes and pigments. An aromatic or heteroaromatic diazonium ion reacts with the so-called coupling component, which can be an aromatic primary, secondary, or tertiary amine, a phenol, an enol of an open-chain, aromatic, or heteroaromatic carbonyl compound, or an activated methylene compound. These reactions at an sp2-hybridized carbon atom will be discussed in Chapter 12. In the... 

Several examples of the binding of enzymes to poly(vinyl alcohol) are in the literature. These could possibly be used to treat enzyme deficiency diseases. In a recent example, trypsin was immobilized on poly(vinyl alcohol) fibers using maleic dialdehyde or bromal. While the reaction was more complete with bromal, the reaction with maleic dialdehyde gave a better support which showed decreasing activity with increasing enzyme content. The activity of the bromal activated system was independant of the enzyme content (52 ). Trypsin and papain were attached to poly(vinyl alcohol) by the reaction sequence shown in Equation 13. In this case, the crosslinked poly(vinyl alcohol) is treated by the 1,3-dioxalone derivative and then converted to either the isothiocyanate or the diazonium salt for coupling with the enzyme. The bound enzymes showed significant, altho reduced, activity in each case (53). 

B. Coupling of Diazonium Salts with Active Methylene Compounds... 

Intramolecular coupling of diazonium salts with ortho substituents bearing an active methylene grouping or its equivalent gives rise to cinnolines, which may be considered a class of cyclic azo compounds. Three name reactions are cited here for reference only. 

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,... 

An even more serious disadvantage of this technique is that it often impairs the biological activity of the modified protein. The activities of hen s egg lysozyme (EC 3.2.1.17) and alpha amylase from Aspergillus oryzae (EC 3.2.1.1) were lessened by diazo coupling of glycosides or aniline.12 Whether the decrease in activity was due to the modification of critical residues, or to the introduction of aromatic structures, is not yet clear however, enzymes subjected to the diazocoupling conditions in the absence of the diazonium salts retained their activity, implying that the reaction conditions themselves were not responsible for the loss of activity. 

Double Coupling of Diazonium Compounds. Some compounds with an activated methyl group can form symmetric formazans with strong diazo compounds by double coupling ... 

The presence of amino substituents in the 2- or 5-position activates the oxazole ring (4-aminooxazoles are unknown). Thus 2-amino-3-aryloxazoles yield the derivatives (127 X = Cl or Br) on halogenation, and nitration of 2-dimethylamino-4-phenyloxazole afforded 2-dimethylamino-5-nitro-4-(4-nitrophenyl)oxazole, the sole example of direct nitration of the oxazole ring. 5-Dialkylamino-2-phenyloxazoles react with trifluoroacetic anhydride to form the ketones (128) and they couple with arene diazonium fluoroborates the products (129) readily rearrange to 1,2,4-triazoles (130) in DMSO solution. 

In view of the many coupling reactions of conjugate bases of activated C—H compounds with diazonium and diazo species, it is not surprising that carbanions from other source can act as coupling components, too, e.g. in (35-37) lo ... 

Salts of primary aromatic amines react with nitrous acid to produce diazonium salts. The reaction is usually performed by adding a cold solution of sodium nitrite to a cold solution of the arylamine in aqueous mineral acid. The end point of the reaction is conveniently determined by the detection of excess nitrous acid with potassium iodide-starch paper. Sulfamic acid has long been used both in industry and in the laboratory to remove excess nitrous acid. It has been found to react with the more active diazo compounds. In most cases, high temperatures are avoided to prevent the formation of phenols and the decomposition of the unstable nitrous acid. An excess of mineral acid is necessary to prevent coupling between the diazonium salt and unreacted amine (cf. method 494). If the amine salt is somewhat insoluble, a fine crystalline form, which is produced by rapid crystallization from a warm aqueous solution, may be employed. ... 

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