Diazo coupling with

The diazo coupling with C—H acidic aliphatic substrates is a feature of the Japp-Klingemann reaction. 

Nitrite is determined by diazo-coupling with sulfanilamide and NEDA (see below for full name), forming a reddish color that can be determined with a visible spectrophotometer. 

Ellwood et al.235,236 have patented and published236 information concerning diazo coupling with heterocyclic compounds whose rates were enhanced by the use of alkylaryl sulfonates (160) as PT catalysts. 

Arylcopper compounds decompose alkyldiazo compounds [Eq. (34)] 34, 37, 255). for which pentafluorophenylcopper is a very active catalyst. Bis(trifluoromethyl)diazomethane and pentafluorophenylcopper give perfluoro-2-phenylpropene under mild conditions, perhaps via elimination of copper(I) fluoride from an intermediate copper compound 37). Benzenediazonium compounds react in one of two ways 37) (1) diazo coupling with ffi-trifluoromethylphenylcopper to give m-trifluoromethyl-azobenzene in 93% yield or (2) direct displacement with pentafluorophenylcopper to give a 16% yield of 2,3,4,5,6-pentafluorobiphenyl, as well as 75% decafluorobiphenyl and 65% azobenzene. 

The autoxidation of hydroxylamine to nitrite also involves a radical chain process (Kono, 1978), and the reaction is carried out at high pH. The assay was originally utilized by Elstner and Heupel (1976) who initiated the autoxidation by O2 generated by the xanthine/xanthine oxidase reaction. Nitrite formation was determined colorimetrically at 530 nm by diazo coupling with a-naphthylamine and superoxide dismutase was found to inhibit end product formation. Kono (1978) developed the assay further by utilizing nitroblue tetrazolium as the... 

Nitration can be effected by nitric acid alone or by using nitric acid-sulfuric acid mixtures and it is the position and nature of substituents in the ring that influence the strength of the reagent needed. The diazepinium salts can be brominated using either bromine in methanol or V-bromo-succinimide JV-chloro- and JV-iodosuccinimide furnish the 6-chloro and 6-iodo derivatives, respectively. The diazepinium salts undergo diazo coupling with aryldiazonium salts but the products are readily hydrolyzed. 

The formation of the l,6a-dithia-5,6-diazapentalene (30) by attempted diazo-coupling with 2-t-butyl-6a-thiathiophthen has been mentioned earlier in this chapter. 5,6-Diaza-compounds have also been obtained from dithiolylidene aldehydes and from l,6a-dithia-6-azapentalenes, suggesting that the N-6—S-6a bond must be relatively strong, like the 0-1—S-6a bond in l-oxa-6,6a-dithia-2-azapentalenes. Members of the l,6a-dithia-5,6-diaza series can also be obtained by the reaction of 3-methyl-1,2-dithiolium salts with p-nitrobenzenediazonium fluoroborate in ethanol. Coupling of diazonium salts with l,6-dioxa-6a-thiapentalene (61 R = H) leads to yet another new system (65). 

The most important reaction of the diazonium salts is the condensation with phenols or aromatic amines to form the intensely coloured azo compounds. The phenol or amine is called the secondary component, and the process of coupling with a diazonium salt is the basis of manufacture of all the azo dyestuffs. The entering azo group goes into the p-position of the benzene ring if this is free, otherwise it takes up the o-position, e.g. diazotized aniline coupled with phenol gives benzeneazophenol. When only half a molecular proportion of nitrous acid is used in the diazotization of an aromatic amine a diazo-amino compound is formed. 

Basic, forms a stable water-soluble dihydrochloride. Diazotization gives brown azodyes (Bismarck brown) owing to the coupling of the partially diazotized base with the excess of diamine. Is also used as an end component of many azo-dyes, readily coupling with one or two molecules of diazo compound. 

Diazo coupling involves the N exocyclic atom of the diazonium salt, which acts as an electrophilic center. The diazonium salts of thiazoles couple with a-naphthol (605). 2-nitroresorcinol (606), pyrocatechol (607-609), 2.6-dihydroxy 4-methyl-5-cyanopyridine (610). and other heteroaromatic compounds (404. 611) (Scheme 188). The rates of coupling between 2-diazothicizolium salts and 2-naphthol-3.6-disulfonic acid were measured spectrophotometrically and found to be slower than that of 2-diazopyridinium salts but faster than that of benzene diazonium salts (561 i. The bis-diazonium salt of bis(2-amino-4-methylthiazole) couples with /3-naphthol to give 333 (Scheme 189) (612). The products obtained from the diazo coupling are usuallv highly colored (234. 338. 339. 613-616). 

Diazo Coupling Reactions. Alkylphenols undergo a coupling reaction with dia2onium salts which is the basis for the preparation of a class of uv light stabilizers for polymers. The interaction of orxv i -nitrobenzenediazonium chloride with 2,4-di-/ r2 -butylphenol results in an azo-coupled product (30). Reduction of the nitro group followed by m situ cyclization affords the benzottiazole (31) (19). 

The Fuji CopiArt monochrome proofing system is based on the photogeneration of color from leuco dyes or diazo-coupling (35). CopiArt includes both positive and negative working systems (Fig. 6). For the positive working system, a diazo compound (6) reacts with a coupler (7) as shown. 

Nitrite can be deterrnined by reaction with sulfanilamide to form the diazo compound, which couples with /V-(1-naphthyl)ethylenediamine dihydrochloride to form an intensely colored red azo dye. Nitrate can be deterrnined in a similar manner after reduction to nitrite. Suitable reducing agents are cadmium filings or hydrazine. This method is useful at a nitrogen concentration of 10 -lO " M. 

Diazo coupling follows the rules of orientation of substituents in aromatic systems in accordance with the mechanism of electrophilic aromatic substitution and the concept of resonance. 

The ratio between the isomers obtained in coupling with 1,3- and 1,5-naphtholsulfonic acids depends on the reactivity of the diazo component. Energetic ones, such as the 2,4-dinitrobenzenediazonium compound, essentially couple only with l-naphthol-3-sulfonic acid [3771-14-0] in the para position, but 4-chloro-benzenediazonium salt (a weaker diazo) attacks the ortho position. Both isomers result when mononitrobenzenediazonium compounds are used. The tendency to couple para is greater in l-naphthol-5-sulfonic acid [117-59-9] C QHgO S (21). For the combination of... 

Nitro-l-diazo-2-naphthol-4-sulfonic acid prefers the 2-position in spite of the nitro group, and increasing alkalinity favors ortho coupling with diazophenols. 1-Naphthalenesulfamic acid [24344-19-2] (ArNHSO H) and N-nitro-1-naphthylamine [4323-69-7] (ArNHNO ) couple exclusively in the para position. The substitution of resorcinol [108-46-3] and y -phenylenediamine [108-45-2] is compHcated and has been discussed (29,30). The first azo dyes from aniline, eg. Aniline Yellow [60-09-3] (19) (Cl Solvent Yellow 1 Cl 11000) were manufactured in 1861 and Bismark Brown [10114-58-6] (20) (Cl Basic Brown 1 Cl 21000) appeared in 1863. The reaction is as follows ... 

Naphthol AS Coupling Components. Naphthol AS components are the aryhdes of either o-hydroxyarylcarboxycHc acids or acylacetic acids. They are free of sulfo and carboxyl groups, but form salts with bases these salts dissolve in water to give colloidal solutions, which couple with diazo components to form colored pigments. The whole class derives from the anilide of 3-hydroxy-2-naphthoic acid [92-70-6] Naphthol AS (85) (Cl Azoic Coupling Component 2). 

Furan undergoes phenylation rather than diazo coupling on reaction with ben-zenediazonium salts, and thiophene similarly yields 2- or 2,5-diaryl derivatives rather than coupled products. However, 2,5-dimethylfuran and 2-/-butylfuran give coupled products with 2,4-dinitrobenzenediazonium ion (Scheme 26). 

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). 

Diazo coupling is expected to occur only with highly reactive systems, and experiment bears this out. Diazonium ions couple with the anions of N-unsubstituted imidazoles at the 2-position (e.g. 125 yields 126) and with indazoles (127) in the 3-position. In general, other azoles react only when they contain an amino, hydroxyl, or potential hydroxyl group, e.g. the 4-hydroxypyrazole (128), the triazolinone (129) and the thiazolidinedione (130) (all these reactions occur on the corresponding anions). 

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. 

The reaction is very common in pyrazolone chemistry. Since alkoxypyrazoles and tautomerizable pyrazolones undergo this reaction and 3-pyrazolin-5-ones, like antipyrine, do not, it is assumed that the reaction takes place at C-4 of the OH tautomer. Pyrazolone diazo coupling is an important industrial reaction since the resulting azo derivatives are used as dyestuffs. For instance, tartrazine (Section 4.04.4.1.3) has been prepared this way. 3,5-Pyrazolidinediones react with aryldiazonium salts resulting in the introduction of a 4-arylazo group. As has been described in Section 4.04.2.1.4(v), diazonium salts couple in the 3-position with indazole to give azo compounds. 

The behaviour of pyrazoles towards nitrosation is similar to their behaviour described above towards diazo coupling, i.e. aminopyrazoles and pyrazolones readily react with nitrosation agents, like alkyl nitrites (81FES1019), to afford stable nitroso derivatives. Some simple nitrosopyrazoles have been isolated, for example the blue-green 3,5-dimethyl-4-nitrosopyrazole, and many others have been proposed as reactive intermediates in the direct conversion of pyrazoles into diazonium or diazo derivatives (Scheme 25) (B-76MI40402). 

Indolizine, hydroxy-conformations, 4, 451 GLC retention times, 4, 451 synthesis, 4, 121 tautomerism, 4, 198, 452 Indolizine, 2-hydroxy-synthesis, 4, 463 Indolizine, 8-hydroxy-conformation, 4, 452 Indolizine, 2-hydroxymethyl-synthesis, 4, 461 Indolizine, 3-hydroxymethyl-synthesis, 4, 461 Indolizine, 6-hydroxymethyl-synthesis, 4, 461 Indolizine, methyl-mass spectra, 4, 187, 450 NM 4, 448 Indolizine, 2-methyl-diazo coupling, 4, 454 mass spectra, 2, 529, 4, 450 nitration, 4, 50, 454 nitrosation, 4, 454 reaction with diaryl disulfide, 4, 460 reaction with nitroethane, 4, 460 Indolizine, 3-methyl-basicity, 4, 454 Indolizine, 5-methyl-acidity, 4, 461 synthesis, 4, 466 Indolizine, 6-methyl-mass spectra, 4, 450 Indolizine, l-methyl-2-phenyl-nitration, 4, 454 nitrosation, 4, 454, 455 Indolizine, 3-methyl-2-phenyl-reaction... 

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