Diazonium salts, coupling with aromatic compounds

Diazonium salts couple readily with aromatic primary amines, giving diazoamino compounds. If for instance an aqueous solution of aniline sulphate is diazotised with a deficiency of nitrous acid, only part of it is converted into benzenediazonium sulphate and the latter then couples with the unchanged aniline to give diazoaminobenzene. The reaction is carried out at the opti-CeHsNHj.HjSO + HONO = CbHsNjHSO, + zHaO... 

There are apparent exceptions to the rule that aromatic compounds are azo coupling components only if they contain a hydroxy or an amino group. A long time ago Meyer and Tochtermann (1921) demonstrated that the 2,4,6-trinitrobenzenedi-azonium salt couples with mesitylene, isodurene (1,2,3,5-tetramethylbenzene), and pentamethylbenzene (see also Smith and Paden, 1934). That result was surprising at the time, but today it is, of course, understandable the diazonium salt used is pro-... 

Diazonium salts react with various nucleophiles in water (Eq. 11.62).106 In acidic aqueous solution, p-pheny I e ncbis di azo ni um ion reacts with alcohols more rapidly than it does with water.107 In the presence of nucelophiles such as halides, the substitution products are obtained. Furthermore, diazonium salts of aromatic compounds are excellent substrates for palladium-catalyzed coupling reactions such as the Heck-type reactions in water. 

A. Coupling of Diazonium Salts with Aromatic Compounds. 291... 

Diazotization of 3-aminoisothiazolo[4,3-c]pyridine (197) with HONO gave the 3-diazonium salt (198) in good yield. Compound (198) was coupled with aromatic amines to give the diazo dyes (199) (Scheme 17) <80BRP2074565>. 

Under the proper conditions, diazonium salts react with certain aromatic compounds to yield products of the general formula Ar—N==N—Ar, called azo compounds. In this reaction, known as coupling, the nitrogen of the diazonium group is retained in the product, in contrast to the replacement reactions we have studied up to this point, in which nitrogen is lost. 

A related process that involves diazonium salts is the Pschorr reaction, hich also couples aryl diazo-nium compounds to other aromatic rings. This diazonium salt coupling can he done under acidic conditions, but addition of copper powder usually promotes the radical process. Aryl amines generate aryl diazonium salts upon treatment with nitrous acid.l An example is the reaction of 233 to give an aryl diazonium salt, which cyclized in the presence of copper to give thaliporphine (234) in 43% yield. Kupchan called this transformation an improved Pschorr reaction. 68... 

Methylquinoxaline derivative 266 reacted with bromine to yield bromomethylquinoxaline 267 and then reacted with NaCN to yield cyanomethylquinoxaline 268. The latter readily coupled with aromatic diazonium salts to yield hydrazone derivative 269 that then reacted with active methylene reagents to yield the corresponding quinoxaUnylpyrida-zine 270. Quinoxaline 266 also reacted with DMFDMA to yield the enamine 271 that then coupled with a diazonium salt to yield aldehydehydrazone 272. Subsequently, 272 with active methylene compounds yielded the corresponding pyridazines 273 (2006M1901 Scheme 48). 

Diazonium salts react with other aromatic compounds (such as phenol) to form dyes this is known as a coupling reaction. Diazonium dyes are commercially important. 

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. 

When an aqueous solution of a diazonium salt is added to an alkaline solution of a phenol, coupling occurs with formation of an azo-compound (p. 188). If ho vc cr the ntiueous solution of the diazonium salt, t. . ., />-bromohenzene diazonium chloride, is mixed with an excess of an aromatic hydrocarbon, and aqueous sodium hydroxide then added to the vigorously stirred mixture, the diazotate which is formed, e.g., BrC,H N OH, dissolves in the hydrocarbon and there undergoes decomposition with the formation of nitrogen and two free radicals. The aryl free radical then reacts with the hydrocarbon to give a... 

Synthesis. Almost without exception, azo dyes ate made by diazotization of a primary aromatic amine followed by coupling of the resultant diazonium salt with an electron-rich nucleophile. The diazotization reaction is carried out by treating the primary aromatic amine with nitrous acid, normally generated in situ with hydrochloric acid and sodium nitrite. The nitrous acid nitrosates the amine to generate the N-nitroso compound, which tautomerizes to the diazo hydroxide. 

A diazonium salt is a weak electrophile, and thus reacts only with highly electron-rich species such as amino and hydroxy compounds. Even hydroxy compounds must be ionized for reaction to occur. Consequendy, hydroxy compounds such as phenols and naphthols are coupled in an alkaline medium (pH > of phenol or naphthol typically pH 7—11), whereas aromatic amines such as N,N diaLkylamines are coupled in a slightly acid medium, typically pH 1—5. This provides optimum stabiUty for the dia2onium salt (stable in acid) without deactivating the nucleophile (protonation of the amine). 

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). 

Arylamines are converted by diazotization with nitrous acid into arenediazonium salts, ArN2+ X-. The diazonio group can then be replaced by many other substituents in the Sandmeyer reaction to give a wide variety of substituted aromatic compounds. Aryl chlorides, bromides, iodides, and nitriles can be prepared from arenediazonium salts, as can arenes and phenols. In addition to their reactivity toward substitution reactions, diazonium salts undergo coupling with phenols and arylamines to give brightly colored azo dyes. 

Azo coupling of diazonium salts with aromatic (or pseudoaromatic) hydrocarbons is possible if the coupling agent is highly substituted. For example, azo compounds have been produced from pentamethylbenzene [12], benzpyrene [13], and azulene [1-4]. 

Since A,A -disubstituted hydrazines are readily available from a variety of sources (see Volume I, Chapter 14), their dehydrogenation constitutes a widely applicable route to both aliphatic and aromatic azo compounds. Such oxidative procedures are of particular value in the aliphatic series because so many of the procedures applicable to aromatic compounds, such as the coupling with diazonium salts, have no counterpart. The oxidation reactions permit the formation not only of azoalkanes, but also of a host of azo compounds containing other functional groups, e.g., a-carbonyl azo compounds [83], a-nitrile azo compounds [84], azo derivatives of phosphoric acid [85], phenyl-phosphoric acid derivatives [86],... 

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. 

The coupling of aromatic diazonium salts with a variety of aromatic compounds is the basis of the azo dye industry [2-5]. A variety of dying techniques are available but, fundamentally, two procedures are involved ... 

Azo dyes, characterized by the presence of one or more azo groups (-N=N-), are the most commercially important class of dyes. These compounds are synthesized using a diazoti-zation reaction in which a primary aromatic amine reacts with nitrous acid to form a diaz-onium salt. The diazonium compound then typically is coupled with phenols, napthols, aromatic amines, heterocycles, or a variety of other compounds containing active methylene groups. Azo dyes are used in acid, direct, disperse, fiber reactive, and mordant applications. 

Coupling Components With Condensed Cyclic Ammo nium Residues. Heterocyclic compounds in which the condensed benzene ring is substituted by a hydroxyl or an amino group can be coupled with diazonium compounds and may also be quatemized, either prior or subsequent to the coupling reaction, to yield cationic azo dyes. l,2-Dialkyl-6-nitroindazolium salts are reduced to the 6-amino compounds and then coupled with diazonium salts of aromatic amines. These dyes (e g., 21) color polyacrylonitrile in bright yellow to orange shades [64],... 

The 4-aminopyridine derivative 92, prepared from the reaction of ethyl benzoylacetate and malononitrile dimer 91, undergoes the coupling reaction with aromatic diazonium salts to afford azo derivatives such as 93. Under refluxing conditions in ethanolic sodium hydroxide, these azo compounds cyclize to pyrido[3,2-f]pyridazines and pyrido[3,2-r]-pyridazino[2, 3 - ]quinazolines (Scheme 15) <2005AP329>. 

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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