Benzene derivatives with diazonium salts

There is a long history of the preparation of explosive solids or oils from interaction of diazonium salts with solutions of various sulfides and related derivatives. Such products have arisen from benzene- and toluene-diazonium salts with hydrogen, ammonium, or sodium sulfides [1,5] 2- or 3-chlorobenzene-, 4-chloro-2-methylbenzene-, 2- or 4-nitrobenzene- or 1- or 2-naphthalene-diazonium solutions with hydrogen sulfide, sodium hydrogen sulfide or sodium mono-, di- or poly-sulfides [l]-[4,7], 4-Bromobenzenediazonium solutions gave with hydrogen sulfide at -5°C a product which exploded under water at 0°C [2], and every addition of a drop of 3-chlorobenzenediazonium solution to sodium disulfide solution... 

Diazo coupling in quinazolines occurs in the benzene ring, with the normal benzene or naphthalene requirement for the presence of strongly electron-donating substituents. Perimidines couple readily in the 6(7)-position with diazonium salts to form blue azo derivatives. The reaction has been described for perimidine, 2-substituted derivatives, 6(7)-chloroperimidine, and 2-aminoperimidine <1981RCR816>. 

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. 

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 most noteworthy reaction of azo-compounds is their behaviour on reduction. Prolonged reduction first saturates the azo group, giving the hydrazo derivative (C NH-NH C), and then breaks the NH NH linkage, with the formation of two primary amine molecules. If method (1) has been employed to prepare the azo-compound, these two primary amines will therefore be respectively (a) the original amine from which the diazonium salt was prepared, and (6) the amino derivative of the amine or phenol with which the diazonium salt was coupled. For example, amino-azobenzene on complete reduction gives one equivalent of aniline, and one of p-phenylene diamine, NHaCeH NH benzene-azo-2-naphthoI similarly gives one equivalent of aniline and one of... 

In Brown s classification a diazonium ion is a reagent of very low reactivity and correspondingly high substrate selectivity and regioselectivity. This follows from the fact that benzenediazonium salts do not normally react with weakly nucleophilic benzene derivatives such as toluene. More reactive heteroaromatic diazonium ions such as substituted imidazole-2-diazonium ions will even react with benzene (see Sec. 12.5). 

When phenol is treated with one equivalent of a diazonium salt at pH 7-8 coupling occurs mainly at the 4-position of the benzene ring, but small amounts of the 2-azo and 2,4-disazo compounds are also formed [24]. With an excess of diazonium salt under neutral conditions the 2,4-disazo derivative is formed [25] and under strongly alkaline conditions the 2,4,6-... 

Coupling of a diazonium salt with another benzene derivative to form an azo compound, a compound containing a nitrogen-nitrogen double bond. 

A diazonium salt reacts with copper(I) cyanide to form a benzonitrile. Because a cyano group can be hydrolyzed to a carboxylic acid, reduced to an amine or aldehyde, or converted to a ketone with organometallic reagents, this reaction provides easy access to a wide variety of benzene derivatives using chemistry described in Section 22.18. 

Properties White crystals (yellow or pink when impure) unpleasant penetrating odor. Bp 217C, mp 42-43C, d 1.306, refr index 1.5579 (40C), flash p 250C (121C). Slightly soluble in water soluble in benzene, alcohol, and ether. Volatile with steam. A 1% solution is acid to litmus. Combustible. Derivation Chlorination of phenol, from chlorani-line through the diazonium salt. 

The dyes of this class are derived from aromatic azo compounds, such as azobenzene, CeHs—N = N—CeHs. They are prepared by treating a diazonium salt with an amine or a phenol. Thus, if a solution of m-phenylene diamine is added to a dilute solution of benzene-diazonium chloride, the hydrochloride of diamino-azobenzene, which is the dye chrysoidine, is formed —... 

Using aryl diazonium salts, it is possible to make a series of highly colored and highly important compounds known as azo dyes. In Chapter 1, the dye mauveine A (see 148) was described as one of the first commercial dyes. William Perkin (England 1838-1907) prepared 148 in 1858 from aniline, and it was shown to be valuable for the preparation of many other dyes, including fuchsine, safranine, and the indulines. Mauveine as well as other diazo compounds is produced by the reaction of a diazonium salt with a benzene derivative that has an electron-releasing substituent. 

One example is the reaction of 132 with W,iV-dimethylaniline (142) to produce diazo compound 143. The reaction works only when one benzene derivative is highly reactive (contains a powerful activating substituent) the mechanism involves attack of one benzene ring on the diazo unit of the second. Many such compounds are prepared in this manner. An example is the coupling reaction of the diazonium salt (145) derived from 4-nitroaniline (144) and the sodium salt of 2-hydroxynaphthalene (146) to give 147 (this has the common name o para red and is used as an acid-base indicator). 

Aromatic alcohols (phenols) can be prepared by treatment of a diazonium salt (ArN2 ) with water, acid, and heat. In this substitution reaction, water acts as a nucleophile and replaces the excellent nitrogen leaving group (N2) on the diazonium salt. The diazonium salt is prepared in three steps from benzene (or a substituted benzene derivative, but such compounds will be addressed in a later part of this book). First, nitration of benzene with HNO3 and H2SO4... 

The methods described above for alkyl halides (on sp hybridized carbons) cannot be applied to the synthesis of aryl halides (on sp hybridized carbons). The introduction of a halogen to benzene (or a benzene derivative) can be accomplished either by an electrophilic aromatic substitution reaction (Cy FeCls or Br2/FeBr3) or by treatment of a diazonium salt (ArNaO with a halide nucleophile (Cul, CuBr, HBF4, or KI). 

Since electrophilic aromatic substitution begins with benzene (or a benzene derivative), the retrosynthesis of an aryl chloride or bromide simply involves the replacement of the halide with a hydrogen atom. Another possible retro-synthesis that can be applied to any aryl halide is an FGI that replaces the halide with a nitro group, since the nitro group can be converted to any halide via the diazonium salt. 

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