Coupling, azo

The term, azo coupling denotes all reactions of diazonium cations with anionic substances that lead to neutral molecules with removal of the charges on the reactants 315 

Holzach, Die aromatischen Diazoverbindungen, Ferdinand Enke, Stuttgart, 1947 K. H. Saunders, The Aromatic Diazo-Compounds and their Technical Applications, Edward Arnold Co, London, 2nd ed, 1949 H. Zollinger, Chemie der Azofarbstoffe, Birkhauser Verlag, Basle and Stuttgart, 1958. 

Strictly speaking, therefore, it covers also the well-known rearrangement of diazonium salts to diazoates, e.g., the formation of diazocyanides from diazo-nium cyanides.316 According to the element with which the terminal nitrogen atom forms a new covalent bond in the coupling process, the product is called a C-, O-, N-, or S-azo compound. This Section is concerned only with C-azo compounds. 

The diazo components used for coupling are almost exclusively diazonium salts. Because their instability usually precludes the use of energetic reaction conditions such as high temperatures, and because their electrophilicity is relatively low, C-azo coupling demands particularly reactive anionic components, e.g., compounds containing active methylene groups, phenols, or aromatic amines. 

Raab in Ullmann s Enzyklopadie der Technischen Chemie, Urban Schwar-zenberg, Munich-Berlin, 3rd ed, 1953, Vol. 4, pp. 76fF. 

The experimental factor that requires most careful control in azo 

A reaction of aryl diazonium salts that does not involve loss of nitrogen takes place when they react with phenols and arylamines. Aryl diazonium ions are relatively weak electrophiles but have sufficient reactivity to attack strongly activated aromatic rings. The reaction is known as azo coupling two aryl groups are joined together by an azo (—N=N—) function. 

The product of this reaction, as with many azo couplings, is highly colored. It is called methyl red and was a familiar acid-base indicator before the days of pH meters. It is red in solutions of pH 4 and below, yellow above pH 6. 

Soon after azo coupling was discovered in the mid-nineteenth century, the reaction received major attention as a method for preparing dyes. Azo dyes first became commercially available in the 1870s and remain widely used, with more than 50% of the synthetic dye market. Chrysoidine, an azo dye for silk, cotton, and wool, first came on the market in 1876 and remains in use today. 

What amine and what diazonium salt would you use to prepare chrysoidine  

Dyes are regulated in the United States by the Food and Drug Administration (FDA). Over the years FDA has removed a number of dyes formerly approved for use in food and cosmetics because of concerns about toxicity, cancer-causing potential, or because they are skin irritants. Naturally occurring pigments, too 

PROBLEM 22.20 Cumene (isopropylbenzene) is a relatively inexpensive commercially available starting material. Show how you could prepare m-isopropyl-nitrobenzene from cumene. 

The value of diazonium salts in synthetic organic chemistry rests on two main points. Through the use of diazonium salt chemistry  

Substituents that are otherwise accessible only with difficulty, such as fluoro, iodo, cyano, and hydroxyl, may be introduced onto a benzene ring. 

Compounds that have substitution patterns not directly available by electrophilic aromatic substitution can be prepared. 

The first of these two features is readily apparent and is illustrated by Problems 22.17 to 22.19. If you have not done these problems yet, you are strongly encouraged to attempt them now. 

The second point is somewhat less obvious but is illustrated by the synthesis of 1,3,5-tribromobenzene. This particular substitution pattern cannot be obtained by direct bromination of benzene because bromine is an ortho, para director. Instead, advantage is taken of the powerful activating and ortho, para-directing effects of the amino group in aniline. Bromination of aniline yields 2,4,6-tribromoaniline in quantitative yield. Diazoti-zation of the resulting 2,4,6-tribromoaniline and reduction of the diazonium salt gives the desired 1,3,5-tribromobenzene. 

SCHEME 2.172 Synthesis of pyrrole-2-carboxylic acid from 2-trifluoroacetylpyrroles. 

4-MeOCeH4,2-furyl, 2-thienyl R = H, R -R Ar = Ph, 4-EtOCgH4,4-O2NC6H4,4-BrC6H4,4-N2C6H4C6H5 

SCHEME 2.173 Azo-coupling of N-vinylpyrroles with aryldiazonium hydrocarbonates. 

The expected oxidation of the pyrrole cycle, C=C and N=N double bonds, is not observed. The reason is a deep electron density transfer from the N-vinyl fragment to the azo group that decreases susceptibility of the vinyl group and pyrrole ring toward oxidizers. The fact that the stability of the molecule is ensured by the arylazo substituent is confirmed by deep oxidation of 2,3-dimethyl-N-vinylpyrrole in these conditions (NMR spectra of the products show no signals of the vinyl group and pyrrole ring). 

This reaction is the first example of easy selective oxidation of the methyl substituent in the pyrrole ring to hydroxymethyl and aldehyde functions. It may be considered as the simple atom-economic synthesis of phenylazopyrrole dyes bearing hydroxymethyl or aldehyde moieties. 

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Azo coupling (Section 22 18) Formation of a compound of the type ArN=NAr by reaction of an aryl diazonium salt with an arene The arene must be strongly activated toward... 

Coupling(azo) Coupling constant Coupling solvents Couplingsugar CoveUite... 

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