Electrophilic aromatic substitution diazotization

The C-nitrosation of aromatic compounds is characterized by similar reaction conditions and mechanisms to those discussed earlier in this section. The reaction is normally carried out in a strongly acidic solution, and in most cases it is the nitrosyl ion which attacks the aromatic ring in the manner of an electrophilic aromatic substitution, i. e., via a a-complex as steady-state intermediate (see review by Williams, 1988, p. 58). We mention C-nitrosation here because it may interfere with diazotization of strongly basic aromatic amines if the reaction is carried out in concentrated sulfuric acid. Little information on such unwanted C-nitrosations of aromatic amines has been published (Blangey, 1938 see Sec. 2.2). 

Hydro-de-diazoniation seems to be an unnecessary reaction from the synthetic standpoint, as arenediazonium salts are obtained from the respective amines, reagents that are normally synthesized from the hydrocarbon. Some aromatic compounds, however, cannot be synthesized by straightforward electrophilic aromatic substitution examples of these are the 1,3,5-trichloro- and -tribromobenzenes (see below). These simple benzene derivatives are synthesized from aniline via halogenation, diazotization and hydro-de-diazoniation. Furthermore hydro-de-diazoniation is useful for the introduction of a hydrogen isotope in specific positions. 

Dibenzo[f,. ]cinnolines 259 have been obtained from 2-naphthylanilines 258 via diazotization followed by intramolecular electrophilic aromatic substitution (Equation 65) <2003BMC1475>. 

The second route utilizes the introduction of the chlorosulfonyl substituent directly onto the aromatic nucleus. The reaction of substituted benzenes with chlorosulfonic acid gives good yields of arylsulfonyl chlorides however, the aryl substituent dictates the position of attachment of the chlorosulfonyl function in this electrophilic aromatic substitution.7 The method described herein allows replacement of a diazotized amine function by the chlorosulfonyl group. The ready availability of substituted anilines makes this the method of choice for the preparation of arylsulfonyl chlorides. 

Aryldiazonium ions are important synthetic intermediates because they provide a means of modifying substituents already located at specific positions on the ring. The synthesis of an aryldia-zonium ion on a multiply substituted aromatic ring allows us to make compounds that sequential electrophilic aromatic substitution could not produce. For example, bromination of aniline yields tribromoanihne. Diazotization of the product followed by treatment with hypophosphorous acid removes the amino group. The three bromine groups are located meta to one another. Direct bromination of benzene would not produce this compound because bromine is an ortho-para director. 

Because of the limited range of aromatic compounds that react with diazonium ions, selectivity data comparable to those discussed for other electrophilic substitutions are not available. Because diazotization involves a weak electrophile, it would be expected to reveal high substrate and position selectivity. 

Electrophilic substitution reactions of substituted 2,1-benziso-thiazoles have already been discussed. The only other functionally substituted compound so far studied in any detail is the 3-amino derivative (87). This compound is readily diazotized and the dia-zonium salt formed (88) couples with tertiary aromatic amines yielding azo dyes.117,119-121 The salt (88) also undergoes the usual Sandmeyer reactions, and other 3-substituted derivatives, such as the cyano compound (89) may be prepared.111 Acylation of the amine (87) yields diacyl derivatives which appear to possess the 3-acylimino structure (90).111... 

Diazonium compounds, which are formed from aromatic amines with nitrous acid, may react with proteins by electrophilic substitution of the aromatic amino acid residues. Among these, bis-diazotized benzidine (BDB), o-dianisidine, benzidine-(2,2 or 3,3 )-disulphonic acid have been used extensively for protein conjugation (Kennedy et al., 1976a), but they may inactivate the enzyme or the antibody (coupling occurs mainly via the histidyl and tyrosyl residues). 

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