Aromatic nitration coupling reaction

The examples that are treated below are those sequences where all steps - except the last — are preparations for a color or fluorescence derivatization reaction which is carried out in the last step, i. e. they can be regarded as a sort of selective in situ pretreatment for a final detection reaction. Such reaction sequences are frequently necessary because all the reagents cannot be mixed together in a single solvent, or because it is necessary to dry, heat or irradiate with UV light between the individual reaction steps. The detection of aromatics by the reaction sequence nitration — reduction — diazotization - couple to form an azo dye is an example of this type (Fig 21). 

ArNHj remains (as it is a weak base), but the concentration is low enough to prevent as yet undiazotised amine undergoing a coupling reaction with the first formed ArNj p. 147). Aromatic diazonium chlorides, sulphates, nitrates, etc., are reasonably stable in aqueous solution at room temperature or below, but cannot readily be isolated without decomposition. Fluoroborates, ArN2 BF4 , are more stable (cf. stabilising effect of BF on other ion pairs, p. 136) and can be isolated in the dry solid state thermolysis of the dry solid is an important preparative method for ffuoroarenes ... 

Bimolecular reactions of the ion-radical pair can also effectively compete with the back electron transfer if either component undergoes a rapid reaction with an additive that is present during the ET activation. In NO+/arene systems, the introduction of oxygen rapidly oxidizes even small amounts of nitric oxide to compete with back ET and thus successfully effect aromatic nitration [60]. In a related example, the CT complex of hexamethylbenzene and maleic anhydride reaches a photostationary state with no productive reaction. However, if irradiation is carried out in the presence of an acid, the anion radical in the resulting contact ion-radical pair is readily protonated, and the redox equilibrium is driven toward coupling (in competition with the back ET) to yield the photoadduct [59], i.e. ... 

The most common reason for reducing aromatic nitro compounds is to make substituted anilines. Much of this chemistry was developed by the dye industry, which uses aniline derivatives for azo coupling reactions (Section 19-17) to make aniline dyes. Nitration of an aromatic ring (by electrophilic aromatic substitution) gives a nitro compound, which is reduced to the aromatic amine. 

The main emphasis of this chapter will be on our attempts to find evidence for radical coupling in reactions of the thianthrene cation radical (Th +) with nucleophiles, that is, for the occurrence of steps such as equations 7 and 8. However, because discussions of reactions of cation radicals with radicals are relatively sparse, we will refer first to other works that principally deal with aromatic nitration. 

In the Gas Phase. Schmitt et al. (32, 33) found that ArH + and N02 couple in the gas phase to give the a complex (ArHN02) +. The ArH + was produced by ionization of ArH with photons emitted from pulse-radiation excited argon atoms. Reactions were carried out in a flow system within the source of a quadrupole mass spectrometer. In contrast, reactions of the corresponding ArH with N02+ were found not to go directly to (ArHN02) + but to lead either to ArH + and N02 by fast electron transfer or to (ArHO) + and NO by oxygen-atom transfer. From these results, Schmitt et al. (32, 33) concluded that aromatic radical cations are a plausible intermediate in the mechanism for aromatic nitration. ... 

Electrophilic aromatic substitution reactions are a very important class of chemical reactions that allow the introduction of substituents on to arenes by replacing a hydrogen atom covalently bonded to the aromatic ring structure by an electrophile. The most common reactions of this type are aromatic nitrations, halogenations, Friedel-Crafts alkylations and acylations, formylations, sulfonations, azo couplings and carboxylations - to name just a few. 

Aromatic amines are usually very reactive towards electrophilic reagents yielding derivatives substituted at carbon atoms. Reactions such as nitration and bromination can be applied to the amine as such, or to the amine previously protected at the nitrogen site. Although the derivatives from these reactions are useful for identification and possibly quantitative purposes, the site and stoichiometry of the substitution are specific for every system, and no generalisation can be made. Aryldiazonium salts undergo coupling reactions with aromatic amines to yield azo dyes, which can be used for detection and determination. In Table 12 some of the aryldiazonium salts used in analysis are listed. 

A careful choice of the reaction conditions are of importance. The highest yields were observed when 1 equivalent of CAN was used, while no reaction was observed when the substrate was treated with 2 equivalents of CAN. The reaction only proceeds in aprotic solvents like acetonitrile in which CAN can be solubilized. No reaction was observed in dichloromethane, carbon tetrachloride or tetrahydrofuran, whereas the use of water, methanol or even mixtures of these solvents with acetonitrile yielded A,A,A, A/ -tetraalkylbenzidines as the result of a coupling reaction. In fact the coupling of A,A-dialkylanilines by CAN (2 eq. for 1 eq. of substrate) in water is an efficient method for the synthesis of N,N,N, N tetraalkylbenzidines (Xi et al., 2005). The yields of the nitration reactions were low when a chlorine substituent was present on the phenyl ring at the same time partial dealkylation of the amine group was observed. The reaction did not proceed when the aromatic ring contained two methyl groups in meta-posiiion. 

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

Fig. 21 Reaction scheme for the detection of aromatics, by means of the reaction sequence, nitration, reduction, diazotization and coupling to an azo dye, and of aliphatic nitro compounds by detection of the primary amino group produced on reduction.

The first step of the reaction involves nitration of the aromatic skeleton of the substance to be detected. Then the aromatic nitro derivatives so produced are reduced with sodium dithionite, in acid medium, to the corresponding amines these are then diazotized and coupled with N-(l-naphthyl)-ethylenediamine to yield an azo dye (cf. Fig. 21). 

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