Reactions of substituents on benzene rings

Substituents on fused benzene rings undergo the usual reactions expected in the benzene series. The orientation in the diazo coupling reactions with hydroxy compounds (300) and (301) indicates that there is little bond fixation in dibenzofuran, a distinct contrast to naphthalene. 

4-Alkylaminoindoles (302) rearrange to 4-amino-l-alkylindoles (303) when heated with p-toluenesulfonic acid hydrate (82CC1356). 

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Substituents directly attached to fused benzene rings or aryl groups mostly show the reactions of those on benzenoid rings. Thus, a substituent on the benzenoid ring in quinoline or isoquinoline should be compared with that on a naphthalene rather than with a benzene nucleus for example, such hydroxy derivatives undergo the Bucherer reaction, ArOH + (NH4)2S03 ArNH2, typical for naphthols (see also Section 3.2.3.2.2). 

This reaction has the advantage that only one product (11) (head-to-head coupling product) is formed. Additional results are shown in Table 5. Aromatic bromides and iodides easily react with vinylic boron compounds, but organic chlorides do not participated, except the reactive allylic and benzylic derivatives. Heteroaromatic halides can be used as coupling partners. Or// o-substituents on benzene ring do not give difficulty. Thus, the cross-coupling reaction is used for the synthesis of benzo-fused heteroaromatic compounds (eq 5) (6). 

If the reactions of the same substituents on heteroaromatic azoles and on benzene rings are compared, the differences in the reactivities are a measure of the heteroatoms influence. Such influence by the mesomeric effect is smaller when the substituent is /3 to a heteroatom than when it is a or y. The influence by the inductive effect is largest when the substituent is a to a heteroatom. 

In extension of the alkylation reactions to polychlorobenzenes, polychlorinated benzenes such as 1,2,4-trichlorobenzene and 1,2,., 4-tetrachlorobenzene were alkylated with (l,2-dichloroethyl)trichlorosilanes in the presence of aluminum chloride catalyst. Although the electron-withdrawing chlorine substituents on the ring deactivated the electrophilic substitution reaction, the alkylation... 

Rehahn et al. [35] recently presented the synthesis of constitutionally homogeneous oligophenylenes, 22a/b, with 2,5-alkyl substituents located on the central aromatic ring, generated via the cross-coupling reaction of Suzuki. They are exclusively linked in the para-positions and composed of 3 -15 benzene rings. 

This diazotization reaction is compatible with the presence of a wide variety of substituents on the benzene ring. Arenediazonium salts are extremely important in synthetic chemistry, because the diazonio group (N=N) can be replaced by a nucleophile in a radical substitution reaction, e.g. preparation of phenol, chlorobenzene and bromobenzene. Under proper conditions, arenediazonium salts react with certain aromatic compounds to yield products of the general formula Ar-N=N-Ar, called azo compounds. In this coupling reaction, the nitrogen of the diazonium group is retained in the product. 

With this section, the classification in the Handbook of Heterocyclic Chemistry has been followed thus a general survey of the effect of rings on the reactions of substituents is followed by a survey of the effect of rings on reactions of individual substituents in the order fused benzene rings, C-linked, AMinked, <9-linked, S-linked substituents, halogens, and metals. Substituents attached to cyclic nitrogen and sulfur are dealt with as described below. 

The best method of generating thienyl radicals is by photolysis of iodothiophenes (Scheme 171) (731JS295). Iodothiophenes bearing other substituents on the ring have been successfully utilized for thienylation reactions. Photolysis in benzene gave 80-90% yields of the required phenylthiophenes. 

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