Benzene derivatives electrophilic aromatic

SYNTHESIS OF BENZENE DERIVATIVES ELECTROPHILIC AROMATIC SUBSTITUTION... 

The reaction of quinoline (78) with bromine and sulfuric acid gives a bromi-nated quinoline derivative via reaction with Br+, but where Note that quinoline is a base, and it will react with sulfuric acid to form an ammonium salt. Remember that pyridine is much less reactive than benzene in electrophilic aromatic substitution reactions. Therefore, assume that the ring containing nitrogen is much less reactive. This leaves C5-C8 as potential sites for electrophilic substitution. Indeed, 78 reacts with bromine and srdfuric acid to give a mixture of 5-bromoquinoline and 8-bromoquinoline, with 5-bromoquinoline being the major product. ... 

In another study, Arkin and Hazer modified the PHA-Cl into quaternary ammonium salts, thiosulfate moieties and phenyl derivatives. In addition, they cross-linked the modified PHA-Cl with benzene by electrophilic aromatic substitution using a Friedel-Crafts reaction. The random composition of PHA-Cl was calculated from its H NMR spectrum by comparing the relative peak areas of the methine protons on the polymer backbone. Hence, increased chlorination of the methyl protons caused the peak of methine protons to be moved further downfield. In addition, the PHA-Cl mole fractions were calculated by comparing the peak areas of protons on chlorinated a-carbons and protons on p-carbons. Samsuddin et al. ° described a process for the direct fluorination of PHBHHx at elevated pressure in the... 

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, selenophene[233,234], and cyclobutadiene iron carbonyl complexpSS] react with alkenes to give vinyl heterocydes. The ease of the reaction of styrene with sub.stituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

Reduction of arenes by catalytic hydrogenation was described m Section 114 A dif ferent method using Group I metals as reducing agents which gives 1 4 cyclohexadiene derivatives will be presented m Section 1111 Electrophilic aromatic substitution is the most important reaction type exhibited by benzene and its derivatives and constitutes the entire subject matter of Chapter 12... 

The scope of electrophilic aromatic substitution is quite large both the aromatic com pound and the electrophilic reagent are capable of wide variation Indeed it is this breadth of scope that makes electrophilic aromatic substitution so important Elec trophilic aromatic substitution is the method by which substituted derivatives of benzene are prepared We can gam a feeling for these reactions by examining a few typical exam pies m which benzene is the substrate These examples are listed m Table 12 1 and each will be discussed m more detail m Sections 12 3 through 12 7 First however let us look at the general mechanism of electrophilic aromatic substitution... 

Phenol and anisole are among the commonly encountered benzene derivatives listed in Table 11.1. Electrophilic aromatic substitution in phenol is discussed in more detail in Section 24.8. 

In a first reaction step the formaldehyde 2 is protonated, which increases its reactivity for the subsequent electrophilic aromatic substitution at the benzene ring. The cationic species 4 thus formed loses a proton to give the aromatic hydroxymethyl derivative 5, which further reacts with hydrogen chloride to yield the chloromethylated product 3 ... 

The y-nitrogen atom of a sulfonic acid azide is electrophilic and reacts in an electrophilic aromatic substitution with an activated benzene or naphthalene derivative, e.g., a phenoxide ion, forming a l-tosyl-3-aryltriazene (2.47). The 1,4-quinone diazide is obtained by hydrolysis (Scheme 2-30, Tedder and Webster, 1960). The general applicability of this reaction seems to be doubtful. With 1-naphthol the 1,2-naphthoquinone diazide was obtained, not the 1,4-isomer. 

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. 

Electrophilic addition reactions. See also Addition reactions with butylenes, 4 405-408 of maleic anhydride, 75 490 with methacrylic acid/derivatives, 76 236-237 of propylene, 20 774 Electrophilic aromatic substitution, benzene, 3 599-601 Electrophilic attack, at nitrogen and carbon, 27 98... 

The figure represents the chemical structure for paracetamol, which includes the N-(4-hydroxyphenyl) acetamide, derived from the interaction of p-aminophenol and an aqueous solution of acetic anhydride. The structure has two activating groups that make the benzene ring highly reactive toward electrophilic aromatic substitution. 

In the thermal decomposition of 45 in aniline and A -methylaniline, the carbene 54 showed electrophilic reactivity together with hydrogen abstraction ability (84JOC62). In fact, 48 [R = NHPh, N(Me)Ph], products of A -pyrrylation of anilines, together with 48 (R = H), a product of hydrogen transfer to 54, were obtained. In this case, aromatic substitution, typical of electron-rich benzene derivatives, was not observed. The formation of both A -pyrrylated anilines, evidence of involvement of 54s, and the... 

M n Part II we spend a lot of time and pages on aromatic systems, starting with benzene. You examine benzene s structure, its resonance stabilization, and its stability. Next you study benzene derivatives and heterocyclic aromatic compounds, and then we address the spectroscopy of these aromatic compounds. And in Chapters 7 and 8 we introduce you to aromatic substitution by both electrophiles and nucleophiles, and you get to see a lot of reactions and a lot of examples. In this part you also start working with many more named reactions. 

Aniline is an important derivative of benzene that can be made in two steps by nitration to nitrobenzene and either catalytic hydrogenation or acidic metal reduction to aniline. Both steps occur in excellent yield. Almost all nitrobenzene manufactured (97%) is directly converted into aniline. The nitration of benzene with mixed acids is an example of an electrophilic aromatic substitution involving the nitronium ion as the attacking species. The hydrogenation of nitrobenzene has replaced the iron-... 

Since benzenesulfonyl peroxide was used as an initiator in polymerization reactions, it was thought that a free radical aromatic substitution of benzene by the benzenesulfonoxy radical takes place. A detailed study by Dannley and Knipple reveals that attachment of the sulfonoxy group derived from a bis(arylsulfonyl) peroxide to the aromatic ring occurs by electrophilic aromatic substitution (equation 5) °. 

Trifluoromethyl)benzene (benzotrifluoride, 15) was the first organic fluoride to incorporate a trifluoromethyl group. By a standard nitration process, it formed l-nitro-3-(trifluoromethyl)-benzene (16) which was reduced to the 1-amino derivative, 17. This we a-directive influence on electrophilic aromatic substitution contrasted with that for fluorobenzene, which gave 4-and 2-nitro products. 

The fact that benzene derivatives are much more generally accessible than pyrroles has relegated pyrrole annelation to a relatively minor role in indole synthesis. Nevertheless the concept provides a viable synthetic approach and the existing methods serve as useful prototypes. One strategy is to build up an appropriately functionalized side-chain and complete indole formation by electrophilic substitution-aromatization. Reactions (135)-(137) illustrate this type of approach (79TL3477, 79JA257, 73JPR295). 

The partial rate factors af and /3f for the a- and /3-positions of thiophene have been calculated for a wide range of electrophilic reactions these have been tabulated (71 AHC(13)235, 72IJS(C)(7)6l). Some side-chain reactions in which resonance-stabilized car-benium ions are formed in the transition states have also been included in this study. A correspondence between solvolytic reactivity and reactivity in electrophilic aromatic substitution is expected because of the similar electron-deficiency developed in the aromatic system in the two types of reactions. The plot of log a or log /3f against the p-values of the respective reaction determined for benzene derivatives, under the same reaction conditions, has shown a linear relationship. Only two major deviations are observed mercuration and protodemercuration. This is understandable since the mechanism of these two reactions might differ in the thiophene series from the benzene case. 

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