Benzene reaction with electrophiles

Section 12.1 On reaction with electrophilic reagents, compounds that contain a benzene ring undergo electrophilic aromatic substitution. Table 12.1 in Section 12.1 and Table 12.3 in this summai-y give exanples. 

The reactivity of Ce, C7, Cg aromatics is mainly associated with the benzene ring. Aromatic compounds in general are liable for electrophilic substitution. Most of the chemicals produced directly from benzene are obtained from its reactions with electrophilic reagents. Benzene could be alkylated, nitrated, or chlorinated to important chemicals that are precursors for many commercial products. 

After the optimization of the conditions for the production of o-bromophenyl-lithium to —78°C with a 0.8 s residence time, the scope was extended to sequential Br-Li exchange of both bromine substituents on the benzene ring and the reaction with electrophiles to form o-disubstituted benzene rings. This was done in a four-step reaction in one flow using four-linked microreactors (MRi ). For the second lithiation, the temperature of 0°C was sufficient, which was expected since the aryllithium intermediate is more stable than o-bromophenyllithium. 

Few reports describe reactions of substituents at the benzene ring of benzotriazoles. The facile deprotonation of the methyl group in N-Boc-7-methyl-1-aminobenzotriazole (403) with butyllithium followed by reactions with electrophiles gives substituted products (404) (Scheme 78). The electrophile can be an alkyl halide, an aldehyde or a ketone, and the Boc group is removed by brief exposure to CF3CO2H in CH2CI2 <93TL6935>. 1-Acetylbenzotriazole (405) is hydrolyzed to form 3-(177-5-hydroxybenzotriazol-6-yl)propionic acid (406), which is then converted (Scheme 79) to... 

An electrophile — an electron-seeking reagent — is generated. For the bromination of benzene reaction, the electrophile is the Br+ ion generated by the reaction of the bromine molecule with ferric bromide, a Lewis acid. 

These structures suggest that the carbons in pyridine are partially positively charged (due to the electron-withdrawing effect of the nitrogen) and, therefore, are expected to be deactivated (relative to benzene) toward reaction with electrophiles. Note that the positive charge is distributed between carbons 2, 4, and 6. Therefore, these carbons should be less reactive toward electrophiles than carbon 3 (or 5). 

The vast majority of reactivities and regioselectivities observed in the reaction with electrophiles on monosubstituted benzenes (Table 5.2) are in agreement with the preceding generalizations (columns 2 and 4). The very few substituents that are not in agreement (column 3) deactivate the aromatic compound as do electron acceptors, but they are para- > ortho-directing as are electron donors. 

The positively charged nitrogen inductively withdraws electron density from the aromatic ring. This aromatic ring is less electron-rich than benzene, so it is deactivated toward reactions with electrophiles. 

The perfluorobenzyl organometallic analog, (perfluorobenzyl)cadmium halide (C(,F5CF2CdX), can be prepared in a similar fashion by direct reaction of perfluoro[(bromomethyl)benzene] and acid-washed cadmium powder in dimethylformamide at room temperature. The cadmium reagent is stable at room temperature for several days, but starts to decompose at 50 C. Like (perfluoroallyl)cadmium, (perfiuorobenzyl)cadmium undergoes functionalization reactions with electrophiles such as iodine and allyl bromide. 

Groups (Z) in which the atom attached to the benzene ring possesses a lone pair of electrons can interact with the aromatic ring as shown in 6, promoting ortho and para attack. The ring becomes more electron rich and so the reaction with electrophiles is facilitated. You can think of the lone pair of electrons as being formally located at the ortho and para positions. 

Is Cgo aromatic Although it is completely conjugated, it is not planar. Because of its curvature, it is not as stable as benzene. In fact, it undergoes addition reactions with electrophiles in much the same way as ordinary alkenes. Benzene, on the other hand, undergoes substitution reactions with electrophiles, which preserves the unusually stable benzene ring intact. These reactions are the subject of Chapter 18. 

Alkylidenecycloproparenes (benzotriafulvenes) are more strained than triafulvenes and readily undergo ring opening or rearrangement upon reaction with electrophiles and nucleophiles. For cycloadditions, different reactivity has been observed between diarylmethylenecyclopropa-benzenes 12 and -naphthalenes 13. While the former compounds give Diels-Aldcr adducts at the endocyclic double bond with diphenylisobenzofuran, the latter compounds produce rearrangement products via Diels-Alder adducts from reaction at the exocyclic C —C double bond. A [2-1-2] cycloaddition has also been observed for a naphtbo compound. 

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