Aromatic ring rearrangements

Extensive work by Smiles and his collaborators and by other groups clarified the main features of the rearrangement involving nitro-, sulfonyl- and halo-substituted aromatic rings. Rearrangement of 2-amino-pyridine derivatives has also been extensively studied. Reactions involved the replacement of hetero-substituents, a C - O bond by a C - N bond (N - 0), C - S by C - N (N - S) and C - S by C - O (O - S), etc. Early work has been reviewed by Bun-nett [3] (1951) and Truce [4] (1970). 

Because acylation of an aromatic ring can be accomplished without rearrangement it is frequently used as the first step m a procedure for the alkylation of aromatic compounds by acylation-reduction As we saw m Section 12 6 Friedel-Crafts alkylation of ben zene with primary alkyl halides normally yields products having rearranged alkyl groups as substituents When a compound of the type ArCH2R is desired a two step sequence IS used m which the first step is a Friedel-Crafts acylation... 

Carbocations usually generated from an alkyl halide and aluminum chloride attack the aromatic ring to yield alkylbenzenes The arene must be at least as reactive as a halobenzene Carbocation rearrangements can occur especially with primary alkyl hal ides... 

Many variations of the reaction can be carried out, including halogenation, nitration, and sulfonation. Friedel-Crafts alkylation and acylation reactions, which involve reaction of an aromatic ling with carbocation electrophiles, are particularly useful. They are limited, however, by the fact that the aromatic ring must be at least as reactive as a halobenzene. In addition, polyalkylation and carbocation rearrangements often occur in Friedel-Crafts alkylation. 

Step 3 of Figure 27.14 Third Cyclization The third cationic cyclization is somewhat unusual because it occurs with non-Markovnikov regiochemistry and gives a secondary cation at C13 rather than the alternative tertiary cation at C14. There is growing evidence, however, that the tertiary carbocation may in fact be formed initially and that the secondary cation arises by subsequent rearrangement. The secondary cation is probably stabilized in the enzyme pocket by the proximity of an electron-rich aromatic ring. 

In the first mechanism (equation 74) the nucleophile function attacks the aromatic ring in an ipso-type displacement involving a Meisenheimer complex intermediate243,244, and leads to the rearranged product after expulsion of sulfinate anion (X-). This mechanism should be favoured by the presence of an electron-withdrawing substituent in conjugation with the anion. The second mechanism (equation 75) involves a direct displacement of sulfinate anion (X ) by Y-, without involvement of the aromatic n electrons. 

In one of its earliest applications, Horner and Binder143 prepared a variety of allenyl aryl sulfoxides by the rearrangement of propargylic arenesulfenates, and noticed that accumulation of electron-withdrawing groups in the aromatic ring retard the rate of rearrangement. These authors have also performed a detailed study of the chemistry of... 

These findings are in agreement with a partial rearrangement of the charge distribution within the aromatic ring as is shown in Scheme 15. 

SO the Sgl mechanism and not the usual arenium ion mechanism is operating. Aromatic rings can also be deuterated by treatment with D2O and a rhodium(III) chloride or platinum catalyst or with CeDs and an alkylaluminum dichloride catalyst," though rearrangements may take place during the latter procedure. Tritium ( H, abbreviated T) can be introduced by treatment with T2O and an alkylaluminum dichloride catalyst. " Tritiation at specific sites (e.g., >90% para in... 

Carbenes are so reactive that they add to the double bonds of aromatic rings. The products are usually not stable and rearrange to give ring expansion. Carbene reacts with benzene to give cycloheptatriene ... 

The wide range of oxidations catalyzed by cytochrome P450 is illustrated by the examples given in Figure 2.5. Aromatic rings are hydroxylated, as in the case of 2,6 -dichlorobiphenyl. The initial product is usually an epoxide, but this rearranges... 

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