Pyrrole, acylation halogenations

The chemistry of pyrrole is similar to that of activated benzene rings. In general, however, the heterocycles are more reactive toward electrophiles than benzene rings are, and low temperatures are often necessary to control the reactions. Halogenation, nitration, sulfonation, and Friedel-Crafts acylation can all be accomplished. For example ... 

Typical electrophilic reactions, such as nitration, halogenation with a Lewis acid (as a carrier ), Friedel-Crafts C-alkylation and -acylation, that work well with benzene, cannot be applied to pyrrole, because heating with strong acids, or a Lewis acid, destroys the heterocycle. However,... 

Side-chain halogenation of alkyl or acyl groups on pyrrole can occur under conditions in which the ring is fully substituted, or when radical promotors are present, especially with NBS as the reagent (89SC2721). 

A wide variety of substituents are tolerated. The group R can be alkyl, halogen, alkoxy, -amido, azi-domethyl, ester, aryl, aryloxy and aryloyl, and at least one ortho substituent is permissible with no loss in yield. TTie aromatic ring can also be 2-naphthyl, 9,10-dihydro-2-phenanthryl, 3-pyridyl, thiophen-2-yl or pyrrol-3-yl. The group R can be hydrogen, yl, acyl or acetic acid. Beyond Ae antiinflammatory targets, successful reaction substrates include the methyl ketones of a binaphthyl crown ether, a morphinane and a polyaromatic hydrocarbon. The preparation of ibuprofen methyl ester (38) is shown in equation (37) as a typical example. ... 

Instead, these heterocycles and their derivatives most commonly undergo electrophilic substitution nitration, sulfonation, halogenation. Friedel-Crafts acylation, even the Reimer-Tiemann reaction and coupling with diazonium salts. Heats of combustion indicate resonance stabilization to the extent of 22-28 kcal/ mole somewhat less than the resonance energy of benzene (36 kcal/mde), but much greater than that of most conjugateci dienes (about Tlccal/mole). On the basis of these properties, pyrrole, furan, and thiophene must be considered aromatic. Clearly, formulas I, II, and III do not adequately represent the structures of these compounds. 

Reactivity First and foremost, porphyrins are aromatic molecules. For example, they undergo some of the electrophilic substitution reactions characteristic of aromatic compounds—nitration, halogenation, sulphona-tion, formylation, acylation, and deuteration. Porph)nins differ from molecules such as benzene, in that there are two different sites on the macrocycle where electrophilic substitution can take place with different reactivities the meso-position and the pyrrole p-position. Which of these... 

In many ways the chemistry of indole is that of a reactive pyrrole ring with a relatively unreactive benzene ring standing on one side—electrophilic substitution almost always occurs on the pyrrole ring, for example. But indole and pyrrole differ in one important respect. In indole, electrophilic substitution is preferred in the 3-position with almost all reagents whereas it occurs in the 2-position with pyrrole. Halogenation, nitration, sulfonation, Friedel—Crafts acylation, and alkylation all occur cleanly at that position. 

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