Pyrroles typical reactivity

Entrapment of biochemically reactive molecules into conductive polymer substrates is being used to develop electrochemical biosensors (212). This has proven especially useful for the incorporation of enzymes that retain their specific chemical reactivity. Electropolymerization of pyrrole in an aqueous solution containing glucose oxidase (GO) leads to a polypyrrole in which the GO enzyme is co-deposited with the polymer. These polymer-entrapped GO electrodes have been used as glucose sensors. A direct relationship is seen between the electrode response and the glucose concentration in the solution which was analyzed with a typical measurement taking between 20 to 40 s. 

Nevertheless, we can interpret the reactions of furan and thiophene by logical consideration as we did for pyrrole. In electrophilic substitutions, there is again a preference for 2- rather than 3-substitution, and typical electrophilic reactions carried out under acidic conditions are difficult to control. However, because of lower reactivity compared with pyrrole, it is possible to exploit Friedel-Crafts acylations, though using less-reactive anhydrides rather than... 

We have presented evidence that pyrrole-2-carboxylic acid decarboxylates in acid via the addition of water to the carboxyl group, rather than by direct formation of C02.73 This leads to the formation of the conjugate acid of carbonic acid, C(OH)3+, which rapidly dissociates into protonated water and carbon dioxide (Scheme 9). The pKA for protonation of the a-carbon acid of pyrrole is —3.8.74 Although this mechanism of decarboxylation is more complex than the typical dissociative mechanism generating carbon dioxide, the weak carbanion formed will be a poor nucleophile and will not be subject to internal return. However, this leads to a point of interest, in that an enzyme catalyzes the decarboxylation and carboxylation of pyrrole-2-carboxylic acid and pyrrole respectively.75 In the decarboxylation reaction, unlike the case of 2-ketoacids, the enzyme cannot access the potential catalysis available from preventing the internal return from a highly basic carbanion, which could be the reason that the rates of decarboxylation are more comparable to those in solution. Therefore, the enzyme cannot achieve further acceleration of decarboxylation. In the carboxylation of pyrrole, the absence of a reactive carbanion will also make the reaction more difficult however, in this case it occurs more readily than with other aromatic acid decarboxylases. 

Although the reactivity of enaminones is not always the same as that of typical enamines due to the additional conjugative interaction with the carbonyl group, the anodic oxidation of enaminones seems useful in organic synthesis since they yield dimerized or cyclized products upon anodic oxidation. In anodic oxidation of the enaminones or enaminoesters in methanol containing sodium perchlorate, for instance, derivatives of pyrrole are formed via initial dimerization (equation 4)5. 

The TTyir singlet states of the cyclopropenes (101) are reactive and lead to re2irrangement products by way of a carbene (102) mechanism as outlined above. Typical examples of the reaction are shown in the Scheme 8, where it can be seen that the rearrangement affords the isomeric substituted furans (103) and (104) from (101, X = 0) and pyrroles (105) and (106) from (101, X =NMe). This latter reaction also yields the diene-substituted pyrrole (107), which is good evidence for the proposed carbene mechanisms. The thiophene derivative (101, X = S) yields a single product (108) on photoexcitation. 

---