Reactions of Five-Membered Heterocycles

The reactivity of the five-membered heterocycles pyrrole, furan, thiophen and imidazole (Fig. 8-10) is characterised by interactions with electrophilic reagents. The precise nature of these reactions depends upon the particular ring system. Thiophens undergo facile electrophilic substitution, whereas the other compounds exhibit a range of polymerisation and other Lewis acid-initiated reactions upon treatment with electrophiles. We saw a number of examples of Lewis acid-promoted reactions of furans and pyrroles in Chapter 6. Although reactions of complexes of five-membered heterocyclic ligands have not been widely investigated, a few examples will illustrate the synthetic potential. 

Similar electrophilic reactions occur when 8.8 is treated with bromine water. At low temperature the 4,5-dibromoimidazole complex 8.10 is obtained, whilst at higher temperature and after longer reaction times the 2,4,5-tribromoimidazole complex 8.11 is formed. Detailed mechanistic studies suggest that the important step is the reaction of a deprotonated co-ordinated imidazole ligand with molecular bromine. 

When pyrroles are treated with strong acids, a mixture of tarry polymeric products is obtained, whilst the reaction of the complex 8.12 with a mixture of concentrated nitric and sulfuric acids yields the trinitrated product 8.13. The deprotonation of the co-ordinated pyrrole is, once again, important. The complex 8.12 also undergoes a facile deuterium exchange to give 8.14. 

Although brominated derivatives of the five-membered heterocycles may be prepared by reactions of the co-ordinated ligands, these may then undergo further reactions with nucleophiles. As an example, the nucleophilic displacement of bromide from 8.15 by sulfide has been used to form new macrocyclic systems (Fig. 8-12). The palladium probably serves a dual function in this reaction. First, it organises the open-chain ligand such that the two reactive sites are held in proximity, so allowing the intramolecular formation of the sulfide and, second, it may activate the pyrrolic ring to nucleophilic displacement of bromide. 

The activation of the co-ordinated ligands towards attack by nucleophiles is also seen in the displacement of nitrite from 8.16 by the very weakly nucleophilic chloride ion (Fig. 8-13). This displacement occurs when the complex is treated with aqueous sodium chloride solution  

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Numerous other aldehyde condensation reactions of five-membered heterocycles have been utilized in the synthesis of the central pyridine core. Paulmier and co-workers employed the condensation of 3-aminothiophenes 114 with aldehydes to give bis-thiophenylpyridines 115 (Equation 25) <1996JHC9>. 

The reaction of five-membered heterocycles with acetylenecarboxylates under conditions of cycloaddition occasionally yielded bicyclic intermediates which rearranged to the ring expanded products on heating compare examples (1) and (2) in Scheme IV/11, and Chapter III, Scheme III/4. If more polar starting materials (Scheme IV/11, entries 3 and 4) are used, it is not possible to... 

To explain the noncorrespondence in the series of substrate and positional selectivities in electrophilic substitution reactions of five-membered heterocycles with one heteroatom, a hypothesis was put forward (79MI2, 80KGS1587). Namely, the formation of jS-substituted... 

The reactions of five-membered heterocycles with two or more heteroatoms cannot be classified as easily as those systems possessing only one heteroatom. For this reason, they are described according to the system and importance of their reactions. For oxazoles, the following reactions are characteristic [67]. 

Scheme 35 Diels—Alder reaction of five-membered heterocycles with acrolein (X = NMej, OMe, COOMe, CN Y = NH, O, PH, S).

Figure 2. Global electropolymerization reaction of five-membered heterocycles and / -doping/undoping reaction.

A variety of photoinduced electron transfer reactions leading to the alkylation of heteroaromatic compounds are known. A typical example involves the reaction of five-membered heterocycles with electron-rich alkenes as illustrated in Scheme 9 Thus, photolysis of furans in the presence of 1,1-diarylethenes and a sensitizer (such as 1-cyanonaphthalene) gives alkylated products in good yield following an unusual... 

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