Directing effects of the ring heteroatom

Monocyclic five-membered heteroaromatics with one heteroatom all undergo preferential a rather than 3 electrophilic substitution. This is rationalized in terms of the more effective delocalization of charge in the intermediate (51) leading to a substitution than in the intermediate (52) leading to 3 substitution. 

However, these considerations apply to reactions in solution. In the dilute gas phase, where the intrinsic orientating properties of pyrrole can be examined without the complication of variable phenomena such as solvation, ion-pairing and catalyst which are attendant on electrophilic substitution reactions in solution, preferential (3-attack occurs on pyrrole. In gas phase t-butylation, the relative order of reactivity at (3-carbon, a-carbon and nitrogen is 10.3 3.0 1.0 (81CC1177). 

The a directing effect of the heteroatom in furan thiophene selenophene pyrrole. The a-directing effect in tellurophene is also pronounced (77AHC(2l)ll9). 

Possible reasons for the high regioselectivity of furan in electrophilic substitution reactions include complex formation between substrates and reagents and the ability of heteroatoms to assist in the stabilization of cationic intermediates (80CHE1195). 

Positional selectivity in electrophilic substitution reactions, including methods of orientation control have been reviewed (94H(37)2029). 

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