Heterocyclic Chemistry at a Glance, Second Edition. John A. Joule and Keith Mills.
© 2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd.
Electrophilic substitution at carbon
Furan and thiophene can usefully be examined in parallel, comparing one with the other and with pyrrole. Each
of them, like pyrrole, is very much more reactive towards electrophiles than benzene. In this trio of heteroaromatic
systems, thiophene is the ‘most aromatic’ – the most like benzene – and furan is the ‘least aromatic’ – the most like a
1,3-diene. For example, thiophene undergoes normal nitration, with -selectivity (like pyrrole – see the discussion on
page 78) but furan tends to produce 2,5-dihydrofuran adducts in which the elements of the attacking agent (AcONO 2
in the case of nitration) have added to the heterocycle with a consequent loss of aromaticity. The aromatic substitution
product can be easily obtained from the adduct by base-induced loss of acetic acid.
Another example is bromination – 2-bromothiophene is obtained from thiophene, even at –5 °C, using bromine
alone, no catalyst is required – thiophene is more reactive than benzene and furan more reactive than thiophene.
Under slightly more vigorous conditions, it is easy to 2,5-di-, 2,3,5-tri- and 2,3,4,5-tetra-brominate thiophene and
2,3,5-tribromothiophene and 2,3,4,5-tetrabromothiophene can be used to access 3- or 3,4-dibromothiophenes
because zinc–acetic acid specifi cally reduces out -bromines.
Furan also reacts rapidly with bromine, but in a nucleophilic solvent, such as methanol, the initial cationic intermedi-
ate is trapped by addition of solvent. The fi nal product, 2,5-dihydro-2,5-dimethoxyfuran results from a nucleophilic
displacement of the bromine from its reactive position in the fi rst adduct, the bromine being both allylic and to
oxygen. 2,5-Dihydro-2,5-dimethoxyfuran is a synthetic equivalent of but-2-ene-1,4-dial, and its dihydro-derivative, of
butane-1,4-dial, and both of these are valuable in heterocyclic ring synthesis (see pages 58 and 83).