HOMO-LUMO approach to Electrophilic reactivity in
Heterocyclic Rings
The site of electrophilic substitution in heterocyclic aromatic
rings can be modelled by inspecting the calculated form of the
HOMO molecular orbital. The following are the HOMO orbitals for
a selection of heterocyclic rings. Notice how the larger
contribution to the HOMO for furan, pyrrole, thiophene and
benzothiophene all come from the C-2 carbon, whereas with
benzofuran and indole it is at C-3. This all accords with the
known reactivity of these systems. The origins of these effects
can be traced to the nodal characteristics of the HOMO, and
where the best position to place an electronegative atom is in
relation to these nodes. It also relates to the size of the
overlap between the adjacent p-p
orbitals.
For comparison, the relative energies of the Wheland
intermediate resulting from protonation (the model
electrophile) are shown, 3-substituent first, 2-substituent
second, calculated using the AM1 method.
furan (3:182.2/2:174.1) |
pyrrole (3:199.7/2:200.4) |
thiophene (3:199.7/2:200.5) |
|
|
|
benzofuran (3:192.4/2:189.3) |
indole (3:206.7/2:218.2) |
benzothiophene (3:205.5/2:214.3) |
|
|
|
To demonstrate the 3D nature of these orbitals, each
thumbnail image below is linked to a 3DMF file. To view these
orbital models, you will need a 3DMF viewer such as the Quick3D or 3DMFPlugin (both browser plugins), 3DMF
Optimizer (a Macintosh application), Geo3D (for Mac)
or 3DMF Viewer for Windows. Windows users
must also install the
QuickDraw3D libraries from Apple.