Pyrroles 79-position. An N-trialkylsilyl substituent can be subsequently easily removed using fl uoride, to provide an N-hydrogen
-substituted pyrrole.
Electrophilic substitutions of pyrroles are very useful, though strong protic or Lewis acidic conditions must be avoided.
The high reactivity of the heterocycle means that such conditions would lead to rapid degradation or polymerisation.
Fortunately, this very same high reactivity means that acylations of pyrrole do not require a strong Lewis acid catalyst:
reaction with trichloroacetyl chloride, for example, requires no catalyst at all. 1-Aroylbenzotriazoles (preferred to acid
chlorides) can be used to introduce aroyl groups and require only titanium(IV) chloride as a catalyst.
A frequently used substitution is the Vilsmeier reaction, which effi ciently forms pyrrole aldehydes.
C-Alkylation of pyrroles proceeds easily with ,-conjugated ketones. Using the Mannich reaction, dialkylaminoalkyl-
pyrroles are formed (the electrophile is an iminium ion, e.g., CH 2 =NMe 2 , conveniently formed in situ). Pyrroles also
react readily with O-protonated aldehydes and ketones, though simple hydroxyalkyl substitution products cannot usu-
ally be obtained, as such compounds react further in the presence of acid (see pages 82–83).
It can sometimes be of benefi t to moderate the high reactivity of pyrrole while at the same time requiring (allowing) the
use of slightly more vigorous reagents. The presence of electron-withdrawing groups on the nitrogen or on a carbon
achieves this end. For example, clean 2,5-dibromination of 1-(t-butoxycarbonyl)pyrrole (Boc-pyrrole) can be achieved
with N-bromosuccinimide. N-Tosylpyrrole can also be dibrominated, but at the 3- and 4-positions. Incidentally, halo-
pyrroles are intrinsically rather unstable but the presence of electron-withdrawing groups on nitrogen considerably
stabilises them and thus facilitates subsequent manipulations.
Strong electron-withdrawing groups on carbon can, additionally, modify the regioselectivity of electrophilic attack.
For example, a synthesis of methyl 4-nitropyrrol-2-ylcarboxylate involves nitration of 2-trichloroacetylpyrrole. The
acyl group selectively deactivates the C-3 and C-5 positions and this infl uence overrides the intrinsic pyrrole tendency
for-substitution and attack takes place meta to the chloroacetyl group. Methanolysis of the trichloroacetyl substitu-
ent produces the ester.