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Encyclopedia of Physical Science and Technology EN007F-314 July 6, 2001 16:59

Heterocyclic Chemistry 323

B. Heteroaromaticity those of the 2,3-analogs, which retain much of the aro-
maticity associated with the benzene ring.
A nitrogen atom in a ring can be neutral or can carry a
positive or a negative charge. Oxygen and sulfur atoms
Z
in a ring either are in the neutral form or carry a positive Z
charge. For aromaticity to be observed in a heterocycle,
3,4-benzoheterocycle 2,3-benzoheterocycle
electrons in an orbital perpendicular to the plane of the
ring must overlap with the pi orbitals of other atoms in The quantitative measurement and even the precise def-
that ring. The lone pair of pyrrole is in such an orbital and inition of aromaticity are problematic. One common mea-
the bonding can be expressed in the language of valence surement of aromaticity involves determining the differ-
bond theory. ences in energy, by combustion, between a heterocycle
_ and its carbocyclic analog; examples of values are given
in Table I.
_
Z Z Z N A second method involves measurement of magnetic
+ + H
ring currents induced in aromatic systems by external
valence bond representation pi orbitals of pyrrole
of pyrrole Z=NH magnetic fields. A nuclear magnetic resonance spectrom-
eter records the observed magnetic effect, which can be
Because substantial negative charge resides at all the related to the degree of aromaticity.
ring carbon atoms of pyrrole (see valence bond structures,
or canonical forms), it is referred to as a pi-excessive het-
erocycle. Owing to the excess negative charge at carbon, C. Nomenclature and Numbering
it is unsurprising that the chemistry of pi-excessive hete- of Heterocycles
rocycles is dominated by electrophilic attack. Single heterocycles are extensively referred to by their
Pyridine is more aromatic than pyrrole, but for quite dif- well-known or “trivial” names, such as pyrrole, furan, and
ferent reasons. Here, the three double bonds in the pyridine thiophene. Numbering of a monocyclic heterocycle, such
ring are markedly delocalized, and this accounts for the as thiazole,
high degree of aromaticity of pyridine (see Table I).
+ N O S
H
pyrrole furan thiophene
+ +
N N _ N _ N _
starts at the heteroatom of highest priority (oxygen taking
valence bond representation of pyridine
priority over sulfur, which takes priority over nitrogen,
etc.). Thus, morpholine and thiazine are numbered as
However, the lone pair on nitrogen is in an orbital par-
shown.
allel with the plane of the ring and hence cannot donate
negative charge into it. Because nitrogen is a strongly 1 1
O S
electronegative (electron-attracting) element, the net re- 6 2 6 2
sult is to remove electronic charge from the ring, as just 5 N 3 5 N 3
H H
depicted in the canonical forms of pyridine. For this rea- 4 4
son, pyridine undergoes electrophilic attack only under morpholine 1,4-thiazine
very forcing conditions and is referred to as a pi-deficient
In all heterocyclic systems, the prefixes “oxa,”“thia,”
heterocycle.
and “aza” denote oxygen, sulfur, and nitrogen atoms, re-
Considerations similar to the above can be applied to
spectively. Also, two, three, or four identical heteroatoms
all “aromatic” heterocycles, at least in principle. An in-
bear the prefixes di, tri, and tetra, respectively, as in
teresting series is made up of the resonance energies of
“dithia”and“triaza.”Partiallysaturatedringsareindicated
3,4-benzoheterocycles, which are substantially lower than
by the prefix “dihydro” and “tetrahydro,” etc., and/or 1H-,
2H-, etc., to identify saturated carbon(s) not taken into
TABLE I Approximate Aromatic Stabilization account by the prefixes of hydrogenation. Examples are
Energies for Benzene and Some Heteroaromatic
tetrahydrofuran and 2H-pyran.
Rings (kcal/mole)
4
4 3
Benzene 36 Pyridine 31 Pyrazine 23 5 3
Pyrrole 20 Thiophene 25 Furan 18 5 O 2 6 O 2
1
Pyrazole 25 Imidazole 20 1,2,4-Triazole 20 1
tetrahydrofuran 2H-pyran