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Aromatic and Saturated Heterocycles

Aromatic Five-Membered Heterocyclic Compounds

The doubly unsaturated five-membered heterocyclic compounds have specific characteristics. Their chemical behavior resembles aromatic compounds as well as non-aromatic dienes. However, substitution reactions are to be found rather than addition reactions. The NMR spectra indicate a more or less strong aromatic ring current. What is the explanation for these chemical properties?

Five-membered heterocycles interpreted as butadiene derivatives

On one hand, the aromatic five-membered heterocycles are considered to be 1,3-butadiene derivatives. The diene-like chemical behavior may be illustrated in such a way. However, the question is how the aromaticity of these compounds is to be explained?

Cyclopentadiene does not display an aromatic behavior. So, what is really the difference between cyclopentadiene and the aromatic five-membered heterocycles?

Comparison of cyclopentadiene with aromatic five-membered heterocycles

In contrast to cyclopentadiene's sp3 carbon, the nitrogen, oxygen or sulfur of the aromatic heterocycles possess at least one lone electron pair that occupies a p orbital perpendicular to the ring plane. Thus, this lone electron pair, or the corresponding p orbital can participate in the π system of the conjugated diene. As a result, the heterocycles contain a cyclic, continuous π system and fulfill Hückel's rule, as they possess six (6 = 4*2+2 = 4n+2, with n=1) π electrons. Furthermore, they are planar. According to the rules for aromaticity, they are aromatic compounds which may additionally be substantiated through the application of the Frost circle. The second lone electron pair of oxygen and sulfur in furan and thiophene, respectively, is located in an sp2 orbital that is parallel to the ring plane. Therefore, this electron pair cannot take part in the aromatic π electron system.

Comparison of cyclopentadiene and pyrrole by the Frost circle

Reactivity of pyrrole

In comparison to furan and thiophene, the dipole moment of pyrrole unexpectedly has the opposite direction. This is surprising, as the positive pole of pyrrole's dipole is located at the nitrogen, though nitrogen is more electronegative than carbon.

Dipol moments of pyrrole, furan, and thiophene

Why is the highest electron density of pyrrole not located at the nitrogen? The illustration of pyrrole's resonance structures makes it clear that negative charges appear at the four carbons, though not at the nitrogen, while a positive charge only appears at the nitrogen. That is, the effect of resonance on the electron distribution obviously surmounts the effect that nitrogen's higher electronegativity has on electron distribution.

Resonance structures of pyrrole

Pyrrole's chemical behavior corresponds to the electron distribution indicated by the respective resonance structures. Through a relatively weak acid, for instance, it is not the nitrogen but almost only the carbons that are protonated. The dipole moment of pyrrolidine, which is the corresponding saturated compound, is not influenced by resonance. Thus, in this case, the negative pole is located at the nitrogen.

Dipol moments of aromatic and saturated five-membered heterocycles

In furan and thiophene, the dipole moment is influenced by resonance in the same way as in pyrrole. However, the effect of resonance is obviously not sufficient enough to exceed the effect of the heteroatom's electronegativity. Thus, the negative pole is located at the heteroatom. However, due to the resonance, the dipol moments of furan and thiophene are smaller than that of the corresponding saturated heterocycles, tetrahydrofuran and tetrahydrothiophene. In the case of pyrrole, the influence of resonance on the dipole moment is so strong, that the dipole moment is inverted in comparison to the corresponding saturated heterocycle, pyrrolidine.

Electrophilic substitution at pyrrole

As is expected of an aromatic compound, pyrrole can react in electrophilic substitutions. Due to the higher electron density at the carbons, substitution takes place at a carbon instead at nitrogen. However, there are two different carbon positions. At which position does the substitution occur?

In order to answer this question, analyze the resonance structures of the conceivable σ complexes of the electrophilic substitution.

Case 1: Electrophilic substitution at C-2
Case 2: Electrophilic substitution at C-3

In comparing the resonance structures of σ complexes that arise from a C-2 and C-3 attack on an electrophile, the C-2 attack is singled out as the most favorable alternative. In the case of substitution at C-2, the σ complex can be described by three different resonance structures. If the substitution occurs at C-3, only two different resonance structures of the σ complex are possible. Thus, when substitution takes place at C-2, the stabilization through resonance is obviously stronger. The electrophilic substitution at C-2 is, practically speaking, actually favored over the C-3 substitution. However, substitution at C-3 may also occur as well, as C-3 is also activated. As a result, electrophilic substitution at pyrrole often yields product mixtures. Nitration of pyrrole, for instance, leads to 80% 2-nitropyrrole and 20% 3-nitropyrrole.

Product ratio in the nitration of pyrrole

Synthesis of substituted pyrroles, furans and thiophenes

Paal-Knoor synthesis

Unsubstituted pyrrole, furan and thiophene are usually obtained from petroleum. They may be converted into substituted aromatic heterocycles through an electrophilic substitution. However, substituted aromatic five-membered heterocycles may also be synthesized through the cyclization of 1,4-diketones in combination with ammonia (NH3), amines, phosphorus pentoxide (P2O5), or phosphorus pentasulfide (P2S5). The ring-closure is proceeded by dehydration (condensation), which then yields the two double bonds and, thus, the aromatic π system. The formation of the energetically favored aromatic system is one of the driving forces of the reaction.

Paal-Knoor syntheses
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