Pyrrole relative aromaticity

The following important conclusions can be drawn from the above results [88JST(163)173]. First, the values of [2A ]n are nearly equal for furan and pyrrole hence the correct aromaticity trend can be ascertained only if the [XAE], contributions are also taken into account. Thus, the relative aromatic character of the compounds under discussion is determined by the sum of the stabilizing effects of the two electron interactions. These are the stabilization energy AE, referring to the interaction be-... 

How does this concept of aromaticity apply to typical heterocycles such as pyridine 5.1 and pyrrole 2.1 Pyridine can formally be derived from benzene by replacement of a CH unit by an sp2 hybridised nitrogen atom. Consequently, pyridine has a lone pair of electrons instead of a hydrogen atom. However the six 7t electrons are essentially unchanged, and the pyridine is a relatively aromatic heterocycle. 

The high basicity and consequent electrophilic reactivity that hinder the determination of the reactivity of pyrrole relative to other aromatics facilitates reaction with unreactive electrophiles. This was utilized by Butler and co-workers, who measured partial rate factors for methyl substituents (Table 6.10) in coupling with benzenediazonium ions [77JCS(P2) 1452] and in alkylation by 4-(Af,ALdimethylamino)benzalde-hyde [76JCS(P2)696]. The selectivities of both reactions are remarkably similar. Reaction with p-X-benzenediazonium ions (X = OMe, CN, NO,... 

Table 42 gives an overview of annular tautomerism data for azoles in the gas phase and in solution or crystals. In the gas phase the stability of alternative tautomers largely depends on their relative aromaticities. In Section 2 A.4.2.2 it was noted that 1,2-relationships between pyrrole- and pyridine-type nitrogen atoms favor aromaticity (Figure 21) and this is consistent with the relative stabilities of triazole and tetrazole tautomers in the gas phase (Table 42) <2010T2695>. In solution (and crystals) other factors such as solvent polarity, hydrogen bonding, and temperature become important and the relative stabilities can be reversed. Polar solvents tend to stabilize the tautomer with the largest dipole moment and this probably accounts for the observation of both 2H-1,2,3-triazole (p = 0.12D) and H-1,2,3-triazole (p = 4.55D) in...

The most simple method of obtaining a porphyrin on the gram scale is to reflux a dilute benzaldehyde-pyrrole mixture in propionic acid (141°C) for 30 minutes, cool, and filter. A 20% yield of crystalline porphyrin is easy to achieve (Scheme 6.3.1) (Lindsey et al., 1987, 1994 Prathapan et al., 1993). Even pentamers have been obtained by such a reaction in one step from a porphyrin benzaldehyde building block and pyrrole. One just has to carry out the primary formation of the porphyrinogen at a relatively low concentration (10 M) and under nonoxidative conditions, which allow the rearrangement of undesired polymers. Up to 50% of the colorless porphinogens are obtained by acid-catalyzed condensation of pyrrole and aromatic aldehydes under nitrogen. 

The fact that 3-hydroxypyrazoles are always predominant in the equilibria with their corresponding CH-tautomers is related to their aromaticity. Qualitative interpretations supported the hypothesis that the NH tautomer was less aromatic than the OH tautomer, and the CH tautomer was nonaromatic. Nuclear independent chemical shifts (NICS) values were calculated by using Schleyer s approach in order to determine the relative aromaticity of the pyrazole NH and OH tautomers using pyrrole as a reference. For pyrazole itself, the NICS value was close to pyrrole (—15.1 ppm). The NICS values were found to be —14.55 ppm for the 5-OH tautomer and —14.45 ppm for the 3-OH tautomer, indicating that the OH substituent does not alter the aromaticity of pyrazole and dipolar charges are not relevant. The NH tautomer has a NICS value of —6.75 ppm, intermediate between the OH tautomers and the nonaromatic CH tautomer, the latter with a NICS value of —0.25 ppm. 

Indole is planar with 10 TT-electrons in a completely conjugated system. The ring is classified as a TT-excessive he tero aromatic compound because of the electron-donating character of the pyrrole-type nitrogen atom. The TT-system is relatively electron-rich, particularly at C-3, as represented by resonance stmcture (lb). 

Electrophilic Aromatic Substitution. The Tt-excessive character of the pyrrole ring makes the indole ring susceptible to electrophilic attack. The reactivity is greater at the 3-position than at the 2-position. This reactivity pattern is suggested both by electron density distributions calculated by molecular orbital methods and by the relative energies of the intermediates for electrophilic substitution, as represented by the protonated stmctures (7a) and (7b). Stmcture (7b) is more favorable than (7a) because it retains the ben2enoid character of the carbocycHc ring (12). 

In keeping with its aromatic character, pyrrole is relatively difficult to hydrogenate, it does not ordinarily serve as a diene for Diels-Alder reactions, and does not undergo typical olefin reactions. Klectrophilic substitutions are the most characteristic reactions, and pyrrole has often been compared to phenol or... 

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

Pyridine is a polar, stable, relatively unreactive liquid (bp 115°C) with a characteristic strong penetrating odor that is unpleasant to most people. It is miscible with both water and organic solvents. Pyridine was first isolated, like pyrrole, from bone pyrolysates. Its name is derived from the Greek for fire (pyr) and the suffix idine used to designate aromatic bases. Pyridine is used as a solvent, in addition to many other uses including products such as pharmaceuticals, vitamins, food flavorings, paints, dyes, rubber products, adhesives, insecticides, and herbicides. Pyridine can also be formed from the breakdown of many natural materials in the environment. 

In a formal sense, isoindole can be regarde,d as a IOtt- electron system and, as such, complies vith the Hiickel (4w- -2) rule for aromatic stabilization, with the usual implicit assumption that the crossing bond (8, 9 in 1) represents a relatively small perturbation of the monocyclic, conjugated system. The question in more explicit terms is whether isoindole possesses aromatic stabilization in excess of that exhibited by pyrrole. 

Individual substitutions may not necessarily be true electrophilic aromatic substitution reactions. Usually it is assumed that they are, however, and with this assumption the furan nucleus can be compared with others. For tri-fluoroacetylation by trifluoroacetic anhydride at 75 C relative rates have been established, by means of competition experiments 149 thiophene, 1 selenophene, 6.5 furan, 1.4 x 102 2-methylfuran, 1.2 x 105 pyrrole, 5.3 x 107. While nitrogen is usually a better source of electrons for an incoming electrophile (as in pyrrole versus furan) there are exceptions. For example, the enamine 63 reacts with Eschenmoser s salt at the 5-position and not at the enamine grouping.150 Also amusing is an attempted Fischer indole synthesis in which a furan ring is near the reaction site and diverted the reaction into a pyrazole synthesis.151... 

We can draw Frost circles (see Section 2.9.3) to show the relative energies of the molecular orbitals for pyridine and pyrrole. The picture for pyridine is essentially the same as for benzene, six jt electrons forming an energetically favourable closed shell (Figure 11.1). For pyrrole, we also get a closed shell, and there is considerable aromatic stabilization over electrons in the six atomic orbitals. 

The aromaticity of pyrrole, furan, and thiophene may also be assessed by considering the 7r-electron distribution in them (8UST163), which points to a greater aromaticity of pyrrole and thiophene relative to furan. 

The planar bond configuration of the nitrogen atom in pyrrole is usually explained in terms of aromaticity. The pyramidalization of the phosphorus and arsenic atoms in phosphole (130) and arsole (131) was taken to be the consequence of their much lower aromaticity relative to pyrrole [75JCS(P2)974] (see Table VIII). 

As a result of its reduced aromaticity, relative to pyrrole, furan undergoes [4 + 2] cycloaddition reactions much more readily. It combines as a diene with electron-poor dienophiles to yield Diels-Alder-type adducts. Maleic [(Z)-butenedioic acid] anhydride, for example, reacts at room temperature, and the only isolated adduct is the exo isomer (the more thermodynamically favoured adduct) (Scheme 6.27a). 

The definition of aromaticity conceived by Hiickel strictly applies to monocyclic ring systems, but indole, constructed from the fusion of benzene and pyrrole, behaves as an aromatic compound, like quinoline and isoquinoline. The ring fusion, however, affects the properties of both components. This is reflected in the valence bond description of indole, shown in Scheme 7.1, where one canonical representation shows electron density shared between N-1 and C-3 in the pyrrole unit (implying enamine character). Note that although other canonical forms can be drawn, where the lone-pair electrons are delocalized into the benzenoid ring, their energy content is relatively high and they are of limited importance. 

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