Aromaticity of pyrrole

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 nucleophilic nature of the ring means that pyrrole is attacked readily by electrophiles. Reaction with bromine requires no Lewis acid and leads to substitution (confirming the aromaticity of pyrrole) at all four free positions. 

An obvious consequence of this deiocaiization is the decreased basicity of the nitrogen atom and the increased acidity of the NH group. In fact, the pK of pyrrole acting as a base is about -4, and protonation occurs at carbon below pH -4. By contrast, the NH proton pK 16.5) can be removed by much weaker bases than those that can remove protons on normal secondary amines. The nucieophiiic nature of the ring means that pyrrole is attacked readily by electrophiles. Reaction with bromine requires no Lewis add and leads to substitution (confirming the aromaticity of pyrrole) at all four free positions. Contrast pyridine s reactivity with bromine (p. 731) it reacts just once, at nitrogen. 

Pyrroles, like fiirans, are also 1,3-dienes and one might suspect that the Diels-Alder reaction would occur as with furan. This suspicion is correct, but the aromaticity of pyrrole introduces complications. Such reactions are often slow, and aromaticity is sometimes regdned through a retro Diels-Alder reaction. With those hints, you should be able to tackle Problem 14.4. 

Despite the lone pair on nitrogen, pyrrole is a very weak base, because the lone pair is a part of the aromatic system. The p/Cj, of the cation formed by protonation of pyrrole, 12.20, is -3.8 the cation is strongly disfavored, as the aromaticity of pyrrole has been lost. However, pyrrole is relatively easy to deprotonate its p/Cj, is 17, comparable to that of cyclopentadiene at 16. The anion still has a full octet of electrons at nitrogen, and the aromatic system remains intact. 

Indoles are usually constructed from aromatic nitrogen compounds by formation of the pyrrole ring as has been the case for all of the synthetic methods discussed in the preceding chapters. Recently, methods for construction of the carbocyclic ring from pyrrole derivatives have received more attention. Scheme 8.1 illustrates some of the potential disconnections. In paths a and b, the syntheses involve construction of a mono-substituted pyrrole with a substituent at C2 or C3 which is capable of cyclization, usually by electrophilic substitution. Paths c and d involve Diels-Alder reactions of 2- or 3-vinyl-pyrroles. While such reactions lead to tetrahydro or dihydroindoles (the latter from acetylenic dienophiles) the adducts can be readily aromatized. Path e represents a category Iley cyclization based on 2 -I- 4 cycloadditions of pyrrole-2,3-quinodimcthane intermediates. 

In pyrrole on the other hand the unshared pair belonging to nitrogen must be added to the four tt electrons of the two double bonds m order to meet the six tt elec tron requirement As shown m Figure 11 166 the nitrogen of pyrrole is sp hybridized and the pair of electrons occupies a p orbital where both electrons can participate m the aromatic tt system... 

Iron Porphyrins. Porphyrias (15—17) are aromatic cycHc compouads that coasist of four pyrrole units linked at the a-positions by methine carbons. The extended TT-systems of these compounds give rise to intense absorption bands in the uv/vis region of the spectmm. The most intense absorption, which is called the Soret band, falls neat 400 nm and has 10. The TT-system is also responsible for the notable ring current effect observed in H-nmr spectra, the preference for planar conformations, the prevalence of electrophilic substitution reactions, and the redox chemistry of these compounds. Porphyrins obtained from natural sources have a variety of peripheral substituents and substitution patterns. Two important types of synthetic porphyrins are the meso-tetraaryl porphyrins, such as 5,10,15,20-tetraphenylporphine [917-23-7] (H2(TPP)) (7) and P-octaalkylporphyrins, such as 2,3,7,8,12,13,17,18-octaethylporphine [2683-82-1] (H2(OEP)) (8). Both types can be prepared by condensation of pyrroles and aldehydes (qv). 

In summary, most of the presently available criteria point to an order of decreasing aromaticity of benzene > thiophene > selenophene pyrrole > tellurophene > furan. 

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). 

The low basicity of pyrrole is a consequence of the loss of aromaticity which accompanies protonation on the ring nitrogen or on carbon 2 or carbon 3 of the ring. The thermodynamically most stable cation is the 2H-pyrrolium ion, and the p/sTa for protonation at C-2 has been recorded as -3.8 the corresponding pK values for protonation at C-3 and at nitrogen are -5.9 and ca. -10 (Scheme 7). 

Draw appropriate Lewis structures for pyrrole. How many K electrons does pyrrole have Is pyrrole aromatic Would you expect the three carbon-carbon bonds to be approximately the same length Explain. Examine the actual geometry of pyrrole. Are the bonds the same length ... 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

Because diacetylene is unstable, a stable diacetylene derivative, 1-methoxybut-l-en-3-yne (65CB98), is often employed in the synthesis of pyrroles. The reaction with ammonia proceeds under conditions of heterogeneous catalysis (a mixture of reagent vapors is passed through a catalyst-containing reactor heated to 150°C), approaching a yield of 50-70% but with primary aromatic amines, the yield drops to 20%. 

Pyrrole (two r s, one /) and imidazole are /ive-membered heterocycles, yet both have six tt electrons and are aromatic. In pyrrole, each of the four. sp2-hybridized carbons contributes one tt electron, and the sp2-hybridized nitrogen atom contributes the two from its lone pair, which occupies a p orbital (Figure 15.9). Imidazole, also shown in Figure 15.9, is an analog of pyrrole that has two nitrogen atoms in a five-membered, unsaturated ring. Both nitrogens are sp2-hybridized, but one is in a double bond and contributes only one electron to the aromatic tt system, while the other is not in a double bond and contributes two from its lone pair. 

---