Pyrrole resonance

Unsymmetrically substituted dipyrromethanes are obtained from n-unsubstitued pyrroles and fl(-(bromomethyl)pyiToIes in hot acetic acid within a few minutes. These reaction conditions are relatively mild and the o-unsubstituted pyrrole may even bear an electron withdrawing carboxylic ester function. It is still sufficiently nucleophilic to substitute bromine or acetoxy groups on an a-pyrrolic methyl group. Hetero atoms in this position are extremely reactive leaving groups since the a-pyrrolylmethenium( = azafulvenium ) cation formed as an intermediate is highly resonance-stabilized. 

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). 

Pyrrole has a planar, pentagonal (C2 ) stmcture and is aromatic in that it has a sextet of electrons. It is isoelectronic with the cyclopentadienyl anion. The TT-electrons are delocalized throughout the ring system, thus pyrrole is best characterized as a resonance hybrid, with contributing stmctures (1 5). These stmctures explain its lack of basicity (which is less than that of pyridine), its unexpectedly high acidity, and its pronounced aromatic character. The resonance energy which has been estimated at about 100 kj/mol (23.9 kcal/mol) is intermediate between that of furan and thiophene, or about two-thirds that of benzene (5). 

Pyrrole is soluble in alcohol, benzene, and diethyl ether, but is only sparingly soluble in water and in aqueous alkaUes. It dissolves with decomposition in dilute acids. Pyrroles with substituents in the -position are usually less soluble in polar solvents than the corresponding a-substituted pyrroles. Pyrroles that have no substituent on nitrogen readily lose a proton to form the resonance-stabilized pyrrolyl anion, and alkaU metals react with it in hquid ammonia to form salts. However, pyrrole pK = ca 17.5) is a weaker acid than methanol (11). The acidity of the pyrrole hydrogen is gready increased by electron-withdrawing groups, eg, the pK of 2,5-dinitropyrrole [32602-96-3] is 3.6 (12,13). 

Hydroxypyrroles. Pyrroles with nitrogen-substituted side chains containing hydroxyl groups are best prepared by the Paal-Knorr cyclization. Pyrroles with hydroxyl groups on carbon side chains can be made by reduction of the appropriate carbonyl compound with hydrides, by Grignard synthesis, or by iasertion of ethylene oxide or formaldehyde. For example, pyrrole plus formaldehyde gives 2-hydroxymethylpyrrole [27472-36-2] (24). The hydroxymethylpyrroles do not act as normal primary alcohols because of resonance stabilization of carbonium ions formed by loss of water. 

Resonance energies of ca. 90, 182 and 330 kJ moF have been estimated for pyrrole, indole and carbazole respectively by comparing their protonation constants with those for selected model compounds (72C1(L)335, 72TL5019). 

In summary, all estimates of resonance energies indicate a decrease in aromaticity in the sequence benzene > thiophene > pyrrole > furan. Similar sequences are also found for the benzo[6] and dibenzo analogues. A somewhat different sequence is found for the benzo[c] fused heterocycles with isoindole > benzo[c]thiophene > benzo[c]furan. As would be anticipated, the resonance energies for the benzo[c] heterocycles are substantially lower than those for their benzo[6] isomers. 

In contrast to H shifts, C shifts cannot in general be used to distinguish between aromatic and heteroaromatic compounds on the one hand and alkenes on the other (Table 2.2). Cyclopropane carbon atoms stand out, however, by showing particularly small shifts in both the C and the H NMR spectra. By analogy with their proton resonances, the C chemical shifts of k electron-deficient heteroaromatics (pyridine type) are larger than those of k electron-rieh heteroaromatic rings (pyrrole type). 

The heteroaromatic compounds can be divided into two broad groups, called n-excessive and n-deficient, depending on whether the heteroatom acts as an electron donor or an electron acceptor. Furan, pyrrole, thiophene, and other heterocyclics incorporating an oxygen, nitrogen, or sulfur atom that contributes two n electrons are in the rr-exeessive group. This classification is suggested by resonance structures and confirmed by various MO methods. ... 

Examine pyrrole s highest-occupied molecular orbital (HOMO) to see if your can predict the most favorable protonation site. Which of the pyrrole s conjugate acids (N protonated, C2 proto noted, C3 proto noted pyrrole) is lowest in energy Examine electrostatic potential maps to see if the lowest-energy form is also that in which the positive charged is best delocalized. Rationalize your result using resonance arguments. What should be the favored substitution product ... 

The amino form is usually much more favored in the equilibrium between amino and imino forms than is the hydroxy form in the corresponding keto-enol equilibrium. Grab and XJtzinger suggest that in the case of a-amino- and a-hydroxy-pyrroles, structure 89 increases the mesomeric stabilization and thus offsets the loss of pyrrole resonance energy, but the increase due to structure 90 is not sufficient to offset this loss. Similar reasoning may apply to furans and... 

The regioselectivity observed in these reactions can be correlated with the resonance structure shown in Fig. 2. The reaction with electron-rich or electron-poor alkynes leads to intermediates which are the expected on the basis of polarity matching. In Fig. 2 is represented the reaction with an ynone leading to a metalacycle intermediate (formal [4C+2S] cycloadduct) which produces the final products after a reductive elimination and subsequent isomerisation. Also, these reactions can proceed under photochemical conditions. Thus, Campos, Rodriguez et al. reported the cycloaddition reactions of iminocarbene complexes and alkynes [57,58], alkenes [57] and heteroatom-containing double bonds to give 2Ff-pyrrole, 1-pyrroline and triazoline derivatives, respectively [59]. 

Pyrrole, C4H6N, is found to have a resonance energy of 0.98 v.e., despite the fact that the structure... 

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