Pyrrole ring electronic density

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). 

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. 

In condensed heteroaromatic systems with a bridge-head pyrrolic nitrogen atom, tr-electron density is always shifted from the electron-rich six-membered ring (formally contains 7 Tr-electrons) towards the five-membered ring (formally has 6 Tr-electrons). As a result electrophiles are directed to carbon atoms of the latter. Thus, imidazo[ 1,2-a]pyridines (140) unsubstituted at C-3 almost always react with electrophiles at that position. 

H-5), 7.5-6.8 (unsaturated JS-H), 2.0 (NH) for (iBchl).2,14 The signal of a proton on the meso carbon attached to a pyrroline ring is located at 1 p.p.m. higher frequency than the others partly because of the increased electron density on the position and partly because of the loss of pyrrolic ring current effects. 

Homonuclear correlation spectroscopy (COSY) experiments (see Chapter 9) substantiate the theoretical predictions, based on molecular orbital calculation, of the pattern of spin delocalization in the 3e orbitals of low-spin Fe(III) complexes of unsymmetrically substituted tetraphenylporphyrins [46]. Furthermore, the correlations observed show that this n electron spin density distribution is differently modified by the electronic properties of a mono-orf/io-substituted derivative, depending on the distribution of the electronic effect over both sets of pyrrole rings or only over the immediately adjacent pyrrole rings [46]. No NOESY cross peaks are detectable, consistently with expectations of small NOEs for relatively small molecules and effective paramagnetic relaxation [47]. 

A phenyl group as a /3-substituent on the vinyl group apparently increases the electron density of the 5-carbon of the pyrrole ring, so Michael-type addition is favored. The fumarate ester 43a was obtained in 37% yield in the reaction of 42a with DMAD (83JOC2488). With a methyl group as a /8-substituent in 42b, a mixture of the fumarate ester 43b (37%) and the 3a,6-dihydroindole 44 (40%) was obtained (84MI1). 

A depending on the size of the lanthanide metals. Delocalization of electron density on four equivalent nitrogen atoms causes elongation of the Ln-N bonds at about 0.10-0.15 A compared to silylamides. The close proximity of the macrocyclic 7i-systems in sandwich complexes proved to be useful as structural and spectroscopic models for the bacteriochlorophyll [Mg(Bchl)]2, the special pair in the reaction center of bacterial photosynthesis [211,212]. The distance between the pyrrole rings in [Mg(Bchl)]2 is about 3 A. 

The reactivity sequence furan > selenophene > thiophene > benzene has also been observed in the nucleophilic substitutions of the halogenonitro derivatives of these rings.21,22 This shows that the observed trend does not depend on the effectiveness of lone-pair conjugation of the heteroatoms NH, O, Se, and S and the 77-electron density at the carbon atoms. It is interesting to note that a good correlation is observed between molecular ionization potentials (determined from electron impact measurements) and reactivity data in electrophilic substitution, in that higher reactivities correspond to lower ionization potentials182 pyrrole furan < selenophene < thiophene benzene (see Table VII). This is expected in view of a... 

Indole (2) undergoes electrophilic substitution preferentially at the b(C3)-position whereas pyrrole (1) reacts predominantly at the a(C2)-position [15]. The positional selectivity in these five-membered ring systems is well explained by the stability of the Wheland intermediates for electrophilic substitution. The intermediate cations from 3 (for indole, 2) and a (for pyrrole, 1) are the more stabilized. Pyrrole compounds can also participate in cycloaddition (Diels-Alder) reactions under certain conditions, such as Lewis acid catalysis, heating, or high pressure [15]. However, calculations of the frontier electron population for indole and pyrrole show that the HOMO of indole exhibits high electron density at the C3 while the HOMO of pyrrole is high at the C2 position [25-28] (Scheme 3). 

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