Heterocycles electron-excessive aromatic

The acid-catalyzed ot7, o-acylation of /3-oxoalkyl derivatives of 7t-excess aromatic heterocycles known as the Dorofeenko-Dulenko-Krivun reaction affords condensed pyrylium derivatives which are convenient precursors of the corresponding pyridines <2001CHE1310>. By this approach (Scheme 14), carbazole 100 is converted into carba-zolo[3,2-f]pyrylium 101, a new ISrt-electron heteroaromatic system, and 101 is readily transformed into isomer 102 of 6-methylellipticine via an Sn(ANRORC) reaction using ammonia. The yields for these transformations were not reported. 

The TT-electron excess of the five-membered rings is accompanied by a high rr-donor character. The best measure of rr-donation is the value of first ionization potential, IP, which for all aromatic heterocycles with one heteroatom of pyrrole type reflects the energy of highest occupied rr-orbital. IP, values decrease in the sequence pyrrole > indole > carbazole furan > benzo[/ ]furan > dibenzofuran thiophene > benzo[/ ]thiophene (Section 2.3.3.9, Tables 21 and 23). Thus, the more extensive the rr-system, the stronger is its electron donor ability. Furan and thiophene possess almost equal rr-donation, which is considerably lower than that of pyrrole. 

Thiophene is a usefiil template for four-carbon homologation via reduction [9], as well as a bioisostere of the benzene ring and other heterocydes in medicinal chemistry. Thiophene is a n-electron-excessive heterocycle. It favors electrophilic substitution, which, similar to metalation, takes place preferably at the a-positions due to the electronegativity of the sulfiir atom [10]. In comparison to the oxygen atom in fiiran, the sulfiir atom in thiophene has lower electronegativity, so its lone pair electtons are more effectively incorporated into the aromatic system. The aromaticity of thiophene is in between that of benzene and fiiran. As a consequence, the difference in reactivity of a-halothiophenes and 3-halothiophenes is not as pronounced as that of the corresponding halofiirans. 

The role of heteroatoms in ground- and excited-state electronic distribution in saturated and aromatic heterocyclic compounds is easily demonstrated by a comparison of a number of heteroaromatic systems with their perhydro counterparts. In Jt-excessive heteroaromatic systems, because of their resonance structures, their dipole moments are less in the direction of the heteroatom than in the corresponding saturated heterocycles furan (1, 0.71 D) vs. tetrahydrofliran (2, 1.68 D), thiophene (3, 0.52 D) vs. tetrahydrothiophene (4, 1.87 D), and selenophene (5, 0.40 D) vs. tetrahydroselenophene (6, 1.97 D). In the case of pyrrole (7, 1.80 D), the dipole moment is reversed and is actually higher than that of pyrrolidine (8, 1.57 D) due to the acidic nature of the pyrrole ring (the N-H bond) In contrast, the dipole moment of n-deficient pyridine (9, 2.22 D) is higher than that of piperidine (10, 1.17 D). In all these compounds, with the exception of pyrrole (7), the direction of the dipole moment is from the ring towards the heteroatom [32-34]. 

Thiophene is aromatic. Its electronic structure follows from Fig. 5.2 (see p 53). Thiophene is a n-excessive heterocycle, i.e. the electron densitiy on each ring atom is greater than one. The value of the empirical resonance energy of thiophene is approximately 120 kJ moT the Dewar resonance energy is quoted as 27.2 kJ mol The aromaticity of thiophene is thus less than that of benzene but greater than that of furan. There are two possible explanations to account for the difference between thiophene and furan ... 

Pyrrole is aromatic (see Fig. 5.2, p 53). Like furan and thiophene, it belongs to the r-electron excessive heterocycles because the electron density on each ring atom is greater than one ... 

Heteroatoms in five-membered 7i-excessive heteroaromatic compounds are responsible for the chemical behaviour of the molecules as a whole. The heteroatoms not only give electrons to form an aromatic n-electron system but also determine the direction of the attack of electrophilic or nucleophilic agents. In fused 7i-excessive heterocycles containing two or more heteroatoms, the reactivity of compounds and their physical properties are substantially affected by both the mutual arrangement of the heteroatoms and the electronic effects associated with their nature. 

Pyrrole, with 6 7u-electrons, is an QlQcXron-excessive (also known as electron-r/c/ ) aromatic heterocycle because the electron density on each ring atoms is greater than one. Its lone pair electrons take part in the delocalization thus essential to pyrrole s aromaticity. Pyrrole s aromaticity is between furan and thiophene, which is in accordance with Pauling s electronegativity for O (3.5), N (3.0), and S (2.5) ... 

The reason why pyrrole is an QlQcixon-excessive aromatic heterocycle is because the electron density on each ring atom is greater than one. Pyrrole has a dipole moment of 1.55 D, similar to that of pyrrolidine in number although with opposite direction. (Here, the direction of the dipole moment vector is represented by an arrow and is properly defined so that the arrow is directed from the positive fractional charge to the negative fractional charge). 

Indole is classified as a 7c-excessive aromatic compound. It is isoelectronic with naphthalene, with the heterocyclic nitrogen atom donating twm of the ten 7t-electrons. 

Fully unsaturated azocines are 7r-equivalent heterocyclic analogs of cy-clooctatetraene. Addition of two electrons to the completely unsaturated azocine (34) can lead to a dianion 35 and removal of a proton from a dihy-droazocine (36) to the monoanion 37. Both the mono- and the dianions are lOTT-electron systems, corresponding to 7r-equivalent and 7r-excess analogs of cyclooctatetraenide [84CHEC-I(7)653], Aromatic dianions related to 35 have been fully characterized by and NMR (87TL2517). 

Heterocycles with conjugated jr-systems have a propensity to react by substitution, similarly to saturated hydrocarbons, rather than by addition, which is characteristic of most unsaturated hydrocarbons. This reflects the strong tendency to return to the initial electronic structure after a reaction. Electrophilic substitutions of heteroaromatic systems are the most common qualitative expression of their aromaticity. However, the presence of one or more electronegative heteroatoms disturbs the symmetry of aromatic rings pyridine-like heteroatoms (=N—, =N+R—, =0+—, and =S+—) decrease the availability of jr-electrons and the tendency toward electrophilic substitution, allowing for addition and/or nucleophilic substitution in yr-deficient heteroatoms , as classified by Albert.63 By contrast, pyrrole-like heteroatoms (—NR—, —O—, and — S—) in the jr-excessive heteroatoms induce the tendency toward electrophilic substitution (see Scheme 19). The quantitative expression of aromaticity in terms of chemical reactivity is difficult and is especially complicated by the interplay of thermodynamic and kinetic factors. Nevertheless, a number of chemical techniques have been applied which are discussed elsewhere.66... 

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